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Psorilax:Ora |resolve psoriasi crema 100 ml

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Psorilax: prezzo, funziona, recensioni, opinioni, quanto costa

Una donna stressata in primo piano con una foto di un'eruzione cutanea.

Meno stress è il migliore

Lo stress è un fattore scatenante comune della psoriasi (una malattia che produce bagliori argentati, squamosi, secchi e ispessiti con macchie rossastre); tuttavia, i razzi della psoriasi causano anche stress. Lo stress aumenta l'infiammazione nel corpo. I composti infiammatori sono dannosi per i tessuti del corpo. Le donne sembrano particolarmente vulnerabili a sperimentare riacutizzazioni della psoriasi a causa dello stress. Le persone che hanno condizioni autoimmuni, come la psoriasi, sembrano avere sistemi immunitari che rispondono in modo eccessivo e rilasciano un'abbondanza di composti infiammatori.

Stress Busters

Il controllo dello stress è un modo per ridurre al minimo il rischio di futuri razzi della psoriasi. Esistono molti metodi per combattere lo stress.

  • La respirazione diaframmatica profonda coinvolge il cosiddetto sistema nervoso parasimpatico “riposo e digest”. Inspirare attraverso il naso, lentamente e profondamente dal diaframma. Trattieni il respiro e poi espira lentamente attraverso la bocca.
  • L'esercizio fisico migliora l'umore, migliora i livelli di energia e rilascia endorfine, sostanze chimiche di benessere associate alla riduzione del dolore. L'esercizio fisico regolare riduce l'ansia e migliora il sonno. Le donne che si esercitano vigorosamente e hanno meno probabilità di sviluppare la psoriasi rispetto alle donne che sono meno attive fisicamente.
  • Chiedi l'aiuto di un terapista o iscriviti a un programma di gestione dello stress per imparare a gestire lo stress in modo più efficace. Un terapista può utilizzare la terapia cognitivo comportamentale (CBT) per aiutarti a cambiare pensieri e comportamenti per mantenere bassi i livelli di stress.

Sia le allergie che la psoriasi sono dovute a disfunzione immunitaria ma non ci sono prove scientifiche che la psoriasi sia una reazione allergica.

Ottieni una gestione delle allergie

Allergie e Psoriasi

Sebbene sia le allergie che la psoriasi siano dovute a disfunzione immunitaria, non ci sono prove scientifiche che la psoriasi sia una reazione allergica. Alcune persone che hanno entrambe le condizioni riferiscono che i sintomi di allergia scatenano razzi della psoriasi. Le lesioni cutanee psoriasiche possono essere confuse con condizioni allergiche, ma i due processi patologici sono diversi.

Allergy Busters

Se hai allergie e psoriasi, adottare misure per controllare le allergie può aiutare a ridurre il rischio di flare della psoriasi.

  • Evitare allergeni noti è una strategia efficace per ridurre i sintomi. Ad esempio, se si è allergici agli acari della polvere, ridurre al minimo i mobili imbottiti, sostituire la moquette con pavimenti duri e polvere e vuoto frequentemente per ridurre l'esposizione.
  • Prendi i farmaci per le allergie come prescritto dal medico. L'assunzione di medicinali allergici nei momenti corretti e dosaggi corretti contribuirà a ridurre al minimo i sintomi allergici.
  • Tieni traccia dei tuoi sintomi in un diario. Se emergono sintomi nuovi o preoccupanti, tenere traccia di ciò che si mangia, dove si va e ciò a cui si è esposti può aiutare a rivelare schemi che possono essere utilizzati per regolare il trattamento.

Alcuni studi mostrano un legame tra bere alcolici pesanti e razzi della psoriasi.

Fai attenzione al consumo di alcol

Alcol e Psoriasi

Alcuni studi mostrano un legame tra bere pesante e razzi psoriasi. Sembra che gli uomini che bevono molto abbiano maggiori probabilità di soffrire di psoriasi rispetto agli uomini che non bevono alcolici. Il consumo di alcol influisce negativamente sul trattamento e riduce la probabilità di remissione. L'alcol può interagire con alcuni farmaci per la psoriasi. Chiedi al tuo medico se è sicuro per te consumare alcol se hai la psoriasi.

Suggerimenti per smettere di bere

Se stai cercando di ridurre o smettere di bere tutti insieme, la gestione dei trigger può aiutarti a raggiungere il tuo obiettivo. In generale, evita situazioni ad alto rischio in cui prevedi che sarà difficile evitare la tentazione. Se non riesci a evitare una situazione che ti preoccupa potresti essere innescato, metti in atto alcune strategie per aiutarti a rimanere in pista e farcela.

  • Distraiti chiamando o inviando un SMS a un amico o guardando un video divertente online. Fai una passeggiata o prenditi qualche minuto per praticare la respirazione profonda o la meditazione.
  • Rivedi i tuoi motivi per non voler bere. Scrivi i motivi su una carta che tieni nella borsetta o nel portafoglio per rivisitarli quando è necessario.
  • Parla con un amico fidato quando sei tentato di bere e discuti i motivi per cui stai cercando di astenermi.

L'aria fredda, le temperature secche e la luce solare ridotta contribuiscono ai razzi della psoriasi.

Proteggiti da tempo freddo o secco

Psoriasi invernale

L'aria fredda, le temperature secche e la luce solare ridotta contribuiscono a razzi della psoriasi in inverno. Combatti queste condizioni usando un umidificatore al chiuso. L'uso di idratanti pesanti aiuta a combattere la pelle secca e riduce il disagio causato dalla psoriasi invernale. Scegli idratanti e prodotti per la pelle che sono privi di profumo, ipoallergenici e formulati per le pelli sensibili.

Consigli per la cura della pelle invernale

La pelle ha bisogno di cure e attenzioni extra in inverno, sia che tu abbia la psoriasi o meno. Usa questi consigli per la cura della pelle invernale per mantenere la pelle sana quando fuori fa freddo e si secca.

  • Pelle pulita ed esfoliante: Usa detergenti delicati e senza sapone che non toglieranno l'umidità dalla pelle. Distendi delicatamente le cellule morte con un panno morbido o uno scrub esfoliante delicato per rivelare una pelle fresca e sana sotto.
  • Salta i bagni caldi e le docce: Anche se è allettante riscaldarsi in un bagno caldo o fare la doccia in una fredda giornata invernale, l'acqua calda in realtà toglie l'umidità dalla pelle. Fare il bagno o la doccia in acqua calda invece.
  • Aumenta la crema idratante: Potrebbe essere necessario passare a un idratante più pesante a base di olio in inverno per estinguere la pelle secca.
  • Vestire a strati e rimuovere prontamente gli indumenti bagnati: Stare seduti con indosso vestiti bagnati può irritare la pelle e causare rotture e piaghe. Rimuovere prontamente gli indumenti bagnati. E vestiti a strati in modo da poter rimuovere gli indumenti se diventi troppo caldo ed evita la sudorazione eccessiva.
  • Affidati al tuo umidificatore: Il tempo secco secca la pelle e può provocare crepe e prurito. Usa un umidificatore per rendere il tuo spazio abitativo meno arido. L'umidità aiuta a mantenere la pelle sana e inumidisce le mucose nella cavità nasale, il che può aiutare a ridurre il rischio di sinusite.

I tatuaggi sono associati a traumi cutanei che possono scatenare la psoriasi.

Ripensare l'inchiostro: tatuaggi

Tatuaggi e psoriasi

Potresti apprezzare l'aspetto dei tatuaggi, ma potrebbero non essere una buona idea se hai la psoriasi. Il piercing alla pelle e l'iniezione di colorante sotto la pelle sono associati a un trauma cutaneo che può scatenare la psoriasi. Alcune persone che hanno la psoriasi sviluppano nuove lesioni psoriasiche da 10 a 14 giorni dopo aver fatto un tatuaggio. Anche la pelle tatuata può essere infettata. Le infezioni della pelle sono anche potenziali fattori scatenanti della psoriasi.

Trauma cutaneo e psoriasi

Altri tipi di traumi della pelle oltre all'agopuntura possono scatenare razzi della psoriasi. Questi includono

  • tagli e graffi,
  • gravi scottature solari
  • punture di insetti e
  • piercing alla pelle.

I farmaci possono scatenare i razzi della psoriasi o peggiorare la situazione.

Valuta i tuoi farmaci

I farmaci possono scatenare la psoriasi?

Alcuni farmaci possono scatenare riacutizzazioni della psoriasi o peggiorare la psoriasi. Alcuni farmaci per controllare l'ipertensione, le malattie cardiache, l'artrite o i disturbi dell'umore possono influenzare la psoriasi. Non interrompere l'assunzione di un farmaco o regolare la dose di un farmaco senza parlare con il medico. Se hai dubbi sul fatto che un farmaco abbia un impatto negativo sulla tua psoriasi, discuti la situazione con il tuo medico.

Farmaci che scatenano la psoriasi

Esistono diverse classi di farmaci che possono scatenare i razzi della psoriasi. Parla con il tuo medico se sei preoccupato che uno qualsiasi dei seguenti farmaci possa esacerbare la tua psoriasi.

  • La chinidina è un farmaco per il cuore che può scatenare la psoriasi.
  • Inderal è un farmaco per la pressione sanguigna che può peggiorare la psoriasi in circa il 30% delle persone che lo assumono e hanno entrambe le condizioni.
  • I farmaci antimalarici tra cui clorochina, idrossiclorochina e chinacrina possono essere associati a un flare psoriasi circa 2-3 settimane dopo l'assunzione di questi farmaci.
  • L'indometacina è un farmaco antinfiammatorio prescritto per il trattamento dell'artrite. Può peggiorare la psoriasi in alcune persone.
  • Il litio è un farmaco prescritto per trattare la depressione maniacale e altri tipi di disturbi dell'umore. Può peggiorare la psoriasi in circa il 50% delle persone che la assumono.

Le infezioni attivano il sistema immunitario e possono scatenare una riacutizzazione della psoriasi.

Diagnosticare e trattare le infezioni

Psoriasi e Strep

Quando il sistema immunitario è impegnato a combattere un'infezione, la psoriasi può esplodere. L'infezione da streptococco o mal di gola, come è più comunemente noto, è un'infezione che è particolarmente legata alle riacutizzazioni della psoriasi. Lo streptococco è collegato a un tipo di psoriasi chiamata psoriasi guttata (tipo di lesione cutanea in cui compaiono squame sottili sopra lesioni rossastre simili a gocce). L'infezione da strep nei bambini può essere il fattore scatenante per l'insorgenza della psoriasi guttata. Se hai la psoriasi e hai una riacutizzazione, è una buona idea chiedere al tuo medico di valutare anche te per mal di gola.

Psoriasi e infezioni

Le infezioni attivano il sistema immunitario e possono scatenare una riacutizzazione della psoriasi. Le infezioni legate ai razzi della psoriasi comprendono

  • tonsillite,
  • infezione respiratoria,
  • mal d'orecchi e
  • bronchite.

Le riacutizzazioni della psoriasi tendono a calmarsi quando un'infezione concomitante viene trattata in modo efficace.

Proteggere e proteggere la pelle da lesioni come tagli e contusioni può aiutare a ridurre al minimo il rischio di riacutizzazioni della psoriasi.

Evita il trauma cutaneo: tagli e contusioni

Il fenomeno di Koebner

Le persone che soffrono di psoriasi possono sviluppare lesioni psoriasiche nel sito di una lesione cutanea. Questo fenomeno si chiama Koebner. Molto spesso, le persone sviluppano lesioni psoriasiche su aree cutanee ferite dove normalmente non si manifestano riacutizzazioni. Prestare particolare attenzione a proteggere la pelle da traumi evitabili e lesioni può aiutare a ridurre il rischio di riacutizzazioni della psoriasi.

Proteggi la tua pelle

Proteggere la pelle dalle lesioni può aiutare a ridurre al minimo il rischio di riacutizzazioni della psoriasi. Ci sono cose semplici che puoi fare per proteggere la tua pelle.

  • Indossare la protezione solare e stare lontano dal sole durante le ore di punta per evitare scottature.
  • Usa un repellente per insetti e indossa top a maniche lunghe e pantaloni lunghi per impedire agli insetti di mordere.
  • Taglia le unghie dei piedi dritte e evita di tagliare le unghie troppo corte.
  • Fai attenzione durante la rasatura o meglio ancora, usa un rasoio elettrico per ridurre al minimo intaccature e colpi che potrebbero scatenare la psoriasi.

Il fumo aumenta notevolmente il rischio di psoriasi e peggiora le condizioni.

I pericoli del fumo

Fumo e psoriasi

Il fumo aumenta notevolmente il rischio di psoriasi e peggiora la malattia. Gli studi hanno documentato che circa il 20% dei casi di psoriasi sono correlati al fumo. I composti nel fumo di sigaretta hanno un impatto negativo sul sistema immunitario e sulla crescita delle cellule della pelle per promuovere la psoriasi. Più sigarette una persona fuma al giorno, maggiore è il rischio di sviluppare la psoriasi.

Statistiche sul fumo e sulla psoriasi

Il fumo aumenta il rischio di sviluppare la psoriasi e aumenta la gravità della malattia. Ecco le statistiche riguardanti la psoriasi e il fumo.

  • Le persone che fumano hanno il doppio del rischio di sviluppare la psoriasi rispetto ai non fumatori.
  • I fumatori di sesso femminile hanno maggiori probabilità di sviluppare la psoriasi rispetto ai fumatori di sesso maschile.
  • Il fumo aumenta il rischio di un tipo di psoriasi chiamata pustolosi palmoplantare (psoriasi sulle mani e sui piedi).
  • Le donne che fumano 20 sigarette al giorno hanno un rischio 2,5 volte maggiore di sviluppare la psoriasi rispetto alle donne che non sono fumatori.
  • Gli uomini che fumano 20 sigarette al giorno hanno un rischio 1,7 volte maggiore di sviluppare la psoriasi rispetto agli uomini che non sono fumatori.
  • Circa il 78% delle persone che soffrono di remissione dalla psoriasi sono non fumatori. Solo il 22% delle persone che soffrono di remissione della psoriasi sono fumatori.

Fumare non fa bene a nessuno ma è particolarmente importante smettere se si ha la psoriasi.

I cambiamenti degli ormoni di solito precedono la psoriasi e possono influenzare la gravità.

Ormoni dell'equilibrio

Ormoni e psoriasi

Chiunque di qualsiasi età può avere la psoriasi, ma la condizione si verifica più comunemente nelle persone di età compresa tra 20 e 30 anni e in quelle di età superiore ai 50 anni. Si ritiene che i cambiamenti ormonali a quei tempi precedano l'insorgenza della psoriasi. Gli ormoni influenzano la gravità della condizione. I cambiamenti ormonali in gravidanza comportano una riduzione dei sintomi della psoriasi in oltre il 50% delle donne a 30 settimane di gestazione e un peggioramento dei sintomi in oltre il 20% delle donne.

Quali ormoni colpiscono la psoriasi?

Gli ormoni sessuali e la prolattina sono noti da tempo per influenzare lo sviluppo e la gravità della psoriasi, ma molti più ormoni sono stati implicati nel processo. Gli ormoni che hanno un effetto sulla psoriasi includono

  • estrogeni,
  • progesterone,
  • cortisolo,
  • epinefrina,
  • prolattina,
  • ormoni tiroidei,
  • leptina,
  • grelina e
  • insulina.

Se sospetti che gli ormoni fuori controllo contribuiscano ai sintomi della psoriasi, consulta il tuo medico o un endocrinologo per discutere delle tue preoccupazioni.

© 2005-2020 WebMD, LLC. Tutti i diritti riservati.

Psorilax:Bonus |crema tea tree just psoriasi

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Psorilax: prezzo, funziona, recensioni, opinioni, ingredienti

Psoriasi a placche

Fonte: Dr P Marazzi / Science Photo Library

La psoriasi a placche è caratterizzata da placche di ridimensionamento ipercheratotico eritematose ben definite di colore bianco argenteo che si verificano sulle superfici estensorie del corpo (ad es. Gomiti, ginocchia e parte bassa della schiena)

Tradizionalmente, la psoriasi era considerata solo un problema di pelle; tuttavia, ora è meglio descritto come una malattia complessa, multifattoriale e infiammatoria(1). Si pensa che la psoriasi colpisca tra il 2% e il 4% della popolazione nei paesi occidentali(2) e sebbene non pericoloso per la vita, è associato a una significativa compromissione della qualità della vita, che influenza il lavoro, le relazioni familiari e sessuali, nonché il benessere fisico e psicologico(3),(4). Inoltre, la natura visibile della condizione è stata segnalata dai pazienti come uno degli aspetti più difficili(5).

Entrambi i sessi sono ugualmente colpiti e, per la maggior parte dei pazienti (75%), la psoriasi si presenta per la prima volta tra i 15 e i 25 anni, mentre il resto delle persone colpite presenta sintomi tra i 55 e i 60 anni(6).

Esistono diverse forme di psoriasi (vedi tabella 1 e fotoguida 1), ma la più comune – che rappresenta fino al 90% di tutti i casi – è la psoriasi a placche cronica(7). Questo articolo si concentrerà sulla gestione dei pazienti adulti con psoriasi a placche nelle cure primarie, ma non discuterà dell'uso di speciali – coperti in pubblicazioni della British Association of Dermatologists – o di una discussione sui trattamenti forniti ai pazienti in cure secondarie.

Tabella 1: diversi tipi di psoriasi e loro aspetto e trattamento clinici
Tipo di psoriasi Aspetto clinico Trattamento
Psoriasi guttata In genere si presenta come piccole (1mm-10mm) placche ovali, squamose, di colore rosso-rosa su tutto il corpo. Più comune nei bambini e nei giovani, ma può verificarsi negli adulti ed è spesso preceduto da un'infezione alla gola da streptococco Sebbene la condizione possa risolversi senza trattamento, la terapia ultravioletta (UV) viene spesso utilizzata da due a tre volte a settimana per un massimo di otto settimane
Psoriasi pustolosa Caratterizzato da pustole bianche circondate da pelle infiammata. Spesso visto negli adulti; può essere localizzato (mani / palmi) o può coprire la maggior parte del corpo (psoriasi pustolosa generalizzata). I pazienti sviluppano pelle infiammata e in poche ore sviluppano pustole che possono fondersi per formare laghi di pus La psoriasi pustolosa generalizzata è un'emergenza medica e la morte può verificarsi per insufficienza cardiorespiratoria. La gestione secondaria prevede la prevenzione della perdita di liquidi, la stabilizzazione della temperatura corporea e la correzione dell'equilibrio elettrolitico
Psoriasi inversa o flessionale Colpisce le regioni intergiganti del corpo (axilla, fessura natale, regione genitale). L'aspetto tipico può essere descritto come rosso brillante, lesioni ben definite senza scala aderente Steroidi topici di lieve potenza spesso associati a un agente antifungino, a causa del potenziale di infezioni fungine coesistenti. Possono anche essere usati analoghi della vitamina D come il calcitriolo. Tuttavia, il patch test di una piccola area della pelle è utile per via del potenziale irritazione
Psoriasi pustolosa palmoplantare Presenta una serie di pustole sterili che si verificano sulle mani (sui palmi delle mani) e sulla pianta dei piedi Sono state utilizzate varie opzioni di trattamento, tra cui steroidi topici, catrame di carbone, acitretina e fototerapia
Psoriasi eritrodermica Un rossore generalizzato e spargimento della pelle, può essere descritto come simile a una pelle bruciata. La condizione può verificarsi in modo acuto o svilupparsi nell'arco di pochi giorni o addirittura settimane Una condizione potenzialmente pericolosa per la vita e richiede il ricovero in ospedale. Il trattamento prevede un agente psoriasico sistemico, combinato con emollienti, steroidi topici e correzione degli squilibri fluidi

Fotoguida che mostra psoriasi guttata, flessibile, eritrodermica, palmoplantare e pustolosa

Fotoguida 1: diversi tipi di psoriasi

Fonte: Science Photo Library

1. Psoriasi guttata: Piccole placche ovali (1–10 mm), squamose, di colore da rosso a rosa su tutto il corpo. Più comune nei bambini e nei giovani, ma può verificarsi negli adulti ed è spesso preceduto da un'infezione alla gola da streptococco.
2. Psoriasi flessibile sotto il seno: Lesioni rosse lucide e ben definite senza scala aderente, interessano le regioni intergiganti del corpo.
3. Psoriasi eritrodermica: Rossori e spargimento generalizzati della pelle possono essere descritti come pelle bruciata.
4. Psoriasi palmoplantare: Serie di pustole sterili che si verificano sulle mani (palmi) e sulla pianta dei piedi.
5. Psoriasi pustolosa: Caratterizzato da pustole bianche circondate da pelle infiammata. Spesso visto negli adulti; può essere localizzato (mani / palmi) o può coprire la maggior parte del corpo (psoriasi pustolosa generalizzata). I pazienti sviluppano pelle infiammata e, in poche ore, le pustole possono fondersi per formare laghi di pus

fisiopatologia

La causa precisa della psoriasi rimane poco chiara ma è probabile che sia responsabile una combinazione di fattori genetici, ambientali e immunologici. Prima degli anni '80, si credeva che la psoriasi fosse solo il risultato della disregolazione dei cheratinociti, che porta all'iper proliferazione di queste cellule nell'epidermide. Il lavoro successivo ha suggerito che la psoriasi era una malattia mediata dalle cellule T e l'importante ruolo della citochina pro-infiammatoria, il fattore di necrosi tumorale alfa (TNF-α), nella psoriasi è stato illustrato in uno studio usando l'agente anti-TNF-α, etanercept , in pazienti con artrite psoriasica. Dei 19 pazienti nel gruppo etanercept che avevano la psoriasi, 5 pazienti hanno ottenuto un miglioramento significativo nella loro psoriasi, rispetto a nessuno nel gruppo placebo(8). Il lavoro successivo ha dimostrato che altre interleuchine (IL), come IL23 e IL17A, hanno un ruolo importante nella malattia, sebbene non sia ancora stato spiegato esattamente come questi interagiscano per causare la psoriasi(9).

Diagnosi

Sintomi

Clinicamente, la psoriasi a placche è caratterizzata da placche di ridimensionamento ipercheratotiche eritematose, bianche argentee ben definite che si verificano sulle superfici estensorie del corpo (ad esempio gomiti, ginocchia e parte bassa della schiena), ma la psoriasi colpisce anche il cuoio capelluto (vedi Fotoguida 2). Molti pazienti sperimentano anche cambiamenti alle unghie, tra cui una crescita anormale della lamina ungueale che porta a una corrosione caratteristica, un accumulo di materiale cheratinoso sotto l'unghia (ipercheratosi subunguale) e onicolisi (separazione dell'unghia dal suo letto) (vedi Fotoguida 2) .

Fotoguida che mostra la psoriasi del cuoio capelluto e delle unghie

Fotoguida 2: Psoriasi del cuoio capelluto e delle unghie

Fonte: Science Photo Library

A. Psoriasi del cuoio capelluto: Placche di ridimensionamento ipercheratotiche eritematose ben definite di colore bianco argenteo.
Psoriasi delle unghie: Crescita anormale della lamina ungueale che porta a una caratteristica corrosione, un accumulo di materiale cheratinoso sotto l'unghia (ipercheratosi subunguale) e onicolisi (separazione dell'unghia dal suo letto)

La psoriasi si verifica, anche se meno comunemente, nei bambini, dove può essere diagnosticata erroneamente come eczema atopico, poiché il ridimensionamento è meno prominente e le lesioni spesso colpiscono il viso.

Comorbilità e fattori di rischio comuni

Diversi fattori legati allo stile di vita sembrano associati alla psoriasi. Uno studio caso-controllo italiano ha scoperto che il fumo di sigaretta, l'indice di massa corporea e lo stress sembravano essere correlati in modo indipendente con la psoriasi(10). Altri studi hanno dimostrato un'associazione tra psoriasi e obesità(11), consumo di alcool(12) e inattività fisica(13). Inoltre, ci sono prove che suggeriscono che la modifica dello stile di vita, come la perdita di peso(14) e aumento dell'attività fisica(15), sembrano ridurre la gravità della malattia. Alcune prove indicano un potenziale aumento del rischio di malattie cardiovascolari data una maggiore incidenza di sindrome metabolica nei pazienti con psoriasi(16). Tuttavia, una revisione di 14 studi di coorte ha rilevato che, sebbene vi sia un maggior rischio di malattie cardiovascolari, ciò è stato significativo solo per i pazienti con malattia grave (definiti come quelli che richiedono terapia sistemica o ricovero ospedaliero)(17).

Una delle comorbilità più frequenti è l'artrite psoriasica (PsA), una condizione infiammatoria cronica, degenerativa associata a malattia articolare progressiva(18),(19). In questo caso, il rilevamento precoce può aiutare a fermare l'ulteriore sviluppo. Lo screening per PsA può essere ottenuto utilizzando lo strumento di screening epidemiologico della psoriasi (PEST), che è facile e veloce da completare per i pazienti e ha una sensibilità del 97% e una specificità del 79%(20).

La diagnosi formale di PsA richiede una valutazione da parte di un reumatologo e, secondo l'Istituto nazionale per l'eccellenza nella salute e nella cura (NICE), l'organismo di valutazione delle tecnologie sanitarie, fino al 30% delle persone con psoriasi ha la PsA(21). La guida di NICE raccomanda agli operatori sanitari di offrire una valutazione annuale della psa alle persone con qualsiasi tipo di psoriasi e che se si sospetta la psa, il paziente deve essere indirizzato a un reumatologo per la valutazione e la consulenza sulla pianificazione della propria assistenza(22).

Inoltre, a causa della natura molto visibile della malattia, i pazienti spesso avvertono stress e ansia, che possono portare alla depressione in circa il 28% -67% dei pazienti(23).

Valutare la gravità della malattia

La diagnosi di psoriasi a placche si basa sui sintomi clinici e sulla considerazione di una storia familiare della malattia. Al contrario, non esiste una definizione universalmente accettata di gravità della malattia. Secondo la National Psoriasis Foundation negli Stati Uniti, la gravità può essere definita in termini di superficie corporea totale (BSA) interessata(24). La superficie di una sola mano (ovvero palmo piatto e cinque dita) della persona interessata, rappresenta circa l'1% della pelle totale dell'individuo. Sulla base di questa misura, la psoriasi lieve colpisce meno del 3% di BSA, moderata tra il 3% e il 10% di BSA e grave oltre il 10% di BSA(24).

Una delle misure più complete della gravità della malattia impiegata negli studi clinici è l'area della psoriasi e l'indice di gravità (PASI). Ciò valuta la gravità della malattia in quattro regioni corporee separate e i valori sommati in modo che i punteggi PASI siano compresi tra 0 e 72, con punteggi più alti che riflettono una maggiore gravità della malattia(25). Sono disponibili numerosi calcolatori utili per aiutare a calcolare i punteggi PASI (vedere il riquadro “Risorse utili” di seguito).

NICE utilizza lo strumento PASI come criterio qualificante per il trattamento, in modo tale che meno di 10 rappresentano una malattia lieve, maggiore di 10 ma meno di 20 rappresentano una malattia moderata e chiunque abbia un punteggio superiore a 20 ha una malattia grave(22). Inoltre, negli studi viene talvolta segnalata una valutazione globale del medico o del paziente della gravità della malattia da chiara a grave.

Mentre i punteggi PASI rappresentano una misura più completa della gravità della malattia rispetto alla BSA, nessuno dei due strumenti considera l'impatto sulla qualità della vita. Negli ultimi anni, la gravità è stata ridefinita da un gruppo di consenso europeo, che incorpora BSA, PASI e qualità della vita, misurata utilizzando l'indice di qualità della vita dermatologica (DLQI). La gravità è dicotomizzata in lieve o da moderata a grave. La psoriasi lieve è definita quando tutte e tre le misure hanno un valore inferiore a dieci e da moderato a grave dove tutte e tre le misure sono maggiori di dieci(26).

Gestione della psoriasi nelle cure primarie

Fortunatamente, la maggior parte dei pazienti con psoriasi a placche (circa l'80%) ha una malattia da lieve a moderata che può essere trattata nelle cure primarie con terapie topiche(27). I pazienti con patologie più diffuse sarebbero normalmente indirizzati e gestiti in cure secondarie con una gamma più ampia di trattamenti tra cui la terapia ultravioletta (UV), i farmaci antireumatici modificanti la malattia (DMARD) o persino gli agenti biologici in quelli con la malattia più grave.

Poiché al momento non esiste una cura per la psoriasi e la condizione segue uno schema di remissione recidivante, è importante valutare l'efficacia relativa dei trattamenti per garantire che i pazienti ottengano una risposta soddisfacente e rimangano in remissione il più a lungo possibile. Esistono numerosi agenti terapeutici topici disponibili e nella Tabella 2 viene fornito un riepilogo di questi agenti, il loro inizio d'azione e i principali effetti avversi.

Le più recenti revisioni sistematiche delle terapie topiche per la psoriasi sono una revisione Cochrane con ricerche di dati fino ad agosto 2012(28) e la revisione di NICE condotta in un periodo di tempo simile (fino a marzo 2012)(21), che ha portato a raccomandazioni terapeutiche descritte in questo articolo.

Tabella 2: Riepilogo dei principali trattamenti topici autorizzati per l'uso della psoriasi
Classe di droga Modalità di azione / utilizzo Insorgenza dell'effetto clinico (settimane) Effetti avversi più comuni
Adattato da Nast et al. 2012(29)
Steroidi topici Principalmente effetti anti-infiammatori. Gli steroidi potenti sono raccomandati per il tronco e gli arti, mentre gli agenti di potenza lieve sono riservati per l'uso sul viso e nelle flessioni. Applicato una o due volte al giorno utilizzando l'unità di punta delle dita come guida (copre un'area di circa una sola mano) e continua per un massimo di quattro settimane. Quando si applica a una placca, utilizzare un movimento circolare per coprire uniformemente, lasciando uno strato sottile visibile sulla placca 1-2 Bruciore o bruciore nel sito di applicazione. Può peggiorare le condizioni esistenti come l'acne o la rosacea
Analoghi della vitamina D. Non chiaro, ma si ritiene che comporti la soppressione delle citochine pro-infiammatorie e l'inibizione della proliferazione dei cheratinociti e una maggiore differenziazione dei cheratinociti. Generalmente utilizzato sul tronco o sugli arti, sebbene possa essere utilizzato anche in flessioni, ma generalmente troppo irritante per il viso. Applicare uno strato sottile sulle placche, una o due volte al giorno per un massimo di otto settimane 1-2 Irritazione cutanea come eritema, prurito e bruciore
Dithranol Soppressione della proliferazione cellulare di cheratinociti, citochine proinfiammatorie. Normalmente utilizzato come “regime di contatto corto”, a partire da una bassa resistenza (0,1%), applicando una piccola quantità sulla placca fino a completo assorbimento. Se tollerato, la forza può essere aumentata fino a quattro settimane alla massima resistenza tollerata. Il trattamento viene applicato tra 30 minuti e 60 minuti, quindi lavato via. Il miglioramento può richiedere fino a sei settimane. Tuttavia, può essere lasciato durante la notte, se necessario 2-3 Bruciore e gli occhi nella pelle. In pratica, è possibile ridurre l'irritazione per la pelle normale coprendo la pelle circostante con paraffina morbida bianca
Catrame di carbone Ancora poco chiaro ma ritenuto antiproliferativo / antinfiammatorio. Applicato come strato sottile alle placche due o tre volte al giorno 4-8 Minimo ma i pazienti possono provare irritazione cutanea e persino fotosensibilità. A molti pazienti non piace l'odore del catrame di carbone
Tazarotene Colpisce la proliferazione epidermica e la differenziazione agendo sui recettori dei retinoidi nella pelle. Applicato come strato sottile la sera per un massimo di tre mesi 1-2 Prurito, bruciore, eritema nel sito di applicazione e irritazione

trattamenti

emollienti

Sebbene generalmente non coperti dalle linee guida cliniche, gli emollienti hanno potenzialmente un ruolo aggiuntivo importante nella psoriasi, contribuendo ad ammorbidire e idratare lo strato corneo, migliorare la desquamazione (spargimento) della pelle ipercheratotica e fornire sollievo al prurito. C'è anche un suggerimento che gli emollienti potrebbero migliorare la penetrazione di altri trattamenti topici per la psoriasi. Nonostante il loro uso diffuso nella psoriasi e a Formulario nazionale britannico (BNF) raccomandazione che questi agenti potrebbero essere l'unico trattamento necessario nella psoriasi lieve, mancano dati attendibili sull'efficacia degli emollienti nella psoriasi, sebbene alcune prove suggeriscano che i prodotti contenenti urea o acido salicilico possano essere di beneficio(30).

Gli emollienti dovrebbero essere usati quotidianamente per aiutare a ridurre la pelle secca, ruvida, squamosa e squamosa. Possono essere applicati circa 30 minuti prima di qualsiasi trattamento attivo e devono essere usati come sostituti del sapone nel bagno o nella doccia. I pazienti devono essere informati che dopo la doccia o il bagno devono idratare tutto il corpo, nonché idratare eventuali aree secche o pruriginose della pelle o della psoriasi durante il giorno. I pazienti devono evitare di graffiare o raccogliere placche di psoriasi.

I farmacisti e gli operatori sanitari dovrebbero avvertire i pazienti che alcuni emollienti a base di paraffina rappresentano un rischio di incendio.

Terapia di combinazione

Ad oggi, l'unica terapia topica di combinazione commerciale è il calcipotriolo (un analogo della vitamina D) e il potente steroide topico, il betametasone. Il prodotto era originariamente disponibile solo come unguento ma ora è anche disponibile come gel, applicato da solo o tramite un dispositivo applicatore e una formulazione in schiuma. Numerose revisioni sistematiche hanno valutato l'efficacia della terapia di combinazione, con i dati più recenti inclusi fino ad aprile 2015(31). Questa revisione sistematica ha concluso che la terapia di combinazione era più efficace di uno dei componenti utilizzati da soli. Questa conclusione è stata anche rispecchiata nella recensione di Cochrane(28). Tuttavia, al contrario, NICE ha raccomandato di utilizzare i due componenti (calcipotriolo e betametasone) insieme, anche se separatamente, uno al mattino e uno alla sera(21) (a causa dell'elevato costo del prodotto combinato), ma i membri del gruppo di sviluppo delle linee guida per la psoriasi NICE sembravano accettare in una successiva pubblicazione che l'applicazione giornaliera del prodotto combinato era efficace quanto l'uso di uno dei due agenti separatamente(32).

Linee guida

Nel 2012, NICE ha pubblicato una linea guida per la valutazione e la gestione della psoriasi a placche. Tuttavia, altre linee guida prodotte nel Regno Unito non sono coerenti con i consigli di NICE, che sono potenzialmente fonte di confusione per gli operatori sanitari.

Come terapia iniziale, NICE ha raccomandato ai professionisti di offrire un potente corticosteroide applicato una volta al giorno, più vitamina D o un analogo della vitamina D applicato una volta al giorno (applicato separatamente, uno al mattino e l'altro alla sera) per un massimo di quattro settimane come iniziale trattamento per adulti con psoriasi del tronco o degli arti(22).

Inoltre, dati i potenti rischi dell'uso di potenti steroidi topici a lungo termine, la linea guida consiglia di rivedere i pazienti dopo quattro settimane di trattamento. Se la combinazione sembra essere efficace, lo steroide topico non deve essere usato nello stesso sito per più di otto settimane e il trattamento può essere continuato con l'analogo della vitamina D, consentendo un intervallo di “settimana senza steroidi” di quattro settimane.

La guida della Scottish Intercollegiate Guidelines Network (SIGN) è leggermente diversa e afferma che, per il trattamento iniziale, si raccomanda l'uso intermittente a breve termine di un corticosteroide topico potente o un corticosteroide potente combinato più unguento di calcipotriolo per ottenere un rapido miglioramento della psoriasi a placche(33).

Il consiglio della Primary Dermatology Society si allinea più con il SIGN piuttosto che con NICE, e afferma che molti medici generici e medici con un interesse speciale usano i prodotti di combinazione di calcipotriolo e betametasone di prima linea per incoraggiare un rapido miglioramento e quindi l'adesione alla psoriasi a placche cronica. La consulenza pertanto differisce dalle linee guida della psoriasi NICE che suggeriscono di iniziare con i suoi singoli componenti(34).

Quest'ultima raccomandazione ha chiaramente preso la strada nelle cure primarie. I dati di prescrizione del 2016 per Inghilterra e Galles mostrano che il 55% di tutti i trattamenti topici per la psoriasi emessi erano per le varie formulazioni del prodotto combinato (ad es. Gel, unguento e schiuma)(35).

Psoriasi del cuoio capelluto

Il coinvolgimento del cuoio capelluto si verifica fino al 79% dei pazienti con psoriasi del tronco o degli arti ed è spesso la prima area a mostrare segni della malattia(36). Clinicamente, le lesioni del cuoio capelluto sono placche ispessite, ben delimitate, infiammate, ridimensionanti che sono spesso pruriginose (vedi Fotoguida 2). Esistono diverse opzioni di trattamento per la psoriasi del cuoio capelluto, tra cui una gamma di shampoo da banco, che contengono catrame di carbone e / o acido salicilico, ai prodotti da prescrizione basati su steroidi topici e analoghi della vitamina D. Tuttavia, le prove sull'efficacia di questi trattamenti sono limitate.

In una recente revisione delle prove, che coinvolge l'analisi di 59 studi randomizzati con oltre 11.500 pazienti, una revisione di Cochrane ha concluso che la combinazione di un potente steroide topico e un analogo della vitamina D era più efficace di uno steroide da solo, sebbene il beneficio clinico era discutibile. Inoltre, gli autori non sono stati in grado di valutare l'efficacia di altri agenti topici come catrame, acido salicilico o dithranol(37).

Data la mancanza di dati di efficacia su shampoo da banco contenenti catrame o acido salicilico, sarebbe prudente per i farmacisti indirizzare i pazienti con psoriasi del cuoio capelluto al proprio medico di famiglia a meno che non abbiano una malattia molto lieve, nel qual caso gli shampoo possono essere di qualche beneficio .

Aderenza al trattamento

L'adesione ai regimi topici nella psoriasi è generalmente scarsa. Ad esempio, uno studio di Storm et al. ha riscontrato che il 44% dei pazienti non è riuscito a riscattare la prescrizione iniziale(38), mentre un altro studio di Richards et al. ha riscontrato che il 39% non era conforme al regime terapeutico raccomandato(39). Una migliore comprensione dei fattori associati all'aderenza può aiutare i farmacisti e altri operatori sanitari a supportare i pazienti per facilitare una migliore aderenza. Tuttavia, le prove fornite dalle recensioni della letteratura suggeriscono che l'aderenza è un problema complesso. Ad esempio, una recensione di Devaux et al trovato che i fattori più frequenti associati alla ridotta aderenza erano la bassa efficacia del trattamento, il tempo richiesto per l'applicazione e la ridotta accettabilità cosmetica della formulazione(40). Tuttavia, una successiva recensione di Thorneloe et al. ha concluso che le prove attuali rendono difficile accertare i più importanti determinanti dell'adesione(41). Infine, una recente recensione di Belinchon et al. ha suggerito che l'inclusione dei riferimenti dei pazienti nel processo decisionale del trattamento può contribuire a migliorare il trattamento, la soddisfazione, l'adesione e, in definitiva, i risultati clinici, sebbene non vi siano prove dirette a supporto di questo consiglio(42).

Un potenziale problema con la promozione di una maggiore aderenza, come identificato nella recensione di Thorneloe et al., è che quando i pazienti diventano esperti nella gestione delle loro condizioni, possono modificare il regime terapeutico per adattarsi a se stessi in modo che, sebbene la gravità della malattia possa non essere migliorata in modo ottimale, la strategia può migliorare la loro qualità di vita(41).

Come i farmacisti possono aiutare i pazienti con psoriasi

Studi qualitativi in ​​quei pazienti affetti da psoriasi hanno rivelato un uso spesso errato e incoerente di terapie topiche, un desiderio di consigli sull'uso corretto di terapie topiche (che di solito è assente nelle consultazioni) e una percezione che gli operatori sanitari non dispongono di conoscenze e competenze sufficienti di psoriasi(43),(44),(45). Di conseguenza, i pazienti spesso gestiscono in modo subottimale le loro condizioni e in isolamento dagli operatori sanitari a causa dell'assenza di consigli adeguati sui trattamenti. Questi studi illustrano chiaramente la necessità di informazioni, educazione e supporto più efficaci basati sulla comunità per i pazienti con psoriasi. Ci sono alcune prove che suggeriscono che l'educazione aggiuntiva del paziente per quelli con problemi della pelle come l'eczema atopico, porta a miglioramenti negli esiti della malattia(46), sebbene si sia concluso che gli interventi educativi per i pazienti con psoriasi impiegati negli studi clinici hanno avuto un successo limitato rispetto al miglioramento della gravità della malattia e della qualità della vita(47).

In un recente studio che ha esplorato l'impatto educativo dei consigli dei farmacisti sui pazienti con psoriasi, è stato riscontrato che i loro consigli e il loro supporto hanno portato a miglioramenti significativi nella comprensione dei pazienti delle loro condizioni, gravità della malattia e qualità della vita(48). Nello studio, i farmacisti hanno utilizzato uno strumento validato per valutare la conoscenza e la comprensione dei pazienti della loro psoriasi e della gravità della malattia e della qualità della vita autovalutata dai pazienti(49). I farmacisti hanno tenuto una consultazione iniziale e un appuntamento di follow-up sei settimane dopo, a quel punto tutte le misure di esito erano migliorate significativamente. Nelle interviste di follow-up di pazienti e farmacisti, entrambe le parti hanno concordato che l'intervento era di valore e i farmacisti si sono percepiti come membri importanti del team sanitario primario che si occupava di persone con psoriasi(50). Tuttavia, sono necessari ulteriori lavori per esplorare in modo più dettagliato il potenziale impatto dei consigli dei farmacisti sugli esiti della malattia nei soggetti con psoriasi.

Il riquadro 1 fornisce alcuni utili punti di consulenza che i farmacisti possono trasmettere ai pazienti con psoriasi.

Riquadro 1: punti di consulenza che i farmacisti possono trasmettere ai pazienti con psoriasi

  • Trova un emolliente o una gamma di prodotti emollienti per il lavaggio e l'idratazione che ti piacciono e che ti soddisfano, e usali ogni giorno;
  • Idrata tutto il corpo (comprese le aree della psoriasi) ogni giorno usando tratti lunghi, lisci e rilassanti (nella direzione della crescita dei capelli);
  • Porta con te una piccola quantità di crema idratante e applicala su placche asciutte e pruriginose durante il giorno;
  • Evitare di graffiare e raccogliere;
  • Lasciare circa 20-30 minuti tra i trattamenti topici emollienti e quelli della psoriasi, per aiutare l'efficacia di ciascuno;
  • Perseverare con i trattamenti topici della psoriasi per almeno un mese – la maggior parte impiega circa quattro settimane per iniziare a lavorare;
  • Ricorda che la scala scomparirà per prima e che la psoriasi potrebbe apparire rossa – questo è normale e continuando con il trattamento si avranno aree rosa, che gradualmente svaniranno al normale colore della pelle;
  • Se hai la psoriasi del cuoio capelluto, ridimensiona il cuoio capelluto prima di applicare trattamenti topici. Ricorda di separare i capelli e trattare il cuoio capelluto;
  • Elaborare una buona routine individuale – gli emollienti dovrebbero essere usati quotidianamente e i trattamenti di psoriasi solo quando le condizioni sono in fiamme;
  • Una volta che la pelle diventa piatta, i trattamenti attivi possono essere interrotti, anche se è necessario continuare con gli emollienti.

Dieta e psoriasi

I pazienti possono chiedere ai farmacisti il ​​ruolo della dieta nella psoriasi e se ci sono alimenti specifici che dovrebbero essere consumati o evitati. Esistono prove del fatto che il consumo di oli di pesce omega-3 può migliorare la gravità della malattia e che l'integrazione con vitamina D orale potrebbe aiutare, sebbene l'evidenza degli studi sia meno solida(51).

La Royal Pharmaceutical Society, nel suo rapporto “Migliorare l'assistenza alle persone con condizioni a lungo termine” , suggerisce che i farmacisti potrebbero aiutare i pazienti con condizioni a lungo termine e assistere quelli con la psoriasi offre l'opportunità di abbracciare quella visione(52). Sebbene al momento abbia una portata limitata, l'evidenza esistente offre alcune indicazioni su come i farmacisti potrebbero dare un importante contributo alla cura delle persone con psoriasi.

Informativa finanziaria e sui conflitti di interesse:

L'autore era un membro del gruppo NICE che ha sviluppato le linee guida per la psoriasi e ha ricevuto borse di ricerca e contributi per gli oratori da Leo Pharma, Mylan e Galderma. Nessuna assistenza scritta è stata utilizzata nella produzione di questo manoscritto.

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Psorilax:Grande |tacrolimus crema psoriasi

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Psorilax: prezzo, funziona, recensioni, opinioni, quanto costa

Con quasi tutti i nuovi marchi di prodotti per la cura della pelle sul mercato che usano parole come “pulito”, “naturale” e “non tossico”, è difficile determinare su quali prodotti dovresti spendere i tuoi soldi e quali sono i migliori per te e la tua pelle. Personalmente seguo una routine di cura della pelle pulita e naturale, perché dopo aver scoperto che ciò che metti sul tuo viso entra nel tuo flusso sanguigno, preferisco non pasticciare con le tossine.

Ho anche una pelle mista abbastanza resistente e non ho mai sofferto immensamente con acne, eczema o psoriasi, e quindi non ho dovuto ricorrere a ingredienti più duri e potenti che potrebbero non essere naturali. E mentre io non sono assolutamente un dermatologo o esperto di cura della pelle, come un editore di bellezza che gioca con Un sacco di nuovi prodotti, so cosa funziona per la mia pelle. Se stai cercando alcuni nuovi consigli sui prodotti o anche una nuova routine di cura della pelle naturale e hai la pelle mista, sei nel posto giusto.

Ma prima di entrare nella mia personale routine di cura della pelle naturale, voglio mettere le cose in chiaro con alcuni dei termini che ho menzionato sopra. Così, sono andato a Hillary Peterson, fondatore di True Botanicals, una linea di cura della pelle certificata MADE SAFE che utilizza solo gli ingredienti più sicuri e puliti presenti in natura. Ecco cosa aveva da dire.

Cosa significa “cura della pelle naturale”?

“Mentre il termine naturale può indicare qualcosa raccolto in natura, il suo uso in tutti i prodotti di bellezza, compresa la cura della pelle, in realtà non significa nulla perché non è regolamentato.”

Esiste una regolamentazione sui prodotti per la cura della pelle naturale?

“Non esiste un ente governativo negli Stati Uniti che regola i prodotti per la cura della pelle naturale, ma ci sono varie organizzazioni internazionali indipendenti che le aziende possono richiedere per verificare il loro livello di” naturale “. Prendi Ecocert nell'Unione Europea o la Soil Association nel Regno Unito per esempio. Il problema: concentrarsi su quanto sia naturale un prodotto non riesce a considerare la sicurezza di un prodotto. Se un siero per il viso è naturale al 95 percento, è fantastico, ma cosa c'è in quell'altro cinque percento? “

OK, quindi in che modo la cura della pelle naturale è diversa dalla cura della pelle pulita?

“Beh, anche questo è un po 'complicato. Allo stesso modo non esiste una regolamentazione per la cura della pelle naturale, né esiste una regolamentazione per la cura della pelle pulita. Generalmente, la cura della pelle pulita si riferisce a prodotti realizzati senza ingredienti potenzialmente dannosi, al contrario della cura della pelle naturale, che è fatta con un certo livello di ingredienti naturali. Perché questa distinzione è importante? Ci sono molti ingredienti naturali che sono pericolosi per la salute umana, come il talco, ad esempio, che possono contenere amianto. E ci sono molti ingredienti sintetici che sono perfettamente sicuri per l'uomo e l'ambiente, come l'acido ialuronico (sì, è tipicamente sintetico) “.

“Questa mancanza di regolamentazione è il motivo per cui noi di True Botanicals facciamo affidamento sulla certificazione di terze parti di un'organizzazione chiamata MADE SAFE. Il loro team di scienziati esamina le ultime ricerche ed esamina il profilo completo di sicurezza di un prodotto – ogni ingrediente e ogni ingrediente all'interno di quell'ingrediente – per assicurarsi che non costituisca una minaccia per la salute umana o ambientale. E considerano anche se un particolare ingrediente naturale sia una scelta veramente sostenibile. È il processo di certificazione più rigoroso e completo disponibile “.

Quindi è tutta la cura della pelle pulita naturale?

“C'è un sacco di crossover: ad esempio, diamo la priorità agli ingredienti naturali nelle nostre formule perché credo che, per la maggior parte delle cose, la risposta possa davvero essere trovata in natura. Ma in genere “clean skincare” mescola sintetici sicuri e naturali sicuri “.

Esiste una certa percentuale di ingredienti naturali che classifica un prodotto come “naturale”?

“No! In effetti, potresti ricoprire la parola naturale su tutta l'etichetta del tuo prodotto e il tuo elenco di ingredienti potrebbe essere pieno zeppo di soli prodotti petrolchimici. Ecco perché è così importante lavorare con un'organizzazione non profit di terze parti come MADE SAFE e concentrarsi sulla classificazione che alla fine ha un impatto sul benessere attuale e futuro delle persone, della fauna selvatica, del nostro suolo, dei nostri oceani e altro ancora. ”

OK, ricapitoliamo.

Il termine “naturale”, in relazione alla cura della pelle, non è regolamentato. Ciò significa che qualsiasi marchio può usare il termine sui propri prodotti indipendentemente dal fatto che siano realizzati con ingredienti naturali al 100% o naturali all'1%. È più utile guardare a marchi che hanno un livello di certificazione che fa il controllo per te (come fa True Botanicals). Uso personalmente questo metodo quando scelgo i miei prodotti per la cura della pelle. È fantastico se i prodotti sono naturali, ma non è tutto ciò che cerco.

Ora che la grinta grossa è fuori mano, è finalmente arrivato il momento di approfondire: i miei consigli. Poiché il mio compito è testare e controllare i prodotti di bellezza in base ai loro risultati, sono abbastanza esigente con la mia routine di cura della pelle. Uso solo i prodotti più naturali e puliti, perché è quello a cui tengo personalmente. Come ho detto, non sono un medico o un dermatologo, quindi posso solo consigliare prodotti che hanno funzionato per la mia pelle mista. Andiamo a questo.

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Come qualcuno che utilizzava quotidianamente lo scrub schiumogeno alla pompelmo rosa senza olio di Neutrogena senza olio, puoi immaginare la mia sorpresa quando ho scoperto che la mia zona a T oleosa naturalmente non beneficiava di prodotti senza olio (possono causare la pelle per compensare eccessivamente e produrre Di Più olio). Né le mie guance secche adoravano quelle microsfere di plastica che le spogliavano ulteriormente di oli naturali, due volte al giorno ogni giorno. Entra in questo purificante, leggermente granuloso e rivoluzionario. È fatto con oli naturali di chia e moringa per nutrire e idratare la pelle, oltre a quattro enzimi di frutta che conferiscono un po 'di consistenza grintosa, che aiutano a eliminare il trucco, lo sporco, lo sporco e persino le cellule morte della pelle nel modo più delicato possibile. Al mattino, mi sono bagnata la faccia con un po 'd'acqua prima di massaggiare due pompe di questo detergente dappertutto, sciacquandole e asciugandole. Non è necessaria una doppia pulizia per una pelle pulita e radiosa senza sostanze chimiche aggressive.

Compralo ($ 58)

Il prossimo è un nuovo prodotto di Isla, un marchio di bellezza che si concentra sulla trasparenza. Questa combinazione toner / essenza fa parte della sua linea di prodotti di base, che fornisce ingredienti naturali provenienti da tutto il mondo in base a dove sono più abbondanti. Questo particolare toner è realizzato con ingredienti naturali al 100% provenienti dall'Australia (come le vitamine A, C ed E più un complesso Wilberry ricco di antiossidanti), come chiaramente indicato sulla confezione. Come qualcuno che in precedenza utilizzava anche astringenti quotidianamente per eliminare le imperfezioni, sono rimasto sorpreso dalla delicatezza di questo toner e dall'estrema mancanza di bruciore. Aiuta a rimuovere eventuali oli in eccesso dal mio detergente e prepara anche la mia pelle ad assorbire meglio il resto dei miei prodotti per la cura della pelle.

Compralo ($ 70)

Goop ha standard elevati quando si tratta di bellezza non tossica, quindi non esito mai a comprare qualcosa sul suo sito, soprattutto quando si tratta della linea di prodotti del marchio. Questo nuovo siero ha un 20% di vitamina C estremamente potente per colpire l'iperpigmentazione e illuminare la pelle, con l'aggiunta di acido ialuronico per aggiungere idratazione. A differenza della maggior parte dei sieri di vitamina C, viene fornito con una polvere e un attivatore liquido, che si combinano appena prima dell'uso per garantire la potenza fino alla fine dell'uso. Adoro anche che la consistenza sia super liquida, quindi sprofonda e non ottengo alcuna appiccicosità che di solito deriva dai sieri a base di HA.

Compralo ($ 125)

L'idratante è il mio prodotto per la cura della pelle preferito, ma cerco sempre nuove formule. Ultimamente, sono stato ossessionato da questa crema da giorno idratante e riparatrice di Grown Alchemist per i suoi ingredienti naturali, profumo pulito e fresco e finitura opaca. Molti prodotti naturali in realtà non hanno un odore sorprendente, perché non c'è alcuna aggiunta di fragranza arbitraria, ma adoro il fatto che questo prodotto usi olii essenziali ed estratti vegetali per offrire un aroma edificante al mattino. Un'altra cosa da notare è il tubo di alluminio, che può essere completamente riciclato per ridurre gli sprechi.

Compralo ($ 49)

Come accennato, fortunatamente non ho mai lottato immensamente con l'acne, ma ciò non significa che non ho mai avuto imperfezioni: ne ho avute molte e continuo a prenderle nei miei 30 anni. Ecco perché adoro un olio per il viso chiarificante per il giorno che idrata la pelle e aiuta anche a schiarire i pori e respingere le eruzioni cutanee. Questo prodotto è amato da molti per i suoi ingredienti naturali come l'estratto di alghe e oli di canapa, zucca e semi d'uva. Nei giorni in cui ho bisogno di una crema idratante più leggera o mi sento un po 'congestionato, userò questo olio anziché della mia crema idratante.

Compralo ($ 110)

Tutta questa linea di bellezza è composta da estratti selvatici, antiossidanti e schiarenti di piante d'alta quota nel Wyoming, che le conferiscono una tonalità rosa chiaro naturale. Ha una consistenza più spessa rispetto alla maggior parte delle creme per gli occhi, che si sente super nutriente e idratante e leviga e rimpolpa la delicata pelle sotto gli occhi, riempiendo immediatamente linee e pieghe.

Compralo ($ 62)

Ultimo, ma certamente non meno importante, è la protezione solare. Preferisco l'SPF minerale alle formule chimiche per le sue naturali capacità di bloccare i raggi UV. La crema solare minerale (anche chiamata fisica) funziona come uno scudo, bloccando fisicamente il sole dal bruciore della pelle, mentre la protezione solare chimica assorbe la luce solare e la disperde. Questo prodotto è realizzato con zinco al 100%, ma non lascia la minima dominante bianca, grazie alla sua leggera tinta rosata. Lo uso al posto del trucco in estate nelle mie belle giornate di pelle e sotto il trucco tutto l'anno.

Compralo ($ 42)

Cosa posso dire, adoro questo detergente per olio. Come accennato, lo uso sulla pelle umida al mattino per creare più di una schiuma cremosa. Ma di notte, lo uso direttamente sulla pelle asciutta per rimuovere il trucco, quindi aggiungo acqua per sciacquarlo via.

Compralo ($ 58)

Un altro dei miei preferiti da Mara è l'Algae Retinol Face Oil. A differenza della maggior parte dei prodotti a base di retinolo, questo è sospeso in oli naturali (come la schiuma di prato e i semi di cannabis sativa), quindi non è così secco sulla mia pelle. Non ricevo alcuno di quel rossore rivelatore o peeling come ho visto con altri prodotti di retinolo, il che mi permette di usarlo quasi ogni singola notte senza irritazione. È difficile saltare un giorno in cui ho visto un incredibile aumento della luminosità e una riduzione delle linee sottili e delle imperfezioni dall'uso. Anche se è fatto con fonti naturali di retinolo (vitamina A), è ancora abbastanza potente, quindi suggerisco di iniziare da uno a due giorni alla settimana prima di salire.

Compralo ($ 120)

Oh, Weleda, quanto ti amo. Questo marchio svizzero esiste dal 1920 ed è da allora leader nella cura della pelle biologica e naturale. Questa crema per il viso super ricca è probabilmente il suo prodotto più popolare per la sua formula estremamente idratante che è così densa che sembra quasi colla. Non lasciarti spaventare, però: una volta che si riscalda sulla pelle, si scioglie e si trasforma in una finitura oleosa. Ingredienti come gli acidi grassi essenziali, la vitamina E, la pansé organica e l'estratto di fiori di calendula organici mi hanno persino aiutato a riparare la pelle dopo un incidente di esfoliazione. Quando ho visto quanto fosse curativa, ho iniziato ad aggiungerlo alla mia routine di cura della pelle notturna per aiutare con l'idratazione generale.

Compralo ($ 19)

Questo marchio australiano per la cura della pelle è uno dei miei go-to-go per prodotti veramente naturali. Sono stato un fan della sua crema per gli occhi per anni, grazie alla sua consistenza super spessa da una mescolanza di oli e burri che gli consente di affondare facilmente nella pelle delicata. Inoltre l'aggiunta di collagene a base vegetale aiuta a levigare le linee sottili e le zampe di gallina, due delle mie principali preoccupazioni in questi giorni.

Compralo ($ 38)

Last up è uno dei miei prodotti preferiti di tutti i tempi: Uma Oils Ultimate Brightening Face Oil. Mi è stato presentato questo marchio circa un anno fa e ho già esaminato tre bottiglie del materiale. Puzza sorprendente grazie al legno di sandalo e agli oli essenziali di rosa, che idratano in profondità anche la pelle per un bagliore illuminato dall'interno. Prima di premere quattro o cinque gocce sulla pelle, mi strofino i palmi delle mani e respiro il profumo per benefici aromaterapici. Poi lo accarezzo sulla pelle come l'ultimo passo della mia routine fino a quando non viene assorbito. Poiché l'olio è più denso dell'acqua, fungerà da barriera protettiva per sigillare tutta l'umidità e i nutrienti del resto della routine (se metti olio prima dell'idratante, le tue creme non saranno effettivamente in grado di penetrare nella pelle) . Posso davvero dire se non lo uso per un giorno o due: la mia pelle è più opaca, più secca e seriamente infelice.

$ 131 su Amazon

A volte ho bisogno di qualcosa di diverso dai miei prodotti di tutti i giorni. Ad esempio, quando la mia pelle si sente congestionata, applico questa maschera sorprendentemente idratante. A differenza della maggior parte delle formule di argilla, questa non succhia ogni grammo d'olio dalla mia pelle. Piuttosto, l'argilla glaciale ultra fine rimuove delicatamente lo sporco, le sostanze inquinanti e le impurità ripristinando l'umidità essenziale. Inoltre, adoro il suo profumo leggermente floreale e la consistenza leggera che lo rendono un sogno da applicare e sedersi per 20 minuti mentre si asciuga.

Compralo ($ 75)

Quando ho bisogno di prendere di mira e asciugare un digiuno, mi rivolgo alla lozione per imperfezioni di Indie Lee. Grazie a una miscela di argilla, acido salicilico e ossido di zinco, questa roba non si scherza e di solito succhia tutto il gunk durante la notte, aiutando a curare i brufoli alla velocità della luce. Hai solo bisogno di una piccola quantità, quindi scuoto la bottiglia, immergo un Q-tip all'interno e lo tampone sulle imperfezioni che hanno bisogno di più amore. Di mattina sono visibilmente più piccoli e meno arrabbiati, è piuttosto sorprendente.

Compralo ($ 26)

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PureWow può ricevere una parte delle vendite dai prodotti acquistati da questo articolo, creato indipendentemente dai dipartimenti editoriale e di vendita di PureWow.

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_________________________________________________________________________________________________________

SICUREZZA DEGLI STATI UNITI E COMMISSIONE DI SCAMBIO

WASHINGTON, DC 20549

Modulo 10-K

RELAZIONE ANNUALE AI SENSI DELLA SEZIONE 13 O 15 (d) DEL

ATTO DI SCAMBIO DI TITOLI DEL 1934

Per l'esercizio finanziario chiuso al 31 dicembre 2019

di

CUMBERLAND PHARMACEUTICALS INC.

Una società del Tennessee

Identificazione del datore di lavoro IRS n. 62-1765329

Numero di fascicolo della Commissione 001-33637

2525 West End Avenue, Suite 950

Nashville, Tennessee37203

(615) 255-0068

Titoli registrati ai sensi della Sezione 12 (b) della Legge:

Titolo di ogni classe

Simbolo / i di trading

Nome di ogni scambio su cui registrato

Azioni ordinarie, valore nominale di $ 0,00 per azione

CPIX

Nasdaq Global Select Market

Titoli registrati ai sensi della Sezione 12 (g) della Legge: Nessuna

Cumberland Pharmaceuticals Inc. non è un emittente stagionato noto, come definito nella Regola 405 del Securities Act.

Cumberland Pharmaceuticals Inc. è tenuta a presentare relazioni ai sensi della Sezione 13 o della Sezione 15 (d) della Legge. Cumberland Pharmaceuticals Inc. (1) ha archiviato tutte le segnalazioni che devono essere archiviate dalla Sezione 13 o 15 (d) del Securities Exchange Act del 1934 nei 12 mesi precedenti e (2) è stata soggetta a tali requisiti di archiviazione in passato 90 giorni.

Cumberland Pharmaceuticals Inc. ha inviato elettronicamente e pubblicato sul proprio sito Web aziendale tutti i file di dati interattivi che devono essere inviati e pubblicati ai sensi della regola 405 del regolamento S-T (§232.405 del presente capitolo) nei 12 mesi precedenti.

Cumberland Pharmaceuticals Inc. è un filer non accelerato come definito nella Regola 12b-2 dello Exchange Act e non è una società di comodo.

Il valore di mercato aggregato delle azioni ordinarie detenute da non affiliate al 28 giugno 2019 era di $ 57.172.655. Il numero di azioni ordinarie del dichiarante, nessun valore nominale, in circolazione al 16 marzo 2020 era di 15.181.442.

DOCUMENTI INCORPORATI PER RIFERIMENTO

Alcune informazioni richieste nella Parte III del Modulo 10-K sono incorporate come riferimento dalla Dichiarazione Proxy del dichiarante per l'assemblea annuale degli azionisti del 2020.

_________________________________________________________________________________________________________

CUMBERLAND PHARMACEUTICALS INC. E SUSSIDIARI

Indice

PARTE I

Articolo 1. Affari.

L'AZIENDA

Cumberland Pharmaceuticals Inc. (“Cumberland”, la “Società” o come utilizzato nel contesto di “noi”, “noi” o “nostro”), è una società farmaceutica specializzata focalizzata sull'acquisizione, lo sviluppo e la commercializzazione di marchi prodotti da prescrizione. I nostri mercati target principali sono le cure acute ospedaliere e la gastroenterologia. Queste specialità mediche sono caratterizzate da basi di prescrizione relativamente concentrate che riteniamo possano essere penetrate efficacemente da piccole forze di vendita mirate. Cumberland è impegnata a fornire prodotti innovativi che migliorano la qualità delle cure per i pazienti e rispondono a esigenze mediche insoddisfatte o scarsamente soddisfatte. Promuoviamo i nostri prodotti approvati attraverso le nostre forze di vendita ospedaliere e sul campo negli Stati Uniti e stiamo creando una rete di partner internazionali per portare le nostre medicine ai pazienti nei loro paesi.

Il nostro portafoglio di marchi approvati dalla FDA comprende:

Acetadote®(acetilcisteina) Iniezione, per il trattamento dell'avvelenamento da paracetamolo;

Caldolor®(ibuprofene) Iniezione, per il trattamento del dolore e della febbre;

Kristalose®(lattulosio) per Oral Solution, un lassativo di prescrizione, per il trattamento della costipazione cronica e acuta;

Omeclamox®-Pak, (omeprazolo, claritromicina, amoxicillina) per il trattamento di Helicobacter pylori (H. pylori) infezione e ulcera duodenale correlata;

Vaprisol®(conivaptan) Iniezione, per aumentare i livelli sierici di sodio in pazienti ospedalizzati con iponatriemia euvolemica e ipervolemica;

Vibativ®(telavancina) Iniezione, per il trattamento di alcune gravi infezioni batteriche, inclusa la polmonite batterica acquisita in ospedale e associata al ventilatore, nonché infezioni complicate della pelle e della struttura cutanea; e

RediTrex(metotressato) Iniezione, per il trattamento dell'artrite psoriasica reumatoide, idiopatica giovanile e grave attiva, nonché della psoriasi invalidante.

Inoltre, abbiamo in corso programmi clinici di Fase II per valutare i nostri candidati al prodotto ifetroban in pazienti con cardiomiopatia associata a distrofia muscolare di Duchenne (“DMD”), sclerosi sistemica (“SSc”) e malattia respiratoria esacerbata dall'aspirina (“AERD”). Abbiamo anche completato i programmi clinici di fase II con ifetroban in pazienti con sindrome epatorenale (“HRS”) e pazienti con ipertensione portale (“PH”).

La Società dispone sia di sviluppo del prodotto che di capacità commerciali e riteniamo di poter sfruttare la nostra infrastruttura esistente per supportare la crescita prevista. Il nostro team di gestione è composto da veterani dell'industria farmaceutica con esperienza in sviluppo commerciale, sviluppo di prodotti, regolamentazione, produzione, vendite, marketing e finanza. Il nostro team di sviluppo aziendale identifica, valuta e negozia accordi di acquisizione, licenza e co-promozione del prodotto. Il nostro team di sviluppo prodotto crea formulazioni di prodotti proprietari, gestisce i nostri studi clinici, prepara tutte le comunicazioni normative e il personale del nostro call center medico. I nostri professionisti della qualità e della produzione supervisionano la produzione, il rilascio e la spedizione dei nostri prodotti. Il nostro team di marketing e vendite è responsabile delle nostre attività commerciali e lavoriamo a stretto contatto con i nostri partner di distribuzione per garantire la disponibilità e la consegna dei nostri prodotti.

La strategia di crescita di Cumberland prevede l'ottimizzazione del potenziale dei nostri marchi esistenti, continuando nel contempo a costruire un portafoglio di prodotti differenziati. Al momento disponiamo di sette prodotti approvati dalla FDA in vendita negli Stati Uniti. Attraverso i nostri partner internazionali, stiamo lavorando per portare le nostre medicine ai pazienti nei loro paesi. Cerchiamo anche opportunità per espandere i nostri prodotti in ulteriori popolazioni di pazienti attraverso studi clinici, nuove presentazioni e il nostro supporto per studi selezionati avviati dallo sperimentatore. Perseguiamo inoltre attivamente opportunità di acquisire ulteriori prodotti commercializzati, nonché candidati ai prodotti di sviluppo in fase avanzata nelle nostre specialità mediche target. Il nostro team clinico sta sviluppando una pipeline di candidati per nuovi prodotti in gran parte per soddisfare esigenze mediche insoddisfatte.

Inoltre, stiamo completando queste attività con lo sviluppo di farmaci nella fase precedente della Cumberland Emerging Technologies (“CET”), la nostra filiale di proprietà della maggioranza. CET collabora con istituti di ricerca accademici per identificare e far progredire candidati promettenti per nuovi prodotti, che Cumberland ha l'opportunità di sviluppare e commercializzare ulteriormente.

Siamo stati costituiti nel 1999 e sin dall'inizio abbiamo avuto sede a Nashville, nel Tennessee. Nel corso del 2009 abbiamo completato un'offerta pubblica iniziale delle nostre azioni ordinarie e quotazione alla borsa di Nasdaq. Il nostro indirizzo del sito Web è www.cumberlandpharma.com. Mettiamo a disposizione attraverso il nostro sito Web i nostri rapporti annuali sul modulo 10-K, i rapporti trimestrali sul modulo 10-Q, i rapporti attuali sul modulo 8-K e tutti i comunicati stampa rilevanti, altri documenti e modifiche a tali rapporti non appena ragionevolmente possibile dopo la loro deposito presso la Securities and Exchange Commission degli Stati Uniti, (“SEC”). Questi documenti sono anche disponibili al pubblico all'indirizzo www.sec.gov.

PRODOTTI

I nostri prodotti chiave includono:

Prodotti Indicazione Stato

Acetadote®

Avvelenamento da paracetamolo commercializzato

Caldolor®

Pain and Fever commercializzato

Kristalose®

Costipazione cronica e acuta commercializzato

Omeclamox®-Pak

Infezione da H. pylori e correlata ulcera duodenale commercializzato

Vaprisol®

Iponatriemia euvolemica e ipervolemica commercializzato

Vibativ®

Infezioni batteriche gravi commercializzato
RediTrex ™ Artrite e psoriasi Approvato

Acetadote®

Acetadote è una formulazione endovenosa di N-acetilcisteina, indicata per il trattamento della tossicità epatica associata all'avvelenamento da paracetamolo. Acetadote, è stato disponibile negli Stati Uniti dall'introduzione del prodotto da parte di Cumberland nel 2004 attraverso la nostra forza vendita ospedaliera. L'acetadote è in genere utilizzato nei reparti di emergenza dell'ospedale per prevenire o ridurre i potenziali danni al fegato derivanti da un sovradosaggio di paracetamolo, un ingrediente comune in molti prodotti da banco e antidolorifici e antidolorifici. Il sovradosaggio di paracetamolo continua a essere una delle principali cause di avvelenamenti segnalati dai dipartimenti di emergenza ospedaliera negli Stati Uniti e Acetadote è diventato uno standard di cura per il trattamento di questa condizione potenzialmente pericolosa per la vita.

Acetadote ha ricevuto l'approvazione della Food and Drug Administration ('FDA') degli Stati Uniti come farmaco orfano, che ha fornito sette anni di esclusività di marketing dalla data di approvazione. In relazione all'approvazione della FDA di Acetadote, ci siamo impegnati in alcune attività post-marketing per il prodotto. Il completamento del nostro primo impegno di Fase IV ha comportato l'approvazione da parte della FDA del 2006 di un'etichettatura estesa per il prodotto per l'uso in pazienti pediatrici. Il completamento del nostro secondo impegno di Fase IV ha comportato un'ulteriore revisione dell'etichettatura del prodotto con l'approvazione della FDA di

ulteriori dati sulla sicurezza nel 2008. Il completamento del nostro terzo e ultimo impegno di Fase IV nel 2010 è culminato con l'approvazione della FDA di una nuova formulazione per il prodotto. La formulazione di prossima generazione, non contiene acido tetracetico etilendiamminico (“EDTA”) o altri agenti stabilizzanti, agenti chelanti o conservanti. All'inizio del 2011, Cumberland ha introdotto questa nuova formulazione Acetadote in sostituzione della forma originale del prodotto che non produciamo più.

Nel giugno 2013, la FDA ha approvato l'etichettatura aggiornata per Acetadote, rivedendo l'indicazione del prodotto e fornendo nuove linee guida di dosaggio per specifiche popolazioni di pazienti. Di conseguenza, ora è inclusa una guida per il dosaggio per i pazienti di peso superiore a 100 kg e una nuova lingua è stata aggiunta per avvisare i fornitori di assistenza sanitaria che, in determinate situazioni cliniche, la terapia dovrebbe essere estesa per alcuni pazienti.

A partire dal 2012, l'Ufficio brevetti e marchi degli Stati Uniti (“USPTO”) ci ha rilasciato una serie di brevetti associati al nostro prodotto Acetadote. Questi brevetti sono discussi nella parte I, punto I, “Affari – Marchi e brevetti“di questo modulo 10-K. L'8 novembre 2012, abbiamo appreso che la FDA ha approvato una nuova domanda abbreviata di droga (ANDA) presentata da InnoPharma, Inc. e riferita ad Acetadote. Tale prodotto, con la vecchia formulazione contenente EDTA, è stato successivamente introdotto da APP, una divisione di Fresenius Kabi USA, alla fine del 2012. All'inizio del 2013, abbiamo stipulato un accordo con Perrigo Company con conseguente distribuzione della nostra acetilcisteina generica autorizzata iniezione (il nostro “generico autorizzato”). Sia Acetadote che il nostro generico autorizzato utilizzano la nuova formulazione priva di EDTA, che ha rappresentato una quota di mercato significativa nel corso del 2019.

Nel novembre 2015, un giudice dell'Illinois ha emesso una sentenza definitiva a favore di Cumberland Pharmaceuticals Inc. in un caso di brevetto associato ad Acetadote. Decidendo a favore di Cumberland, il tribunale ha confermato la validità del brevetto che comprende la nostra formulazione senza EDTA e ha una durata fino all'agosto 2025. Il tribunale ha anche concesso un'ingiunzione permanente che impedisce agli sfidanti di commercializzare una versione generica della nostra formulazione di prodotto Acetadote proprietaria prima la scadenza del brevetto di Cumberland nell'agosto 2025.

Il 26 gennaio 2017, una corte d'appello ha affermato la sentenza del tribunale distrettuale a favore della società sostenendo il brevetto Acetadote di Cumberland e respinto espressamente la richiesta di validità.

Caldolor®

Caldolor, la nostra formulazione endovenosa di ibuprofene, è stato il primo prodotto iniettabile approvato negli Stati Uniti per il trattamento sia del dolore che della febbre. Abbiamo condotto una serie di studi clinici su oltre novecento pazienti adulti per sviluppare i dati a supporto della nostra presentazione FDA per la registrazione del prodotto. La FDA ha approvato Caldolor per la commercializzazione negli Stati Uniti nel 2009 a seguito di una revisione prioritaria. Il prodotto è stato indicato per l'uso negli adulti come unico trattamento per la gestione del dolore da lieve a moderato e per la gestione del dolore da moderato a grave in aggiunta agli analgesici oppioidi. È stata anche la prima terapia endovenosa approvata dalla FDA per il trattamento della febbre.

Alla fine del 2009, abbiamo lanciato Caldolor e stoccato il prodotto presso i principali grossisti che servono ospedali in tutta la nazione. Inizialmente abbiamo lavorato per stabilire un gruppo centrale di strutture mediche che approvassero e acquistassero il prodotto e quindi ci siamo concentrati sulla costruzione di un volume maggiore di vendite e sul trattamento di una gamma più ampia di pazienti all'interno di tali strutture fornite. Promuoviamo Caldolor negli Stati Uniti attraverso la nostra forza vendita ospedaliera dedicata.

Abbiamo completato una serie di studi di Fase IV per raccogliere ulteriori dati a supporto del nostro prodotto Caldolor. Tali studi clinici hanno coinvolto altri 1.000 pazienti, pazienti adulti e pediatrici. Questi studi includevano dati su un tempo di infusione ridotto e la somministrazione pre-chirurgica del prodotto. Per affrontare il nostro impegno di Fase IV nei confronti della FDA, questi studi includevano anche la valutazione del prodotto per la riduzione della febbre nei bambini ospedalizzati e il trattamento del dolore nei bambini sottoposti a interventi chirurgici di tonsillectomia.

Nel 2015 abbiamo ricevuto l'approvazione della FDA per l'uso di Caldolor in pazienti pediatrici di età pari o superiore a sei mesi. Caldolor è il primo e unico farmaco antinfiammatorio non steroideo iniettabile (FANS) approvato per l'uso nei bambini. Abbiamo quindi avviato uno studio per raccogliere dati sull'uso di Caldolor nei bambini di età compresa tra la nascita e i sei mesi. Le iscrizioni a quello studio sono state completate nel 2019.

All'inizio del 2018, abbiamo completato e presentato la domanda di approvazione FDA per un prodotto Caldolor di nuova generazione con una presentazione e una formulazione migliorate. Nell'aprile 2018, la FDA ha stabilito che la domanda era completa e ci ha comunicato l'accettazione della richiesta di revisione. Vi sono state poi diverse comunicazioni con domande poste attraverso molteplici emendamenti che sono stati sottoposti alla domanda.

Nel gennaio 2019, la FDA ha approvato la domanda per il nostro prodotto Caldolor di prossima generazione. Ad aprile 2019, abbiamo iniziato le spedizioni iniziali del prodotto per selezionare i clienti. Durante il terzo e il quarto trimestre del 2019, c'era una domanda crescente per il nuovo prodotto da questi account selezionati e abbiamo iniziato a pianificare un lancio su vasta scala nel 2020.

Kristalose®

Kristalose è un lassativo da prescrizione somministrato per via orale per il trattamento della costipazione acuta e cronica. Una formulazione cristallina innovativa di polvere secca di lattulosio, Kristalose è progettata per migliorare l'accettazione e la conformità dei pazienti. Kristalose è l'unico lassativo da prescrizione disponibile in pacchetti di polvere pre-misurati.

La Kristalose si dissolve facilmente in quattro once di acqua, offrendo ai pazienti un'alternativa praticamente priva di gusto, senza grana ed essenzialmente priva di calorie agli sciroppi di lattulosio. Abbiamo condotto uno studio di preferenza che indicava che il settantasette per cento dei pazienti intervistati preferisce il gusto, la consistenza e la portabilità di Kristalose rispetto a prodotti simili in forma di sciroppo.

Abbiamo acquisito i diritti esclusivi di commercializzazione negli Stati Uniti a Kristalose nel 2006, riunito una forza vendita sul campo dedicata e rilanciata nel settembre 2006 come marchio Cumberland. Abbiamo indirizzato i nostri sforzi di vendita ai medici che sono i più prolifici scrittori di lassativi da prescrizione, compresi gastroenterologi e internisti. Abbiamo integrato questa promozione personale con campagne di telemarketing per ampliare la nostra portata e il supporto del prodotto.

Alla fine del 2011, attraverso una serie di transazioni, abbiamo stipulato un accordo per l'acquisizione di attività associate al marchio Kristalose tra cui il marchio Kristalose e la registrazione FDA.

Usando i dati sulle preferenze come pietra angolare dei nostri sforzi di marketing, abbiamo riposizionato il marchio all'inizio del 2014. La strategia di marketing che è proseguita nel 2019 includeva un programma di coupon per pazienti migliorato e una copertura di assistenza gestita estesa per il prodotto.

Abbiamo aggiunto un partner di co-promozione per fornire supporto al marchio nel 2017. Poly Pharmaceuticals sta promuovendo Kristalose a obiettivi medici non coperti dalle nostre forze di vendita sul campo. Nel 2018 abbiamo aggiunto un altro partner di co-promozione, 2R Pharmaceuticals che sta riconfezionando Kristalose e presentandolo con nuovi obiettivi medici aggiuntivi.

Omeclamox®-Pak

Molte ulcere del tratto gastrointestinale sono causate da un'infezione del batterio Helicobacter pylori (“H. pylori”). Omeclamox-Pak è un prodotto di prescrizione di marca utilizzato per il trattamento di queste infezioni e della relativa ulcera duodenale. Questo prodotto innovativo combina tre farmaci ben noti e ampiamente prescritti: omeprazolo, claritromicina e amoxicillina. Omeclamox-Pak è stato il primo farmaco combinato a tripla terapia approvato dalla FDA a contenere l'omeprazolo come inibitore della pompa protonica, che agisce per ridurre la quantità di acido prodotta dallo stomaco. La claritromicina e l'amoxicillina sono entrambi agenti antibiotici che ostacolano la crescita dei batteri H. pylori. L'interazione di questi agenti consente al rivestimento dello stomaco di guarire efficacemente. I farmaci sono confezionati insieme su comode schede di dosaggio giornaliere, rendendo semplice seguire la dose due volte al giorno prima dei pasti.

Mentre ci sono prodotti combinati concorrenti, Omeclamox-Pak è uno dei pochi marchi commercializzati attivamente per questa condizione. Inoltre, rispetto ai concorrenti, Omeclamox-Pak comporta l'onere della pillola più basso e il minor numero di giorni di terapia. Il nostro coinvolgimento con Omeclamox-Pak è iniziato nell'ottobre 2013, attraverso un accordo di co-promozione con Pernix Therapeutics (“Pernix”). Nel novembre 2015, Cumberland ha stipulato un accordo di licenza e fornitura esclusiva con Gastro-Entero Logic, LLC (“GEL”), ha assunto la piena responsabilità commerciale di Omeclamox-Pak negli Stati Uniti e ha concluso i nostri accordi con Pernix. Cumberland divenne responsabile della distribuzione, dei conti nazionali e di tutta la promozione delle vendite di Omeclamox-Pak ai sensi dell'accordo GEL.

Nel dicembre 2018, abbiamo concluso un accordo con GEL per l'acquisizione di tutte le rimanenti attività associate a Omeclamox-Pak, compresa l'approvazione FDA del prodotto, nonché i marchi nazionali e internazionali. La chiusura di questa transazione ha posto fine ai pagamenti di Cumberland di royalties e commissioni di produzione a GEL e ci siamo assunti la responsabilità del mantenimento dell'approvazione FDA del Prodotto e della supervisione della produzione e dell'imballaggio del Prodotto.

La nostra forza vendita sul campo promuove Omeclamox-Pak nel segmento di mercato della gastroenterologia, che rappresenta il componente più importante della base di prescrizione per questo prodotto. Integriamo questa promozione personale attraverso campagne di telemarketing per espandere il supporto e l'uso del prodotto. Abbiamo anche stabilito una serie di contratti per fornire una copertura di assistenza gestita per Omeclamox-Pak.

Vaprisol®

All'inizio del 2014, abbiamo stipulato un accordo con Astellas Pharma US, Inc. (“Astellas”) per acquisire Vaprisol, inclusi alcuni diritti sui prodotti, proprietà intellettuale e beni correlati. Vaprisol è un marchio di prescrizione indicato per aumentare i livelli sierici di sodio in pazienti ospedalizzati con iponatriemia euvolemica e ipervolemica. Il prodotto è stato sviluppato e registrato da Astellas. È uno dei due prodotti di prescrizione di marca indicati per il trattamento dell'iponatriemia e l'unico trattamento di marca somministrato per via endovenosa. Nel corso del 2019 è stata ripresa la normale fornitura del prodotto e lo abbiamo supportato attraverso la nostra divisione vendite ospedaliera.

L'iponatriemia, uno squilibrio del sodio sierico nell'acqua corporea, è il disturbo elettrolitico più comune tra i pazienti ospedalizzati. Questi disturbi elettrolitici si verificano quando la concentrazione di ioni di sodio nel plasma è inferiore al normale e sono spesso associati a una varietà di condizioni di terapia intensiva tra cui insufficienza cardiaca congestizia, insufficienza epatica, insufficienza renale e polmonite. Vaprisol aumenta il siero di sodio a livelli adeguati e favorisce la secrezione di acqua libera.

Abbiamo rilanciato la promozione attiva del marchio durante la metà del 2014 utilizzando la nostra forza vendita ospedaliera supportata da una serie di iniziative di marketing. Alla fine del 2017, abbiamo riscontrato ritardi nella produzione e nella fornitura del prodotto che hanno influito sulle sue vendite fino al secondo trimestre del 2018, quando è arrivato il nuovo inventario. Abbiamo quindi rifornito i canali di distribuzione di Vaprisol e aumentato il livello di inventario del marchio.

Vibativ®

Nel novembre 2018, la Società ha annunciato un accordo con Theravance Biopharma (“Theravance”) per acquisire le attività di Vibativ da Theravance e assumersi la responsabilità globale di Vibativ, comprese le attività di marketing, distribuzione, produzione e regolamentazione associate al marchio. Vibativ è un antinfettivo iniettabile brevettato e approvato dalla FDA per il trattamento di alcune gravi infezioni batteriche tra cui polmonite batterica acquisita in ospedale e associata al ventilatore e complicate infezioni della pelle e della struttura cutanea. Si rivolge a una gamma di agenti patogeni batterici Gram-positivi, compresi quelli che sono considerati difficili da trattare e resistenti a più farmaci.

Immediatamente dopo la chiusura, abbiamo avviato le spedizioni di Vibativ e ci siamo assunti la responsabilità della catena di approvvigionamento e della distribuzione del prodotto negli Stati Uniti. Vibativ è supportato dalla nostra divisione di vendita ospedaliera. Nel corso del 2019 abbiamo trasferito le responsabilità del marchio da Theravance a Cumberland.

Alla fine del 2019, abbiamo annunciato una pubblicazione in Malattie infettive e terapia, con risultati dello studio che mostrano tassi di guarigione numericamente superiori della telavancina rispetto alla vancomicina in un sottogruppo di pazienti che sono stati arruolati negli studi di fase 3 ATTAIN e avevano polmonite acquisita in ospedale causata da batteri con bassa suscettibilità alla vancomicina. Inoltre, una pubblicazione online in Droghe – Risultati del mondo reale, ha illustrato in dettaglio i risultati clinici positivi risultanti dal trattamento di più tipi di infezione con Vibativ, tra cui infezioni cutanee complicate, infezioni ossee e articolari, batteriemia ed endocardite e infezioni del tratto respiratorio inferiore.

RediTrex

Nel novembre 2016, abbiamo annunciato un accordo con Nordic Group B.V. per commercializzare la loro linea di prodotti in metotrexato negli Stati Uniti. Questa nuova linea di prodotti iniettabili è progettata per il trattamento di pazienti con artrite e psoriasi. Cumberland è responsabile della registrazione e della commercializzazione di questi prodotti, mentre Nordic gestirà la fornitura del prodotto. Nordic ha registrato e vende i propri prodotti a base di metotrexato in diversi paesi europei.

Alla fine del 2018, abbiamo completato l'invio e presentato alla FDA una nuova domanda di droga per i nostri prodotti metotrexato. A dicembre 2019, abbiamo ricevuto l'approvazione della FDA per RediTrex e abbiamo iniziato a pianificare il lancio nel 2020 di questa linea di prodotti.

Ethyol®

Nel maggio 2016, la Società ha annunciato un accordo con Clinigen Group Plc (“Clinigen”) in base al quale Cumberland ha acquisito i diritti esclusivi per la commercializzazione e la reintroduzione di Ethyol negli Stati Uniti. L'etolo è un farmaco citoprotettivo approvato dalla FDA contenente amifostina per iniezione. È indicato come terapia adiuvante per ridurre l'incidenza della xerostomia (secchezza delle fauci) come effetto collaterale nei pazienti sottoposti a radioterapia post-operatoria per carcinoma della testa e del collo. Riduce anche la tossicità renale cumulativa associata alla somministrazione ripetuta di cisplatino in pazienti con carcinoma ovarico avanzato. Secondo i termini dell'accordo, Cumberland è responsabile di tutte le attività di marketing, promozione e distribuzione del prodotto negli Stati Uniti.

Alla fine del 2016, abbiamo iniziato la distribuzione di Ethyol per iniezione ai grossisti negli Stati Uniti e abbiamo lanciato il supporto promozionale nazionale per il marchio da parte della nostra divisione vendite ospedaliere.

All'inizio del 2019 abbiamo avviato una revisione strategica dei nostri prodotti, partner e organizzazione. Di conseguenza, abbiamo concluso la nostra distribuzione e il supporto per Ethyol e trasferito le responsabilità del prodotto su Clinigen. Di conseguenza,Cumberland non sarà più coinvolto nella distribuzione, commercializzazione e promozione di Ethyol o di altri prodotti concorrenti dopo il 2019.

Totect®

Nel gennaio 2017, abbiamo annunciato un accordo esclusivo con Clinigen per la distribuzione del farmaco di supporto oncologico, Totect negli Stati Uniti. Si tratta di un farmaco di intervento oncologico di emergenza in ospedale approvato dalla FDA, indicato per il trattamento degli effetti tossici della chemioterapia con antraciclina. Tratta lo stravaso di antraciclina che si verifica quando il farmaco iniettato fuoriesce dai vasi sanguigni e circola nei tessuti circostanti nel corpo, causando gravi danni e gravi complicazioni. Totect può limitare tali danni senza la necessità di ulteriori interventi chirurgici o procedure e consente ai pazienti di continuare il loro trattamento anticancro essenziale.

Alla fine di luglio 2017, abbiamo avviato la distribuzione e la vendita di Totect (dexrazoxane hydrochloride) negli Stati Uniti. Ciò ha fatto seguito all'approvazione della FDA dell'etichettatura e del produttore del prodotto aggiornati per il prodotto. Alla fine di settembre 2017, abbiamo annunciato il rilancio di Totect negli Stati Uniti e abbiamo lanciato Totect durante una carenza nazionale di dexrazoxano alla fine del 2017, determinando una forte domanda iniziale per il prodotto. Nel corso del 2018 sono tornati numerosi prodotti competitivi, riducendo la quota di mercato di Totect.

A seguito della nostra revisione strategica, abbiamo concluso la distribuzione di Totect e trasferito i diritti e le responsabilità del marchio su Clinigen.

TUBATURA

La nostra pipeline di sviluppo include una serie di candidati al prodotto nello sviluppo di Fase II. Le nostre aree di interesse includono:

Sindrome epatorenale (“HRS”)

Nel 2011, abbiamo stipulato un accordo per acquisire i diritti di ifetroban, un nuovo prodotto candidato di Fase II. La nostra acquisizione dei diritti sul programma ifetroban comprende un ampio database clinico e un pacchetto di dati non clinici, nonché processi di produzione, know-how e proprietà intellettuale. Ifetroban è stato inizialmente sviluppato da una grande azienda farmaceutica per importanti indicazioni cardiovascolari. Quell'azienda condusse studi approfonditi per le loro indicazioni target e alla fine donò l'intero programma alla Vanderbilt University. I ricercatori di Vanderbilt hanno identificato ifetroban come un composto potenzialmente prezioso nel trattamento dei pazienti per diverse indicazioni di nicchia. Cumberland ha acquisito i diritti sul programma ifetroban da Vanderbilt a CET con l'intenzione di sviluppare il prodotto per diverse potenziali nuove indicazioni.

Abbiamo iniziato la produzione di una formulazione endovenosa di ifetroban e la FDA ha autorizzato la nostra nuova domanda sperimentale di nuovi farmaci (“IND”) per questo prodotto candidato. Abbiamo avviato lo sviluppo clinico con il marchio Hepatoren e stiamo valutando questo candidato per il trattamento di pazienti ospedalizzati in condizioni critiche che soffrono di sindrome epatorenale (“HRS”). L'HRS è una condizione pericolosa per la vita che coinvolge fegato e insufficienza renale, con un alto tasso di mortalità e nessuna terapia farmaceutica approvata negli Stati Uniti. Abbiamo completato uno studio di Fase II su sessantaquattro pazienti per valutare la sicurezza, l'efficacia e la farmacocinetica delle dosi crescenti di Hepatoren in HRS pazienti.

La progressione verso livelli di dose più elevati è stata rivista e approvata da un comitato di sicurezza indipendente. Lo studio è stato stratificato in pazienti di tipo I o di tipo II con HRS in base alla progressione della loro malattia.

I risultati migliori di questo studio hanno indicato che Hepatoren è stato complessivamente ben tollerato nei pazienti con HRS senza che siano stati rilevati problemi di sicurezza. Abbiamo archiviato i risultati di questo studio con la FDA e abbiamo iniziato a valutare il progetto per uno studio di efficacia di fase II di follow-on.

Malattia respiratoria esacerbata dall'aspirina (“AERD”)

Abbiamo completato la produzione e avviato lo sviluppo clinico di una formulazione orale di ifetroban con il marchio Boxaban. Stiamo valutando questo candidato per i pazienti che soffrono di malattia respiratoria esacerbata ('AERD'), noto anche come Triade di Samter, una condizione medica cronica che consiste di tre caratteristiche cliniche: asma, sinusite con poliposi nasale e sensibilità all'aspirina. L'AERD è caratterizzato da forti aumenti dei mediatori infiammatori e dell'attività piastrinica all'interno del sistema respiratorio. Circa un adulto asmatico su venti negli Stati Uniti soffre di AERD e la consapevolezza della malattia sta crescendo all'interno della comunità medica. Non esiste un trattamento farmaceutico approvato dagli Stati Uniti per l'AERD.

Abbiamo completato uno studio clinico iniziale di Fase II per valutare la sicurezza e la tollerabilità di Boxaban nei pazienti con AERD. Lo studio multicentrico ha coinvolto sedici pazienti in diversi centri medici statunitensi guidati dallo Scripps Research Institute. I risultati hanno indicato che Boxaban è stato ben tollerato senza problemi di sicurezza rilevati in pazienti con una storia di AERD.

All'inizio del 2017, la FDA ha autorizzato l'applicazione IND di Cumberland per il programma clinico AERD della Società. A seguito di questa autorizzazione, abbiamo avviato uno studio di efficacia di fase II multicentrico di follow-up per valutare l'efficacia di Boxaban in settantasei pazienti con AERD sintomatico. Le iscrizioni a questo studio multicentrico, controllato con placebo, sono proseguite nel 2019 in un numero crescente di centri per allergie e asma negli Stati Uniti.

Sclerosi sistemica (“SSc”)

Nell'aprile 2016 abbiamo annunciato l'aggiunta di Vasculan alla nostra pipeline. Attraverso il programma ifetroban di Cumberland, Cumberland ha avviato lo sviluppo clinico di capsule orali di ifetroban per il trattamento della sclerosi sistemica.

La sclerosi sistemica (“SSc”), chiamata anche sclerodermia, è una malattia autoimmune debilitante caratterizzata da fibrosi diffusa della pelle e degli organi interni, nonché disfunzione vascolare. Studi preclinici hanno dimostrato che ifetroban previene e può ripristinare la funzione cardiaca in un modello preclinico di ipertensione arteriosa polmonare. Questa malattia ha un'alta morbilità e la più alta mortalità specifica per caso di qualsiasi disturbo reumatico con il 50% dei pazienti che muoiono o sviluppano gravi complicanze interne agli organi entro 3 anni dalla diagnosi. Sebbene vengano utilizzati diversi farmaci per trattare la malattia della pelle associata alla SSc, non esiste un trattamento universalmente efficace per migliorare la funzione degli organi interni colpiti come polmoni, cuore e tratto gastrointestinale.

La FDA ha autorizzato la nostra applicazione IND per valutare la sicurezza e l'efficacia di Vasculan nei pazienti con SSc. Di conseguenza, abbiamo avviato uno studio multicentrico di fase II su trentaquattro pazienti con SSc. Le iscrizioni a questo studio randomizzato, controllato con placebo, sono proseguite in diversi centri di eccellenza della sclerodermia negli Stati Uniti nel 2019.

Portal Hypertinsion (“PH”)

Nel settembre 2016, abbiamo annunciato l'aggiunta di Portaban alla nostra pipeline. Cumberland ha avviato lo sviluppo clinico di Portaban per il trattamento dell'ipertensione portale (“PH”) associata a malattia epatica cronica. Studi preclinici hanno dimostrato che ifetroban può ridurre la pressione portale, l'infiammazione e la fibrosi in più modelli di danno epatico.

The FDA cleared our IND application for a clinical development program evaluating Portaban in thirty patients with PH. Following that clearance, a multicenter Phase II study was initiated. During 2018 enrollment in this randomized, placebo controlled study was completed.

This study was primarily designed to evaluate the safety of ifetroban treatment in this population and was not powered for any efficacy measurement. An initial review of the data from the study shows ifetroban was safe and well tolerated with no unexpected safety findings.

We also measured hepatic venous pressure. Patients enrolled had a greater degree of variability than expected in their hepatic venous pressure gradient, therefore no definitive conclusions could be made on the impact of ifetroban on modulating that gradient. A full analysis of the data to include biomarkers and exploratory endpoints is ongoing.

Duchenne Muscular Dystrophy ('DMD')

On September 24, 2019, Cumberland announced U.S. Food and Drug Administration ('FDA') Orphan Drug Grant funding for a new Phase II clinical program. The Company has initiated the clinical development of ifetroban for the treatment of cardiomyopathy associated with Duchenne Muscular Dystrophy ('DMD'). Based on preclinical findings, the FDA has cleared Cumberland's application to study ifetroban in DMD patients, 7 years of age and older. In addition, Cumberland has been awarded just over $1 million in funding from the FDA through their Orphan Drug Grant program to support this Phase II DMD clinical study. It is the first DMD clinical study approved for FDA Orphan Product Development funding.

Additional pilot studies of ifetroban are underway including several investigator-initiated trials. We are awaiting further study results before deciding on the best path for approval for ifetroban, our first new chemical entity.

New Hospital Product Candidate

Cumberland was responsible for the formulation, development and FDA approval of both Acetadote and Caldolor. Our Medical Advisory Board has helped us identify additional opportunities that address unmet or poorly met medical needs. As a result, Cumberland has successfully designed, formulated and completed the preclinical studies for a cholesterol reducing agent for use in the hospital setting.

During 2017, we completed a Phase I study which defined the pharmacokinetic properties and provided a favorable safety profile for this new product candidate. The study results and a proposed clinical development plan were discussed with the FDA and, as a result, a Phase II study has been initiated and progressed during 2019.

OUR STRATEGY

Our growth strategy involves maximizing the potential of our existing brands while continuing to build a portfolio of differentiated products. We currently market six FDA approved products for sale in the United States. Through our international partners, we are working to bring our products to patients in their countries. We also look for opportunities to expand our products into additional patient populations through clinical trials, new indications, and select investigator-initiated studies. We actively pursue opportunities to acquire additional marketed products as well as late-stage development product candidates in our target medical specialties. Our clinical team is developing a pipeline of new product candidates to address unmet medical needs. Further, we are supplementing these activities with the early stage drug development activities at CET, our majority-owned subsidiary. Specifically, we are seeking long term sustainable growth by executing the following plans:

Support and expand the use of our marketed products. We continue to evaluate our products following their FDA approval to determine if additional clinical data could expand their market and use. We will continue to explore opportunities for label expansion to bring our products to new patient populations. We have secured pediatric approval, expanding the labeling for both our Acetadote and Caldolor brands.

Selectively add complementary brands. In addition to our product development activities, we are also seeking to acquire products or late-stage development product candidates to continue to build a portfolio of complementary brands. We focus on under-promoted, FDA approved drugs as well as late-stage development products that address poorly met medical needs. We will continue to target product acquisition candidates that are competitively differentiated, have valuable intellectual property or other protective features, and allow us to leverage our existing infrastructure. Our acquisition of Vibativ represents our largest product acquisition.

Progress clinical pipeline and incubate future product opportunities at CET.We believe it is important to build a pipeline of innovative new product opportunities. Our ifetroban Phase II development programs represent the implementation of this strategy. At CET, we are supplementing our acquisition and late-stage development activities with the early-stage drug development activities. CET partners with universities and other research organizations to develop promising, early-stage product candidates, which Cumberland has the opportunity to further develop and commercialize. We expanded our network of university collaborations with the addition of Louisiana State University and the Medical University of South Carolina.

Leverage our infrastructure through co-promotion partnerships. We believe that our commercial infrastructure can help drive prescription volume and product sales. We look for strategic partners that can complement our capabilities and enhance the opportunity for our brands. Our co-promotion partnership with Poly Pharmaceuticals, Inc. allows us to expand current promotional support for Kristalose across the United States.

Build an international contribution to our business.We have established our own commercial capabilities, including two sales divisions to cover the U.S. market for our products. We are also building a network of select international partners to register our products and make them available to patients in their countries.

We will continue to develop and expand our network of international partners while supporting our partners' registration and commercialization efforts in their respective territories. The acquisition of Vibativ resulted in several new international partners and market opportunities.

Manage our operations with financial discipline.We continually work to manage our expenses in line with our revenues in order to deliver positive cash flow from operations. We remain in a strong financial position, with favorable gross margins, and a strong balance sheet. We use excess cash flow for our ongoing share repurchase program.

SALES AND MARKETING

Our sales and marketing team has broad industry experience in selling branded pharmaceuticals. Our sales and marketing professionals manage our dedicated hospital and gastroenterology sales forces, including approximately 50 sales representatives and district managers, direct our national marketing campaigns and maintain key national account relationships.

Hospital market:We promote Caldolor, Vaprisol, Acetadote, and Vibativ through our dedicated hospital sales division. This organization targets key hospitals across the U.S. and is comprised of sales professionals with substantial experience in the hospital market. Independent market data continues to indicate that the majority of pharmaceutical promotional spending is directed toward large, outpatient markets on drugs intended for chronic use rather than short-term, hospital use.

We believe the hospital market is under-served and highly concentrated, and that it can be penetrated effectively by a small, dedicated sales force without large-scale promotional activity. Our established position in the hospital market provided the rationale for adding Vibativ as our first infectious disease product that complement our hospital product line. Our strategy has been to increase the focus of our hospital sales team on targeted, high priority accounts.

Gastroenterology market:We promote Kristalose and Omeclamox-Pak through a dedicated field sales team addressing a targeted group of physicians who are large prescribers of both products. Because the market for gastrointestinal diseases is broad in patient scope, yet relatively narrow in physician base, we believe it provides product opportunities that can be penetrated with a modest sized sales force.

By investing in our sales and marketing activities we believe that we can increase market share for both products. Our field sales force features both Kristalose and Omeclamox-Pak during most of their physician calls, establishing our presence in the gastroenterology market.

Our marketing executives conduct ongoing analyses to evaluate marketing campaigns and promotional programs. The evaluations include development of product profiles, testing of the profiles against the needs of the market, determining what additional product information or development work is needed to effectively market the products and preparing financial forecasts.

We utilize professional branding and packaging as well as promotional items to support our products, including direct mail, sales brochures, journal advertising, educational and reminder leave-behinds, patient educational pieces, coupons, and product sampling. We also regularly attend select medical meetings and trade shows to expand the awareness of our products.

Our national accounts function is responsible for key large buyers and related marketing programs. National accounts maintains relationships with our wholesaler customers as well as with third-party payors such as group purchasing organizations, pharmacy benefit managers, hospital buying groups, state and federal government purchasers and health insurance companies.

MATERIAL CUSTOMERS

Our primary customers are wholesale pharmaceutical distributors in the United States. Total revenue by customer for each customer representing 10% or more of consolidated gross revenues are summarized below for the year ended December 31, 2019:

2019
Customer 1 26%
Customer 2 25%
Customer 3 16%
Customer 4 14%

INTERNATIONAL PARTNERSHIPS

We have established our own capabilities to support the commercialization of our products in the U.S. Our international strategy is to identify and partner with other companies that have the appropriate capabilities to support our products in their respective countries. We have entered into a series of agreements to establish an international network, which is summarized in the table below and includes information on our primary partners:

International Partner Product(s) Territory Status
Phebra Pty Ltd Acetadote Australia and New Zealand Marketed
DB Pharm Korea Co., Ltd. Caldolor Corea del Sud Marketed
Vibativ Registrazione
Seqirus (a CSL company) Caldolor Australia and New Zealand Marketed
Sandor Medicaids Pvt. Ltd. Caldolor India, Pakistan, Bangladesh and Nepal Marketed
GerminMED Caldolor Arabian Peninsula Marketed
PT. ETHICA Industri Farmasi Caldolor Indonesia Registrazione
Laboratorios Grifols, S.A. Caldolor Spain, Portugal and South America Registrazione
WinHealth Pharma Group Co. Caldolor & Acetadote China and Hong Kong Development
R-Pharm JSC Vibativ Russia Marketed
Hikma Pharmaceuticals Vibativ Arabian Peninsula Registrazione
SciClone Pharmaceuticals, Inc. Vibativ China and Hong Kong Registrazione
Dr. Reddy's Laboratories Vibativ India Registrazione

Our international commercialization agreements include a license to one or more Cumberland products for a specific territory as noted in the table above. We seek partners who have the local infrastructure to support the registration and commercialization of our products in their territory.

Under the terms of our agreements our partners are responsible for:

Seeking regulatory approvals for the products;

Launching the brand;

Managing the ongoing marketing, sales and product distribution;

Addressing the ongoing regulatory requirements in the international territories;

Remitting any upfront, regulatory and sales milestone payments;

Providing the transfer price for supplies of product; e

Calculating and paying any royalties, as applicable.

Our responsibilities include:

Providing a dossier of relevant information to support product registration;

Maintaining our intellectual property associated with the product;

Sharing our marketing strategy, experience and materials for the brand; e

Manufacturing and providing finished product for sale.

During 2019, we worked to support our existing international partners and to identify new companies to represent our products in select additional territories. We also continued to transition the Vibativ license arrangements for several international markets from Theravance.

CLINICAL AND REGULATORY AFFAIRS

We have in-house capabilities for the management of our clinical, professional and regulatory affairs. Our team develops and manages our clinical trials, prepares regulatory submissions, manages ongoing product-related regulatory responsibilities and manages our medical information call center. Team members have been responsible for devising the regulatory and clinical strategies for all our products as well as obtaining FDA approvals for Acetadote, Caldolor and RediTrex.

Clinical development

Our clinical development personnel are responsible for:

creating clinical development strategies;

designing, implementing and monitoring our clinical trials; e

creating case report forms and other study-related documents.

Regulatory and quality affairs

Our internal regulatory and quality affairs team is responsible for:

preparing and submitting INDs for clearance to begin patient studies;

preparing and submitting NDAs and fulfilling post-approval marketing commitments;

maintaining investigational and marketing applications through the submission of appropriate reports;

submitting supplemental applications for additional label indications, product line extensions and manufacturing improvements;

evaluating regulatory risk profiles for product acquisition candidates, including compliance with manufacturing, labeling, distribution and marketing regulations;

monitoring applicable third-party service providers for quality and compliance with current Good Manufacturing Practices ('GMPs'), Good Laboratory Practices ('GLPs'), and Good Clinical Practices ('GCPs'), and performing periodic audits of such vendors; e

maintaining systems for document control, product and process change control, customer complaint handling, product stability studies and annual drug product reviews.

PROFESSIONAL AND MEDICAL AFFAIRS

Our medical team provides in-house, medical information support for our marketed products. This includes interacting directly with healthcare professionals to address any product or medical inquiries through our medical information call center and medical science liaisons. In addition to coordinating the call center, our clinical/regulatory group generates medical information letters, provides informational memos to our sales forces and assists with ongoing training for the sales forces.

CLINICAL DEVELOPMENT AND STUDY RESULTS

Vibativ Clinical Manuscript

In October 2019, a new study was published revealing the superiority of Vibativ (telavancin) over vancomycin in select patients with bacterial pneumonia. Study results were published in Infectious Diseases and Therapy, and it showed numerically superior cure rates of telavancin compared to vancomycin within a subset of patients who were enrolled in phase 3 ATTAIN trials and had hospital-acquired pneumonia caused by bacteria with low susceptibility to vancomycin.

In November 2019, we announced another study, published online in Drugs – Real World Outcomes, detailing the positive clinical outcomes that resulted from treating multiple infection types with Vibativ, including complicated skin and skin structure infections, bone and joint infections, bacteremia and endocarditis, and lower respiratory tract infections.

Vibativ is a patented, FDA-approved injectable anti-infective for the treatment of certain serious bacterial infections including hospital-acquired and ventilator-associated bacterial pneumonia and complicated skin and skin structure infections. It addresses a range of Gram-positive bacterial pathogens, including those that are considered difficult-to-treat and multidrug-resistant. In November 2018, Cumberland reached an agreement to acquire Vibativ from Theravance Biopharma and assume global responsibility for the product.

Caldolor Pediatric Study

We previously received FDA approval for the use of Caldolor in pediatric patients six months of age and older. Caldolor is the first and only injectable non-steroidal anti-inflammatory drug (NSAID) approved for use in children. We then initiated a study to collect data on the use of Caldolor in children ranging in age from birth up to six months of age. Enrollment in that multi-center study was completed in 2019.

Ifetroban Phase II Studies

In September 2019, Cumberland announced the receival of FDA Orphan Drug Grant funding for a new Phase II clinical program. We initiated the clinical development of ifetroban for the treatment of cardiomyopathy associated with Duchenne Muscular Dystrophy (DMD). Based on preclinical findings, the FDA has cleared Cumberland's application to study ifetroban in DMD patients, seven years of age and older. In addition, Cumberland was awarded just over $1 million in funding from the FDA through their Orphan Drug Grant program to support this Phase II DMD clinical study. This study is the first DMD clinical study approved for FDA Orphan Product Development funding.

New Hospital Product Candidate Study

Cumberland was responsible for the formulation, development and FDA approval of both Acetadote and Caldolor. Our Medical Advisory Board has helped us identify additional opportunities that address unmet or poorly met medical needs. As a result, Cumberland has successfully designed, formulated and completed the preclinical studies for a cholesterol reducing agent for use in the hospital setting.

During 2017, we completed a Phase I study which defined the pharmacokinetic properties and provided a favorable safety profile for this new product candidate. The study results and a proposed clinical development plan were discussed with the FDA and, as a result, in 2018 a Phase II study was initiated, with enrollment continuing in 2019.

BUSINESS DEVELOPMENT

Since inception, we have had an active business development program focused on acquiring rights to marketed products and product candidates that fit our strategy and target markets. We source business development opportunities through our international network of advisory firms and individual pharmaceutical industry and medical advisors. A multi-disciplinary internal management team reviews these opportunities on a regular basis using a list of selection criteria. We have historically focused on product opportunities that are a strategic fit with our commercial organization, development expertise and medical focus, employing a variety of transaction structures.

We intend to continue to build a portfolio of complementary, niche products largely through product acquisitions and late-stage product development.

Our primary targets are under-promoted, FDA approved drugs with existing brand recognition and late-stage development product candidates that address unmet or poorly met medical needs in the hospital acute care and gastroenterology markets. We believe that by focusing mainly on approved or late-stage products, we can minimize the significant risk, cost and time associated with drug development.

Early in 2019, we announced a strategic review of our brands, capabilities, and international partners. This review followed an accelerated business development initiative, which resulted in a series of transactions. Because of that progress, we felt that it was prudent to take a fresh look at our product portfolio, partners, and organization to ensure proper focus and capabilities.

Expanded International Partners

As a result of our strategic review, we expanded our international arrangements through several new agreements.

We executed a License and Distribution agreement with HongKong WinHealth Pharma Group Co. Limited ('WinHealth') for our Caldolor and Acetadote brands in China and Hong Kong. We anticipate WinHealth will provide $2 million in milestone payments and up to an estimated $290 million in revenue contribution over a ten – year period for supplies of the products following their registration in China.

We also entered into a Strategic Alliance agreement with WinHealth to explore future business opportunities that will further the mission and goals of each organization. Founded in Hangzhou, China and currently headquartered in Hong Kong, WinHealth has developed a wide breadth of capabilities including drug licensing, product development and registration, and has established a strong network of distribution and sales promotional capabilities for the Chinese market. WinHealth has established partnerships with international companies that include Boehringer-Ingelheim, Janssen, Novartis, Pfizer, and Roche, generating approximately $330 million in annual sales in 2018.

Additionally, we completed the assignment and amendment of a Commercialization Agreement with R-Pharma JSC ('R Pharma') associated with ongoing distribution of Vibativ in Russia and a number of adjacent countries in Eastern Europe. R-Pharma is one of the leading multinational pharmaceutical organizations based in Russia. Headquartered in Moscow and focusing in a wide breadth of therapeutic areas in the specialty and hospital care markets, R-Pharma generated over $1.6 billion in revenues in 2018.

We completed the assignment and amendment of a Commercialization Agreement with Hikma Pharmaceuticals LLC ('Hikma') to register and distribute Vibativ in a number of countries throughout the Middle East. Hikma is a multinational pharmaceutical company currently headquartered in London, United Kingdom. Originally founded in Amman, Jordan the company now has market representation throughout the world, with a particular focus in the Middle East and North African regions. Hikma develops, manufactures, and markets a broad range of branded and non-branded generic medicines, generating over $2 billion in gross sales during 2018.

We also completed the assignment and amendment of a Commercialization Agreement with Dr. Reddy's Laboratories Limited ('Dr. Reddy's') for the registration and distribution of Vibativ in India. Dr. Reddy's is a multinational pharmaceutical company based in Hyderabad, India. The company currently markets over 190 medications through their commercial operations in over 35 countries. Combined with their extensive network of manufacturing capabilities, Dr. Reddy's generated over $2.2 billion in sales during their 2018 – 2019 fiscal year.

Poly Co-Promotion Agreement

During 2019, we extended our co-promotion arrangement with Poly Pharmaceuticals, Inc. ('Poly').

We originally entered into a co-promotion arrangement with Poly for our Kristalose product in 2017. Poly is a privately held U.S. specialty pharmaceutical company that is featuring Kristalose to an expanded number of physicians. Poly's sales organization is more than doubling the number of nationwide physicians that are reached with the Kristalose brand message.

Nordic License Agreement

In November 2016, we announced our agreement to acquire the exclusive U.S. rights to Nordic Group B.V.'s injectable methotrexate product line. The products are designed for the treatment of active rheumatoid arthritis, juvenile idiopathic arthritis, severe psoriatic arthritis, and severe disabling psoriasis.

The product line is approved for patient use in various European countries and received FDA approval near the end of 2019. Cumberland has registered and will commercialize the methotrexate products in the United States under the brand name RediTrex.

2R and Foxland Agreements

During 2018, we entered into another co-promotion arrangement related to our Kristalose product. We have agreements with 2R Investments, LLC and with Foxland Pharmaceuticals, Inc. to package, distribute and promote an authorized generic form of our Kristalose product to physician targets that we do not cover. Cumberland continues to manage the regulatory activities associated with the product.

Piramal Co-promotion Agreement

In November 2019, we concluded our co-promotion agreement with Piramal Critical Care ('Piramal').

Cumberland previously entered into a co-promotion agreement with Piramal in 2015. Through this agreement, Piramal co-promoted two of Cumberland's branded hospital products, Caldolor and Vaprisol throughout the United States.

Clinigen Strategic Dissolution Agreement

We previously entered into a strategic alliance with the Clinigen Group plc ('Clinigen'), an international specialty pharmaceutical and services company, to commercialize select Clinigen products in the U.S. In May 2016, we announced an agreement with Clinigen to acquire an exclusive license and commercialize Ethyol®in the U.S. We then announced in January 2017, our second agreement with Clinigen to acquire an exclusive license and launch Totect®in the U.S.

During May 2019, following a strategic review of our partners, products and organization, we entered into a Dissolution Agreement with Clinigen in which Cumberland will return the exclusive rights to commercialize Ethyol and Totect in the United States to Clinigen. Under the final terms of the amended Dissolution Agreement we transitioned from our current arrangement with Clinigen effective December 31, 2019. Under the terms of the agreement, Cumberland will no longer be involved directly or indirectly with the distribution, marketing and promotion of either Ethyol or Totect or any competing products. In exchange for the return of these product license rights and not competing with either product, we will receive $5 million in financial consideration paid over the two-years following December 31, 2019.

CET University Collaboration Agreements

In February 2019, CET and the technology transfer organization for the Medical University of South Carolina ('MUSC') entered into an agreement, adding to CET's roster of academic collaborations which also includes Vanderbilt University, the University of Mississippi, Louisiana State University and the University of Tennessee Research Foundation. Under the agreement, CET will evaluate MUSC discoveries, license intellectual property rights to promising technologies, and partner with MUSC research scientists to advance product development toward commercialization.

Through CET, we collaborate with a select group of academic research institutions located in the mid-south region of the U.S. to identify, co-develop and seek grant funding for promising biomedical technologies emerging from those research institutions.

These arrangements enable CET to team with university-based researchers to advance their scientific discoveries and breakthroughs by designing new product candidates to improve patient care and address unmet medical need.

MANUFACTURING AND DISTRIBUTION

Manufacturing

We partner with third parties for certain non-core, capital-intensive capabilities, including the manufacturing and distribution of our products. We manage these third-party relationships and are responsible for the quality review and release of each lot of our products.

Acetadote®

For Acetadote we have agreements with two manufacturers, and one manufacturer provided commercial supplies of the product during 2019.

Caldolor®

We have agreements with multiple manufacturers for the supply of Caldolor and during 2019 we obtained commercial supplies from three of these manufacturers for our international and domestic Caldolor requirements.

Kristalose®

We have an agreement for the purchase of Kristalose API with an international supplier. We also have manufacturing relationships with two packagers who provided finished supplies of the product for commercial and sampling purposes during 2019.

Omeclamox-Pak®

Prior to our asset purchase agreement with GEL that closed in December 2018, GEL managed the packaging and supply of Omeclamox-Pak commercial and sample units. Following our acquisition of the remaining rights to the brand in late 2018, we assumed responsibility for the packaging and supply of the product. During 2019 we entered into a new packaging arrangement for this product.

Vaprisol®

As part of the acquisition of Vaprisol, we purchased a significant existing supply of raw material inventory. In addition, as part of that transaction, we were assigned a commercial supply agreement with the historical Vaprisol manufacturer. In 2018, the manufacturer informed us that they would no longer be able to provide the product following the manufacturing of one final batch which is expected to provide us with a multi-year supply. Therefore, we are evaluating alternatives for a new manufacturer to provide us with long term supplies of the product.

Vibativ®

Through our acquisition of Vibativ, we acquired a multi-year supply of raw material, work in process and finished goods inventory. As a result of the agreement, we are now responsible for the future manufacture of the product and completed the transfer of the product's manufacturing activities to a new supplier in 2019.

RediTrex®

Under our agreement with Nordic, they will be responsible for providing us the packaged and labeled commercial supply of the RediTrex product.

Ethyol®

As part of the Ethyol agreement, during 2019 Clinigen was responsible for the supply of the product and has provided commercial inventory for Cumberland to package and distribute.

Totect®

Under our Totect agreement, during 2019 Clinigen was also responsible for overseeing the manufacture of the product and has provided commercial supplies for us to package and distribute.

Distribution

Like many pharmaceutical companies, we engage a third-party with appropriate facilities and logistical expertise to support the U.S. distribution of our products. Cardinal Health has exclusively handled our U.S. product logistics activities, including warehousing, shipping, and various other customer activities. Our primary customers are the wholesalers of pharmaceuticals who provide our products to hospitals, clinics and retail pharmacies in the U.S.

CORPORATE DEVELOPMENT

Cumberland Foundation

In December 2017, we formed the Cumberland Pharma Foundation (the 'Foundation') to serve as a vehicle to facilitate the ongoing philanthropic endeavors of Cumberland Pharmaceuticals Inc.

The Foundation was formed as an independent, nonprofit corporation designed to qualify as a tax-exempt organization pursuant to Section 501(a) of the Internal Revenue Code. The Foundation's Board of Directors is comprised of Cumberland Pharmaceuticals executives who are responsible for overseeing the Foundation's ongoing activities including charitable contributions.

During 2018, we provided a grant of 50,000 shares of our common stock to the Foundation. The shares will address the ongoing financial needs of the Foundation, with most of the shares expected to be held for the opportunity to realize long term appreciation to support the Foundation's future. The Foundation maintains independent financial statements and its contributions will not impact the financial statements of Cumberland Pharmaceuticals. Initial annual grants by the Foundation have been and remain consistent with the historic level of contributions made by Cumberland Pharmaceuticals. During 2019, we committed approximately $50,000 in cash contributions to be paid to the Foundation during 2020.

Cumberland Health and Wellness Political Action Committee

In November 2017 we formed the Cumberland Health and Wellness Political Action Committee (PAC). The objective of the PAC is to support candidates and policies that are consistent with Cumberland's mission of advancing patient care. The PAC's activities will be at the local, state and federal level and conducted in a bi-partisan manner. The initial committee membership is comprised of Cumberland Pharmaceuticals employees. The PAC received initial funding from us and future funding will include voluntary individual contributions from Cumberland Pharmaceuticals directors and employees.

SUBSEQUENT EVENTS

Next Generation Caldolor Product

In January 2020, we launched the next generation of our Caldolor (ibuprofen) Injection product. This formulation of Caldolor comes in a ready-to-use bag that may be administered without dilution for pain relief. This launch follows FDA approval in 2019 of the product's new delivery method.

A non-steroidal anti-inflammatory drug (NSAID), Caldolor may be used as the sole method of treatment for mild-moderate pain or as part of a multi-modal treatment for severe pain. The new formulation of Caldolor comes in a pre-mixed bag containing 800 mg of ibuprofen in a 200 mL patented low sodium formulation for injection that is ready to use. It is the first and only FDA-approved pre-mixed bag of ibuprofen. Caldolor is still available as an 800 mg/8mL single-dose vial (100mg/mL) for dilution in addition to the ready-to-use bag (4 mg/mL). The new, premixed presentation provides healthcare professionals a formulation that is easy to administer, helping manage the treatment of patient pain and fever, while reducing opioid consumption.

PATENTS, TRADEMARKS AND OTHER INTELLECTUAL PROPRIETARY RIGHTS

We own the trademarks for each of our branded pharmaceutical products as well as for our corporate name and logo. We have applied for trademark registration for other various names and logos. Over time, we intend to maintain registrations on trademarks that remain valuable to our business.

We seek to protect our products from competition through a combination of patents, trademarks, trade secrets, FDA exclusivity and contractual restrictions on disclosure. Proprietary rights, including patents, are an important element of our business. We seek to protect our proprietary information by requiring our employees, consultants, contractors and other advisors to execute agreements providing for protection of our confidential information upon commencement of their employment or engagement. We also require confidentiality agreements from entities to which we provide our confidential information or materials.

Acetadote®

We developed a new formulation of Acetadote (acetylcysteine) Injection as part of a Phase IV commitment in response to a request by the FDA to evaluate the reduction of ethylene diamine tetraacetic acid ('EDTA') from the product's formulation. In April 2012, the USPTO issued U.S. Patent number 8,148,356 (the '356 Acetadote Patent') which is assigned to us. The claims of the 356 Acetadote Patent encompass the new Acetadote formulation and include composition of matter claims. Following its issuance, the 356 Acetadote Patent was listed in the FDA Orange Book. The 356 Acetadote Patent is scheduled to expire in May 2026, which time period includes a 270-day patent term adjustment granted by the USPTO.

Following the issuance of the 356 Acetadote Patent, we received separate Paragraph IV certification notices from InnoPharma, Inc. ('InnoPharma'), Paddock Laboratories, LLC ('Paddock'), Mylan Institutional LLC ('Mylan'), Sagent Agila LLC ('Sagent') and Perrigo Company ('Perrigo') challenging the 356 Acetadote Patent on the basis of non-infringement and/or invalidity. We responded by filing five separate infringement lawsuits, in the appropriate United States District Courts, to contest each of the challenges.

On November 12, 2012, we entered into a Settlement Agreement (the 'Settlement Agreement') with Paddock and Perrigo to resolve the challenges and the pending litigation with those two companies.

On November 1, 2013, the United States District Court filed opinions granting Sagent's and InnoPharma's motions to dismiss our suits and we agreed not to file an appeal or motion to reconsider, thereby resolving the challenges and the pending litigation with those two companies.

Under the Settlement Agreement, Paddock and Perrigo admit that the 356 Acetadote Patent is valid and enforceable and that any Paddock or Perrigo generic version of Acetadote (with or without EDTA) would infringe upon the 356 Acetadote Patent. In addition, Paddock and Perrigo will not challenge the validity, enforceability, ownership or patentability of the 356 Acetadote Patent through its expiration currently scheduled for May 2026. On

November 12, 2012, in connection with the execution of the Settlement Agreement, we entered into a License and Supply Agreement with Paddock and Perrigo (the 'License and Supply Agreement').

Under the terms of the License and Supply Agreement, if a third party receives final approval from the FDA for an ANDA to sell a generic Acetadote product and such third party made such generic version available for purchase in commercial quantities in the United States, we are to supply Perrigo with an Authorized Generic version of our Acetadote product.

On May 18, 2012, we also submitted a Citizen Petition to the FDA requesting that the FDA refrain from approving any applications for acetylcysteine injection that contain EDTA, based in part on the FDA's request that we evaluate the reduction or removal of EDTA from our original Acetadote formulation.

On November 7, 2012, the FDA responded to the Citizen Petition denying our request and on November 8, 2012, we learned that the FDA approved the ANDA referencing Acetadote filed by InnoPharma, Inc. We brought suit against the FDA contesting the FDA's decision to approve the InnoPharma generic on November 13, 2012.

On September 30, 2013, the United States District Court filed an opinion granting a summary judgment in favor of the FDA regarding this suit.

As noted above, during 2012 the FDA approved the ANDA referencing Acetadote filed by InnoPharma, Inc. Upon this condition, in accordance with the License and Supply agreement with Perrigo, we began to supply Perrigo with our Authorized Generic. On January 7, 2013, Perrigo announced initial distribution of our Authorized Generic acetylcysteine injection product.

On March 19, 2013, the USPTO issued U.S. Patent number 8,399,445 (the '445 Acetadote Patent') which is assigned to us. The claims of the 445 Acetadote Patent encompass the use of the 200 mg/ml Acetadote formulation to treat patients with acetaminophen overdose. On April 8, 2013, the 445 Acetadote Patent was listed in the FDA Orange Book. The 445 Acetadote Patent is scheduled to expire in August 2025. Following the issuance of the 445 Acetadote Patent we received separate Paragraph IV certification notices from Perrigo, Sagent Pharmaceuticals, Inc., and Mylan challenging the 445 Acetadote Patent on the basis of non-infringement, unenforceability and/or invalidity.

On June 10, 2013, we became aware of a Paragraph IV certification notice from Akorn, Inc. challenging the 445 Acetadote Patent and the 356 Acetadote Patent on the basis of non-infringement. On July 12, 2013, we filed a lawsuit for infringement of the 356 Acetadote Patent against Akorn, Inc. in United States District Court.

On February 18, 2014, the USPTO issued U.S. Patent number 8,653,061 (the '061 Acetadote Patent') which is assigned to us. The claims of the 061 Acetadote Patent encompass the use of the 200 mg/ml Acetadote formulation to treat patients with acetaminophen overdose. Following its issuance, the 061 Acetadote Patent was listed in the FDA Orange Book. The 061 Acetadote Patent is scheduled to expire in August 2025.

On May 13, 2014, the USPTO issued U.S. Patent number 8,722,738 (the '738 Acetadote Patent') which is assigned to us. The claims of the 738 Acetadote Patent encompass administration methods of acetylcysteine injection, without specification of the presence or lack of EDTA in the injection. Following its issuance, the 738 Acetadote Patent was listed in the FDA Orange Book and it is scheduled to expire in April 2032.

On December 11, 2014 and March 3, 2015, we became aware of Paragraph IV certification notices from Aurobindo Pharma Limited and Zydus Pharmaceuticals (USA) Inc., respectively, challenging the 356, 445, 061, and 738 Acetadote Patents on the basis of non-infringement.

On February 10, 2015, the USPTO issued U.S. Patent number 8,952,065 (the '065 Acetadote Patent') which is assigned to us. The claims of the 065 Acetadote Patent encompass the use of the 200 mg/ml Acetadote formulation to treat patients with acute liver failure. The 065 Acetadote Patent is scheduled to expire in August 2025.

On September 30, 2015, the United States District Court for the Northern District of Illinois, Eastern Division ('District Court') ruled in our favor in our lawsuit against Mylan for infringement of the 445 Acetadote Patent. The opinion upheld our 445 Acetadote Patent and expressly rejected Mylan's validity challenge. The District Court

ruled that Mylan is liable to us for infringement of the 445 Acetadote patent in light of Mylan's Abbreviated New Drug Application in which Mylan sought to market a generic version of Acetadote.

On November 17, 2015, the District Court entered an order enjoining Mylan and its affiliates from selling or using its generic version of Acetadote until August 2025, the date of expiration of the 445 Acetadote Patent. On October 30, 2015, Mylan filed a notice of appeal to the U.S. Court of Appeals for the Federal Circuit (the 'Appeals Court').

On May 3, 2016, the USPTO issued U.S. Patent number 9,327,028 (the '028 Acetadote Patent') which is assigned to us. The claims of the 028 Acetadote Patent encompass administration methods of acetylcysteine injection, without specification of the presence or lack of EDTA in the injection. Following its issuance, the 028 Acetadote Patent was listed in the FDA Orange Book and it is scheduled to expire in July 2031.

On January 26, 2017, the Appeals Court affirmed the District Court ruling in our favor in our lawsuit against Mylan for infringement of the 445 Acetadote Patent. The Appeals Court opinion affirmed the District Court's ruling upholding our 445 Acetadote Patent and expressly rejected Mylan's validity challenge.

On November 3, 2017, we became aware of a Paragraph IV certification notice from Exela Pharma Sciences, LLC challenging the 356, 445, 061, 738, and 028 Acetadote Patents on the basis of non-infringement.

We are considering our legal options and intend to continue to vigorously defend and protect our Acetadote product and related intellectual property rights.

Caldolor®

We are the owner of U.S. Patent No. 6,727,286, which encompasses ibuprofen solution formulations, methods of making the same, and methods of using the same, and which is scheduled to expire in November 2021. This U.S. patent is listed in the FDA Orange Book and is associated with our completed international application No. PCT/US01/42894. We have filed for international patent protection in association with this PCT application in various countries, several of which have been allowed.

We have an exclusive, worldwide license to clinical data for intravenous ibuprofen from Vanderbilt University, in consideration for royalty obligations related to Caldolor. During 2014, we obtained additional patents for the brand. On May 27, 2014, the USPTO issued U.S. Patent number 8,735,452 (the '452 Caldolor Patent') which is assigned to us. The claims of the 452 Caldolor Patent encompass methods of treating pain using intravenous ibuprofen. Following its issuance, the 452 Caldolor Patent was listed in the FDA Orange Book and is scheduled to expire in September 2029.

On October 28, 2014, the USPTO issued U.S. Patent number 8,871,810 (the '810 Caldolor Patent') which is assigned to us. The claims of the 810 Caldolor Patent encompass methods of treating pain using intravenous ibuprofen. Following its issuance, the 810 Caldolor Patent was listed in the FDA Orange Book and is scheduled to expire in September 2029.

During the third quarter of 2015, we obtained four additional patents for Caldolor. On July 7, 2015, the USPTO issued U.S. Patent number's 9,072,710 (the '710 Caldolor Patent') and 9,072,661 (the '661 Caldolor Patent') which are assigned to us. The claims of the 710 Caldolor Patent and the 661 Caldolor Patent include composition and methods of treating pain, inflammation and fever using intravenous ibuprofen. These Caldolor Patents are listed in the FDA Orange Book and are scheduled to expire in March 2032. On April 21, 2015, the USPTO issued U.S. Patent No. 9,012,508 (the '508 Caldolor Patent') which is assigned to us. The claims of the 508 Caldolor Patent include methods of treating pain using intravenous ibuprofen. Following its issuance, the 508 Caldolor Patent was listed in the FDA Orange Book and is scheduled to expire in September 2030. On August 25, 2015, the USPTO issued U.S. Patent number 9,114,068 (the '068 Caldolor Patent') which is assigned to us. The claims of the 068 Caldolor Patent include methods of treating pain using intravenous ibuprofen.

Following its issuance, the 068 Caldolor Patent was listed in the FDA Orange Book and is scheduled to expire in September 2029. On September 22, 2015, the USPTO issued U.S. Patent number 9,138,404 (the '404 Caldolor Patent') which is assigned to us. The claims of the 404 Caldolor Patent include methods of treating pain in critically

ill patients with intravenous ibuprofen. Following its issuance, the 404 Caldolor Patent was listed in the FDA Orange Book and is scheduled to expire in September 2029.

On March 29, 2016, the USPTO issued U.S. Patent number 9,295,639 (the '639 Caldolor Patent') which is assigned to us. The claims of the 639 Caldolor Patent include methods of treating pain in critically ill patients with intravenous ibuprofen. Following its issuance, the 639 Caldolor Patent was listed in the FDA Orange Book and is scheduled to expire in September 2029.

On May 16, 2017, the USPTO issued U.S. Patent number 9,649,284 (the '284 Caldolor Patent') which is assigned to us. The claims of the 284 Caldolor Patent include methods of treating pain in critically ill patients with intravenous ibuprofen. Following its issuance, the 284 Caldolor Patent was listed in the FDA Orange Book and is scheduled to expire in September 2029. We also have additional patent applications related to Caldolor which are pending with the USPTO.

Vaprisol®

We own numerous U.S. patents and related international patents for Vaprisol. These patents were acquired in our February 2014 acquisition of certain product rights, intellectual property and related assets of Vaprisol from Astellas.

Vibativ®

We own numerous U.S. patents and related international patents for Vibativ. These patents were acquired in our November 2018 acquisition of certain product rights, intellectual property and related assets of Vibativ from Theravance. Eleven Vibativ patents are listed in the FDA Orange Book. U.S. Patent number 7,531,623 (the '623 Vibativ Patent') is scheduled to expire in January 2027 and includes composition of matter claims that encompass the Vibativ drug substance as well as methods for preparing the Vibativ drug substance.

Remaining Products

We have no issued patents for our RediTrex, Omeclamox-Pak and Kristalose products. We have patent applications relating to our ifetroban products pending with the USPTO.

COMPETITION

The pharmaceutical industry is characterized by intense competition and rapid innovation. Our continued success in developing and commercializing pharmaceutical products will depend, in part, upon our ability to compete against existing and future products in our target markets. Competitive factors directly affecting our markets include but are not limited to:

product attributes such as efficacy, safety, ease-of-use and cost-effectiveness;

brand awareness and recognition driven by sales, marketing and distribution capabilities;

intellectual property and other exclusivity rights;

availability of resources to build and maintain developmental and commercial capabilities;

successful business development activities;

extent of third-party reimbursements; e

establishment of advantageous collaborations to conduct development, manufacturing or commercialization efforts.

A number of our competitors possess research and development and sales and marketing capabilities as well as financial resources greater than ours. These competitors, in addition to emerging companies and academic research institutions, may be developing, or in the future could develop, new technologies that could compete with our current and future products or render our products obsolete.

Our products face competition from other branded products, generics, and alternate medical treatments. Our task is to position each brand to feature its competitive advantages, implement a well thought out marketing plan and provide focused sales and other tactical support.

Acetadote®

Acetadote is our injectable formulation of NAC for the treatment of acetaminophen overdose. NAC is accepted worldwide as the standard of care for acetaminophen overdose. Our competitors in the acetaminophen overdose market are those companies selling orally administered NAC including, but not limited to, Geneva Pharmaceuticals, Inc., Bedford Laboratories division of Hikma Pharnaceuticals, Roxane Laboratories, Inc., InnoPharma Inc. and Hospira Inc.

In November 2012, InnoPharma Inc. was granted approval by the FDA to distribute their generic form of the old formulation of Acetadote containing EDTA. In late 2012, we entered into the Settlement Agreement with Paddock and Perrigo that included the right to distribute our Authorized Generic Acetadote injection product. Our branded Acetadote now competes with both the EDTA free Authorized Generic Acetadote distributed by Paddock and Perrigo along with generic Acetadote products that contain EDTA.

Manufactures of the old Acetadote formulation included: Akorn, AuroMedics Pharma, Fresenius Kabi and Sagent Pharmaceticals.

Caldolor®

Caldolor is marketed for the treatment of pain and fever, primarily in a hospital setting. A variety of other products address the acute pain market:

Morphine, the most commonly used product for the treatment of acute, post-operative pain, is manufactured and distributed by several generic pharmaceutical companies;

Other generic injectable opioids, including fentanyl, meperidine and hydromorphone, address this market;

Ketorolac tromethamine (brand name Toradol®), an injectable NSAID, is also manufactured and distributed by several generic pharmaceutical companies;

IV acetaminophen (brand name Ofirmev®), an injectable analgesic product is sold by Mallinckrodt plc;

Bupivicaine injectable suspension (brand name Exparel®), pproduct sold by Pacira Pharmaceuticals, Inc.; e

IV meloxicam (brand name Anjeso™), a once a day injectable COX-2 prefential NSAID manufactured by Baudax Bio which was recently approved by the FDA.

We are aware of other product candidates in development to treat acute pain including injectable NSAIDs, novel opioids, new formulations of existing therapies and extended release anesthetics. We believe non-narcotic analgesics for the treatment of post-surgical pain are the primary potential competitors to Caldolor.

In addition to the injectable analgesic products above, many companies are developing analgesics for specific indications such as migraine and neuropathic pain, oral extended-release forms of existing narcotic and non-narcotic products, and products with new methods of delivery such as transdermal. We are not aware of any approved injectable products indicated for the treatment of fever in the U.S. other than Caldolor and Ofirmev.

There are, however, numerous drugs available to physicians to reduce fevers in hospital settings via oral administration to the patient, including ibuprofen, acetaminophen, and aspirin. These drugs are manufactured by numerous pharmaceutical companies.

Kristalose®

Kristalose is a dry powder crystalline prescription formulation of lactulose indicated for the treatment of constipation. The U.S. constipation therapy market includes various prescription and over the counter, or OTC, products. The prescription products which we believe are our primary competitors are:

Lubiproston (brand name Amitiza®), an oral product indicated for the treatment of chronic idiopathic constipation, irritable bowel syndrome with constipation in adults, is manufactured and sold by Mallinckrodt Pharmaceuticals;

Naloxegol (brand name Movantik®), an oral product indicated for the treatment of opioid-induced constipation in adults with chronic non-cancer pain and recently acquired by RedHill Biopharma in the first quarter of 2020

Linaclotide (brand name Linzess®), an oral product indicated for the treatment of irritable bowel syndrome with constipation and chronic idiopathic constipation. It is sold by Allergan, Inc. and Ironwood Pharmaceuticals, Inc;

Plecanatide (brand name Trulance®), an oral product indicated for the treatment of irritable bowel syndrome with constipation and chronic idiopathic constipation. It is sold by Synergy Pharmaceuticals;

Generic and branded liquid lactulose products are marketed by a number of pharmaceutical companies; e

Lactitol for oral solution (brand name Pizensy), an oral, osmotic laxative indicated for the treatment of chronic idiopathic constipation and distributed by Braintree Laboratories, Inc. was recently approved by the FDA.

There are several hundred OTC products used to treat constipation marketed by numerous pharmaceutical and consumer health companies. MiraLax (polyethylene glycol 3350), previously a prescription product, was indicated for the treatment of constipation and manufactured and marketed by Bayer. MiraLax was converted to an OTC product in February 2007 and recently, the FDA rescinded the approval of the generic prescription polyethylene glycol 3350 products.

Omeclamox®-Pak

Omeclamox-Pak is a branded prescription product used for the treatment of Helicobacter pylori (H. pylori) infection and duodenal ulcer disease. It combines three well-known and widely prescribed medications packaged in a daily dosepack for patient convenience: omeprazole, clarithromycin, and amoxicillin. The three individual components of Omeclamox-Pak are also available from other suppliers through three separate prescriptions.

While there are several competitor products, Omeclamox-Pak is one of the two actively marketed products for this condition. In addition, compared to the competing products, Omeclamox-Pak has the lowest pill burden, fewest days of therapy and convenient twice daily dosing. The prescription combination products, indicated for treatment of H. pylori, which we believe are our primary competitors are:

PrevPac®, an oral product sold by Takeda Pharmaceutical Company. There are also approved generic versions of PrevPac;

Pylera®, an oral product manufactured and sold by Allergan plc; e

Talicia®, an oral product manufactured by RedHill Biopharma which was recently approved by the FDA.

Vaprisol®

Vaprisol is a patented, prescription brand indicated to raise serum sodium levels in hospitalized patients with euvolemic and hypervolemic hyponatremia. The product was developed and registered by Astellas and then launched in 2006. It is one of two branded prescription products indicated for the treatment of hyponatremia, and the first and only intravenously administered branded treatment. The other competing product is Samsca, an oral product sold by Otsuka Pharmaceutical Company.

Vibativ®

Effective November 12, 2018, Cumberland acquired the worldwide rights to Vibativ (telavancin) from Theravance Biopharma.

Vibativ is a potent, once-daily, injectable antibiotic for the treatment of certain gram-positive infections. Vibativ is approved for the treatment of complicated skin and skin structure infections and hospital-acquired or ventilator-associated bacterial pneumonia caused by susceptible isolates of Staphylococcus aureus when alternative treatments are not suitable. There are several generic and branded antibiotics that compete for these indications.

The major generic competitors are vancomycin, linezolid, and daptomycin. Vancomycin is by far the most widely used agent. Newer branded agents are also available including:

Ceftaroline fosamil (brand name Teflaro®) an injectable antibiotic manufactured and sold by Allergan

Dalbavancine (brand name Dalvance®), an injectable antibiotic manufactured and sold by Allergan

Oritavancin (brand name Orbactiv®), an injectable antibiotic manufactured and sold by Melinta

We are aware of a number of other novel antibiotics which are currently in development.

Antibiotic drug selection is based both on an empiric and susceptibility proven basis. In the hospital setting, cost is an important factor which favors the use of generic agents as long as they are effective. Newer agents are often reserved for two reasons: they are valuable in the treatment of patients that fail to respond to generics and it is considered good practice to conserve the use of these agents to reduce the risk of resistance.

GOVERNMENT REGULATION

The development of new pharmaceutical products can be a long, expensive and risky process. There is no assurance we will obtain successful study results or secure the needed market approvals for our pipeline product candidates. Governmental authorities in the U.S. and other countries extensively regulate the research, development, testing, manufacturing, distribution, marketing and sale of pharmaceutical products. In the U.S., the Food and Drug Administration ('FDA') under the Federal Food, Drug, and Cosmetic Act, ('FDCA'), the Public Health Service Act, and other federal statutes and regulations, subjects pharmaceutical products to rigorous review. Failure to comply with applicable U.S. requirements may subject a company to a variety of administrative or judicial sanctions, such as FDA refusal to approve pending New Drug Application ('NDAs') or biologics license applications, ('BLAs'), warning letters, product recalls, product seizures, total or partial suspension of production or distribution, injunctions, fines, civil penalties, and criminal prosecution.

We, our manufacturers and contract research organizations may also be subject to regulations under other federal, state and local laws, including the Occupational Safety and Health Act, (OSHA), the Resource Conservation and Recovery Act, the Clean Air Act and import, export and customs regulations as well as the laws and regulations of other countries.

FDA Approval Process

The FDA is a regulatory agency within the Department of Health and Human Services. A key responsibility is to regulate the safety and effectiveness of drugs sold in the United States. The FDA manages this responsibility into two phases: pre-approval (premarket) and post approval (post market). The FDA reviews manufacturers' applications to market drugs in the United States; a drug may not be sold unless it has FDA approval. The FDA continues its oversight of drug safety and effectiveness as long as the drug is on the market.

To market a prescription drug in the United States, a manufacturer needs FDA approval. To get that approval, the manufacturer must demonstrate the drug's safety and effectiveness according to criteria specified in law and agency regulations, ensure that its manufacturing plant passes FDA inspection, and obtain FDA approval for the drug's labeling, a term that includes all written material about the drug, including, for example, packaging, prescribing information for physicians and patient brochures.

The progression to drug approval begins before FDA involvement. First, scientists work in the laboratory to discover and develop a new compound. Next, basic questions on safety are answered by nonclinical testing with animals and then, a drug or biotechnology company develops a prototype drug. That company must seek clearance from the FDA by way of an Investigational New Drug ('IND') application to test the product with human subjects. Those tests, called clinical trials, are carried out sequentially in Phase I, II, and III studies, which involve increasing numbers of subjects. The manufacturer then compiles the resulting data and analyses in an NDA. The FDA reviews the NDA with three major concerns: (1) safety and effectiveness in the drug's proposed use; (2) appropriateness of the proposed labeling; and (3) adequacy of manufacturing methods to assure the drug's identity, strength, quality, and purity.

The FDCA and associated regulations detail the requirements at each step. The FDA uses a few special mechanisms to expedite drug development and the review process when a drug might address an unmet need or a serious disease or condition. Those mechanisms include accelerated approval, fast track and priority reviews and the newer designation, breakthrough therapy.

The sponsor of the drug typically conducts human clinical trials in three sequential phases, but the phases may overlap. Phase I clinical trials are generally conducted in a small number of healthy volunteers, primarily to collect and assess pharmacokinetics and safety data at one or more dosages prior to proceeding into patients.

In Phase II clinical trials, the sponsor evaluates the early efficacy of the product in short term trials on the targeted indication and identifies possible adverse effects and safety risks in a patient population.

Phase III clinical trials typically involve testing for patients in long term trials examining safety and clinical efficacy in an expanded population at geographically-dispersed test sites.

The FDA requires that clinical trials be conducted in accordance with the FDA's Good Clinical Practice GCP requirements. The FDA may order the partial, temporary or permanent discontinuation of a clinical trial at any time or impose other sanctions if it believes that the clinical trial is not being conducted in accordance with FDA requirements or presents an unacceptable risk to the clinical trial patients. The institutional review board ('IRB'), or ethics committee (outside of the U.S.), of each clinical site generally must approve the clinical trial design and patient informed consent and may also require the clinical trial at that site to be halted, either temporarily or permanently, for failure to comply with the IRB's requirements, or may impose other conditions.

The results of the nonclinical and clinical trials, together with detailed information on the manufacturing and composition of the product and proposed labeling, are submitted to the FDA in the form of an NDA for marketing approval. The NDA undergoes a 60-day validation review period before it is accepted for filing.

If the NDA is found to be incomplete, it will not be accepted. Once the NDA is validated and accepted for filing, the FDA begins an in-depth review of the NDA.

Under policies agreed to by the FDA under the Prescription Drug User Fee Act, or PDUFA (currently PDUFA VI – effective October 1, 2017), the FDA has a target timeline of 10 months in which to complete its initial review of

a standard NDA and respond to the applicant. The review process and the PDUFA goal date may be extended by two months to address deficiencies, or by three months if the FDA requests or the NDA sponsor otherwise provides additional information or clarification regarding information already provided in the submission at any time during the review clock period. If the FDA's evaluations of the NDA and the clinical and manufacturing procedures and facilities are favorable and meet all regulations, the FDA will issue an approval letter. Priority Review is reserved for drugs that represent a 'significant improvement in safety or efficacy' over existing treatments and FDA endeavors to complete these reviews in six months.

If the NDA meets with FDA approval, a letter will be sent out indicating approval and final labeling recommendations. If not, a Complete Response letter will be sent to applicants indicating that the review cycle for an application is complete and that the application is not ready for approval.

The complete response letter will describe the specific deficiencies that the agency has identified in an application and what changes must be made before the application can be approved, with no implication regarding whether the application will ultimately be approved. An approval letter authorizes commercial marketing of the drug for the proposed indication(s) under study. FDA reported that NDAs showed a steadier increase with the percentage of first-cycle approval letters for new molecular entities rising from 31% for FY 2000 applications to 91% for FY 2017 applications. The time and cost of completing these steps and obtaining FDA approval can vary dramatically depending on the drug. However, to complete these steps for a novel drug can take many years and cost millions of dollars.

Section 505(b) New Drug Applications

An NDA may be submitted under different methods, a 505(b)(1), 505(b)(2) or 505(j). Section 505(b) provides for the submission of an NDA to support the approval of a drug. Upon approval, a drug may be marketed only for the FDA-approved indication(s) in the approved dosage form. Further clinical trials may be necessary to gain approval for the use of the product for any additional indications or dosage forms.

The FDA also requires post market safety surveillance reporting to monitor the side effects of the drug, which may result in withdrawal of approval after marketing begins.

Section 505(b)(1) or the 'full' NDA is used for new chemical entities ('NCEs') and requires full clinical and nonclinical development of a compound. Marketing exclusivity assigned to a 505(b)(1) approval is five years. A 505(b)(2) NDA permits the submission of an NDA where at least some of the information required for approval comes from studies not conducted by or for the applicant using previously reported safety and efficacy data, and for which the applicant has not obtained a right of reference. Generally new studies are required to provide data on the proposed change.

Some examples of products that may be allowed to follow a 505(b)(2) path to approval are drugs which have a new dosage form, strength, route of administration, formulation or indication or combination drugs. Marketing exclusivity for a 505(b)(2) submission is three years.

Both 505 (b)(1) and (b)(2) are eligible for seven years of exclusivity for orphan drugs and/or six months for pediatric exclusivity. Any marketing exclusivity is independent of patent exclusivity. We successfully secured FDA approvals for Acetadote in January 2004, for Caldolor in June 2009 and for RediTrex in 2019 pursuant to the 505(b)(2) pathway.

Orphan drug designation

The Orphan Drug Act of 1983, ('Orphan Drug Act'), encourages manufacturers to seek approval of products intended to treat 'rare diseases and conditions' with a prevalence of fewer than 200,000 patients in the U.S. or for which there is no reasonable expectation of recovering the development costs for the product. For products that receive orphan drug designation by the FDA, the Orphan Drug Act provides tax credits for clinical research, FDA assistance with protocol design, eligibility for FDA grants to fund clinical studies, waiver of the FDA application fee, and a period of seven years of marketing exclusivity for the product following FDA marketing approval.

Acetadote received Orphan Drug designation in October 2001 and in 2004 the FDA approved the product to prevent or lessen hepatic injury after ingestion of a potentially hepatotoxic quantity of acetaminophen. Acetadote was entitled to marketing exclusivity until January 2011 for the treatment of this approved indication.

Section 505(j) abbreviated new drug applications

An ANDA is a type of NDA where approval of a generic drug is based on demonstrating comparability to an innovator drug product (the RLD or Reference Listed Drug). Applications are 'abbreviated' because they generally don't include preclinical and clinical data to establish safety and effectiveness. Generics must demonstrate that the product is bioequivalent (i.e., performs in the same manner and is comparable to the 'innovator' product in active ingredient, dosage form, strength, route of administration, labeling, quality, performance characteristics and intended use). Abbreviated applications may be submitted for drug products that are the same as a listed drug and must be identical in active ingredient(s), form, strength, route of administration, and identical in conditions of use (non-exclusive uses). Products are declared suitable based on a suitability petition to the FDA. If the petition is approved, the Sponsor may then submit the ANDA.

The Hatch-Waxman Act

The Drug Price Competition and Patent Term Restoration Act, informally known as the 'Hatch-Waxman Act', is a 1984 United States federal law which established the modern system of generic drugs.

Hatch-Waxman amended the Federal Food, Drug, and Cosmetic Act. Section 505(j) 21 U.S.C. 355(j) sets forth the process by which would-be marketers of generic drugs can file ANDAs to seek FDA approval of the generic. Section 505(j)(2)(A)(vii)(IV), the so-called Paragraph IV, allows 180-day exclusivity to companies that are the 'first-to-file' an ANDA against holders of patents for branded counterparts.

Hatch-Waxman Amendments grant generic manufacturers the ability to mount a validity challenge without incurring the cost of entry or risking enormous damages flowing from any possible infringement. Hatch-Waxman essentially redistributes the relative risk assessments and explains the flow of settlement funds and their magnitude. Hatch-Waxman gives generics considerable leverage in patent litigation.

Health care legislation

On March 23, 2010, President Obama signed into law the Patient Protection and Affordable Care Act, or PPACA. On March 30, 2010, the Health Care and Education Reconciliation Act of 2010, or HCERA, was enacted into law, which modified the revenue provisions of the PPACA. The PPACA as amended by the HCERA constitutes the healthcare reform legislation. The following highlights certain provisions of the legislation that may affect us.

Pharmaceutical Industry Fee: Beginning in calendar-year 2011, an annual fee was imposed on pharmaceutical manufacturers and importers that sell branded prescription drugs to specified government programs (e.g., Medicare Part D, Medicare Part B, Medicaid, Department of Veterans Affairs programs, Department of Defense programs and TRICARE).

The annual fee is allocated to companies based on their previous calendar-year market share using sales data that the government agencies that purchase the pharmaceuticals will provide to the Treasury Department. Although we participate in governmental programs that subject us to this fee, our sales volume in such programs is less than $10 million, with the first $5 million of sales being exempt from the fee. This fee has not had a material impact and is not expected to have a material impact on our results of operations.

Physician Payments Sunshine Act: The PPACA also includes provisions known as the Physician Payments Sunshine Act, or Sunshine Act, which require manufacturers of pharmaceuticals and medical devices covered under Medicare and Medicaid to record any transfers of value to physicians and teaching hospitals and to report this data to the Centers for Medicare and Medicaid Services, or CMS, for aggregation and subsequent public disclosure. Under the Sunshine Act, beginning August 1, 2013, we have collected data regarding reportable transfers of value and have reported such data to CMS. Failure to report appropriate data may result in civil or criminal fines and/or penalties. In addition to the Federal Sunshine Act, similar reporting requirements have also been enacted on the state level requiring transparency of interactions with health care professionals.

Medicaid Rebate Rate: We currently provide rebates for products sold to Medicaid beneficiaries.

Product Serialization:In November of 2013, the FDA passed the Drug Supply Chain Security Act (DSCSA). The DSCSA was created to strengthen the security of the drug distribution supply chain by adding controls such as a national pharmaceutical track and trace system and establishing national standards for licensing of prescription drug wholesale distributors and third-party logistics providers. DSCSA requires trading partners, including manufacturers, repackagers, wholesale distributors and dispensers to provide transaction information to subsequent purchasers for certain prescription drugs. We have taken necessary steps to implement this program and are in compliance with all requirements by the November 2018 deadline.

21stCentury Cures Act:The 21st Century Cures Act (Cures Act), signed into law on December 13, 2016, is designed to help accelerate medical product development and bring new innovations and advances to patients who need them faster and more efficiently. The law builds on FDA's ongoing work to incorporate the perspectives of patients into the development of drugs, biological products, and devices in FDA's decision-making process. Cures enhances FDA's ability to modernize clinical trial designs and clinical outcome assessments, which will speed the development and review of novel medical products, including medical countermeasures.

Specifically, the Cures Act enables us to work with FDA in the development of new biomarkers, clinical outcome assessments, surrogate endpoints, and patient reported outcomes. It allows for the use of data summaries rather than full clinical trials for approval and the use of real world evidence to support approval of new indications of approved medical products, or to help satisfy post-approval study requirements for marketed products.

Post Approval Activities

Once a drug is on the U.S. market (following FDA approval of the NDA), the FDA continues to address drug production, distribution, and use. FDA activities are based on ensuring drug safety and effectiveness, and address product integrity, labeling, reporting of research and adverse events, surveillance, drug studies, risk management, information dissemination, off-label use, physician advertising and direct-to-consumer advertising.

If we amend the NDA for an FDA approved product, such as adding safety or efficacy labeling claims, promoting those new claims, making certain manufacturing changes or product enhancements, we will need FDA review and approval before the change can be implemented. While physicians may use products for indications that have not been approved by the FDA, we may not label or promote the product for an indication that has not been approved.

Securing FDA approval for new indications, product enhancements, and manufacturing and labeling changes may require us to conduct additional clinical trials under FDA's IND regulations. Even if such studies are conducted, they are still subject to the same requirements and timelines as an original NDA.

The FDA continuously gathers information about possible adverse reactions to the products it has approved for use. The FDA requires all manufacturers to report adverse events. It also provides a procedure for consumers and physicians to voluntarily report their concerns about drugs. The agency collects those reports through MedWatch and uses its FDA Adverse Event Reporting System (FAERS) to store and analyze them. Because some events may occur after the use of a drug for reasons unrelated to the product, the FDA reviews the events to assess which ones may indicate a problem with that particular drug. They then use information gleaned from the surveillance data to determine a course of action. They might recommend a change in drug labeling to alert users to a potential problem, or, perhaps, to require the manufacturer to study the observed association between the drug and the adverse event.

In addition to FDA restrictions on marketing of pharmaceutical products, several other types of state and federal laws have been applied to restrict certain marketing practices in the pharmaceutical industry in recent years. These laws include anti-kickback statutes and false claims statutes. The federal health care program anti-kickback statute prohibits, among other things, knowingly and willfully offering, paying, soliciting or receiving remuneration to induce or in return for purchasing, leasing, ordering or arranging for the purchase, lease or order of any health care item or service reimbursable under Medicare, Medicaid or other federally financed health care programs. This statute has been interpreted to apply to arrangements between pharmaceutical manufacturers on the one hand and prescribers, purchasers and formulary managers on the other. Violations of the anti-kickback statute are punishable

by imprisonment, criminal fines, civil monetary penalties and exclusion from participation in federal health care programs.

Federal False Claims Act

The Federal false claims laws prohibit any person from knowingly presenting, or causing to be presented, a false claim for payment to the federal government, or knowingly making, or causing to be made, a false statement to have a false claim paid.

A number of pharmaceutical and other health care companies have been prosecuted under these laws for allegedly inflating drug prices they report to pricing services, which in turn were used by the government to set Medicare and Medicaid reimbursement rates, and for allegedly providing free product to customers with the expectation that the customers would bill federal programs for the product.

ICH – International Committee on Harmonization

Outside of the U.S., our ability to market our products will depend on receiving marketing authorizations from the appropriate regulatory authorities. The International Committee on Harmonization (ICH) provides a set of standards that most Regulatory Authorities adhere to (e.g. U.S., Europe, and Japan) allowing greater harmonization in the interpretation and application of technical guidelines and requirements for pharmaceutical product registration, thereby reducing or obviating duplication of testing carried out during the research and development of new human medicines. Regulatory harmonization offers many direct benefits to both regulatory authorities and the pharmaceutical industry with beneficial impact for the protection of public health.

ENVIRONMENTAL MATTERS

We are subject to federal, state and local environmental laws and regulations and we believe that our operations comply with such regulations. We anticipate that the effects of compliance with federal, state and local laws and regulations relating to the discharge of materials into the environment will not have any material effect on our capital expenditures, earnings or competitive position.

SEASONALITY

There are no significant seasonal aspects to our business.

BACKLOG

Due to the relatively short lead-time required to fill orders for our products, backlog of orders is not considered material to our business.

EMPLOYEES

As of December 31, 2019, we had 94 employees. We believe that our future will depend in part on our continued ability to attract, hire, and retain qualified personnel, including hospital and field sales personnel in particular.

Item 1A. Risk Factors.

The risk factors described below and throughout this report should be carefully considered and could materially affect our business. There are also risks that are not presently known or not presently material, as well as the other information set forth in this report that could materially affect our business. In addition, in our periodic filings with the SEC, press releases and other statements, we discuss estimates and projections regarding our future performance and business outlook. By their nature, such 'forward-looking statements' involve known and unknown risks, uncertainties and other factors that in some cases are out of our control. For a further discussion of forward-looking statements, please refer to the section entitled 'Special Note Regarding Forward-Looking Statements.' These factors could cause our actual results to differ materially from our historical results or our present expectations and projections. These risk factors and uncertainties include, but are not limited to the following:

RISKS RELATED TO OUR BUSINESS

Our business could be adversely affected by natural disasters, public health epidemics, and other events beyond our control.

Our business could be adversely impacted by the recent coronavirus ('COVID-19') outbreak which has affected more than 100 countries and has significantly disrupted the day-to-day activities of both individuals and businesses. We rely on individuals and third-party organizations around the world to supply components, manufacture and distribute our products and execute our clinical trials. We may experience revenue loss, supply interruptions, time delays and incur unplanned expenses as a result of the impact of the ongoing COVID-19 pandemic.

An adverse development regarding our products could have a material and adverse impact on our future revenues and profitability.

A number of factors may impact the effectiveness of our marketing and sales activities and the demand for our products, including:

Changes in intellectual property protection available for our products or competing treatments;

Any unfavorable publicity concerning us, our products, or the markets for these products such as information concerning product contamination or other safety issues in any of our product markets, whether or not directly involving our products;

Perception by physicians and other members of the healthcare community of the safety or efficacy of our products or competing products;

Regulatory developments related to our marketing and promotional practices or the manufacture or continued use of our products;

The prices of our products relative to other drugs or competing treatments;

The impact of current or additional generic competitors;

The availability and level of third-party reimbursement for sales of our products; e

The continued availability of adequate supplies of our products to meet demand.

If demand for our products weaken, our revenues and profitability will likely decline. Known adverse effects of our marketed products are documented in product labeling, including the product package inserts, medical information disclosed to medical professionals and all marketing-related materials. At this time, no unforeseen or serious adverse effects outside of those specified in current product labeling have been directly attributed to our approved products.

We currently market and sell six products: Acetadote, Caldolor, Kristalose, Vaprisol, Omeclamox-Pak, and Vibativ with RediTrex being marketed in early 2020. A product contamination or other safety or regulatory issues,

such as a failure to meet certain FDA reporting requirements involving our products could negatively impact us and possibly lead to a product recall. In addition, changes impacting any of our products in areas such as competition, lack of market acceptance or demand, government regulation, intellectual property, reimbursement and manufacturing could have an adverse impact on our future revenues and profitability.

The FDA has requested prescribers and manufacturers of prescription combination products that contain acetaminophen to limit the amount of acetaminophen to no more than 325 milligrams (mg) in each tablet or capsule. The FDA requested this action to protect consumers from the risk of severe liver damage which can result from excess acetaminophen. This category of prescription drugs combines acetaminophen with another ingredient intended to treat pain (most often an opioid), and these products are commonly prescribed to consumers for pain, such as pain from acute injuries, post-operative pain, or pain following dental procedures.

The FDA also requires manufacturers to appropriately label all prescription combination acetaminophen products to warn of the potential risk for severe liver injury. The actions the FDA is taking for prescription acetaminophen combination products do not affect over-the-counter acetaminophen products. The FDA's regulation of acetaminophen in prescription combination products and over-the-counter products may reduce the number of acetaminophen overdoses which could result in a lower demand for Acetadote. If the demand for Acetadote decreases, it could have an adverse impact on our future revenues and profitability.

The commercial success of Caldolor is dependent on many third-parties, including physicians, pharmacists, hospital pharmacy and therapeutics committees, or P&T committees, suppliers and distributors, all of whom we have little or no control over. We expect Caldolor to continue to be administered primarily to hospital and surgery center patients who are unable to receive oral therapies for the treatment of pain or fever. Before we can distribute Caldolor to any new hospital customers, Caldolor must be approved for addition to the hospitals' formulary lists by their P&T committees. A hospital's P&T committee generally governs all matters pertaining to the use of medications within the institution, including review of medication formulary data and recommendations of drugs to the medical staff. We cannot guarantee that we will be successful in getting the approvals we need from enough P&T committees to be able to optimize hospital sales of Caldolor. Even if we obtain hospital approval for Caldolor, we must still convince individual hospital physicians to prescribe Caldolor repeatedly. The commercial success of Caldolor also depends on our ability to coordinate supply, distribution, marketing, sales and education efforts. As with our other products, if Caldolor is not accepted in the marketplace, it could have an adverse impact on our future revenues and profitability.

If any manufacturer or partner we rely upon fails to supply our products in the amounts we require on a timely basis, or fails to comply with stringent regulations applicable to pharmaceutical drug manufacturers, we may be unable to meet demand for our products and may lose potential revenues.

We do not manufacture any of our products, and we do not currently plan to develop any capacity to do so. Our dependence upon third parties for the manufacture of our products could adversely affect our profit margins or our ability to develop and deliver products on a timely and competitive basis. If for any reason we are unable to obtain or retain third-party manufacturers on commercially acceptable terms, we may not be able to sell our products as planned. Furthermore, if we encounter delays or difficulties with contract manufacturers in producing our products, the distribution, marketing and subsequent sales of these products could be adversely affected.

Acetadote: Acetadote we have agreements with two manufacturers, and one manufacturer provided commercial supplies of the product during 2019. If the manufacturer of Acetadote is unable to produce marketable inventory in sufficient quantities, in the agreed upon time period, we could suffer an inability to meet demand for our product.

Caldolor:We have agreements with multiple manufacturers for the supply of Caldolor and during 2019 we obtained commercial supplies from three of these manufacturers for our international and domestic Caldolor requirements. If the manufacturers of Caldolor are unable to produce marketable inventory in sufficient quantities, in the agreed upon time period, we could suffer an inability to meet demand for our product.

Kristalose: The active pharmaceutical ingredient for Kristalose is manufactured at a single facility by an international supplier. We also have manufacturing relationships with two packagers who provided finished supplies of the product for commercial and sampling purposes during 2019. If these facilities are damaged or destroyed, or if

local conditions result in a work stoppage, we could suffer an inability to meet demand for our product. Kristalose is manufactured through a complex process. It would be particularly difficult to find a new manufacturer of Kristalose active pharmaceutical ingredient on an expedited basis. As a result of these factors, our ability to manufacture Kristalose may be substantially impaired if the manufacturer is unable or unwilling to supply sufficient quantities of the product.

Omeclamox-Pak: Prior to our asset purchase agreement with GEL that closed in December 2018, GEL managed the packaging and supply of Omeclamox-Pak commercial and sample units. Following our acquisition of the remaining rights to the brand in late 2018, we assumed responsibility for the packaging and supply of the product. During 2019 we entered into a new packaging arrangement for this product. If we are unable to obtain marketable inventory in the future, we could suffer an inability to meet demand for our product.

Vaprisol: As part of the acquisition of Vaprisol, we purchased an existing supply of raw material inventory. In addition, as part of this transaction, we were assigned a commercial supply agreement with the historical Vaprisol manufacturer. In 2018, the manufacturer informed us that they would no longer be able to provide the product following the manufacturing of one final batch which is expected to provide us with a multi-year supply. Therefore, we are evaluating alternatives for a new manufacturer to provide us with long term supplies of the product. If we are unable to produce additional marketable inventory in sufficient quantities of Vaprisol, we could suffer an inability to meet demand for our product.

Vibativ: Through our acquisition of Vibativ, we acquired a multi-year supply of raw material, work in process and finished goods inventory. As a result of the agreement, we are now responsible for the future manufacture of the product and completed the transfer of the product's manufacturing activities to a new supplier in 2019. If we are unable to obtain marketable inventory in the future, we could suffer an inability to meet demand for our product.

RediTrex: Under our agreement with Nordic, they will be responsible for providing us the packaged and labeled commercial supply of the RediTrex product. If we are unable to obtain marketable inventory in the future, we could suffer an inability to meet demand for our product.

In addition, all manufacturers of our products and product candidates must comply with current good manufacturing practices, ('GMPs'), enforced by the FDA through its facilities inspection program. These requirements include quality control, quality assurance and the maintenance of records and documentation. Manufacturers of our products may be unable to comply with GMP requirements and with other FDA, state and foreign regulatory requirements.

We have no control over our manufacturers' compliance with these regulations and standards. If our third-party manufacturers do not comply with these requirements, we could be subject to:

Fines and civil penalties;

Suspension of production or distribution;

Suspension or delay in product approval;

Product seizure or recall; e

Withdrawal of product approval.

We are dependent on a variety of other third parties. If these third parties fail to perform as we expect, our operations could be disrupted and our financial results could suffer.

We have a relatively small internal infrastructure. We rely on a variety of third parties, in addition to our manufacturers, to help us operate our business. Other third parties on which we rely include:

Cardinal Health Specialty Pharmaceutical Services, a logistics and fulfillment company and business unit of Cardinal, which bills for, collects, warehouses and ships our marketed products; e

Vanderbilt University, WinHealth and the Tennessee Technology Development Corporation, co-owners with us of CET, and the universities that collaborate with us in connection with CET's research and development programs.

If these third parties do not continue to provide services to us, or collaborate with us, we might not be able to obtain others who can serve these functions. This could disrupt our business operations, increase our operating expenses or otherwise adversely affect our operating results.

Competitive pressures could reduce our revenues and profits.

The pharmaceutical industry is intensely competitive. Our strategy is to target differentiated products in specialized markets. However, this strategy does not relieve us from competitive pressures and can entail distinct competitive risks. Certain of our competitors do not aggressively promote their products in our markets. An increase in promotional activity in our markets could result in large shifts in market share, adversely impacting us.

Our competitors may sell or develop drugs that are more effective and useful or less costly than ours, and they may be more successful in manufacturing and marketing their products. Many of our competitors have significantly greater financial and marketing resources than we do. Additional competitors may enter our markets.

The pharmaceutical industry is characterized by constant and significant investment in new product development, which can result in rapid technological change. The introduction of new products could substantially reduce our market share or render our products obsolete. The selling prices of pharmaceutical products tend to decline as competition increases, through new product introduction or otherwise, which could reduce our revenues and profitability.

If generic products that compete with any of our branded pharmaceutical products are approved and sold, sales of our products will be adversely affected.

Generic equivalents for branded pharmaceutical products are typically sold at lower costs than the branded products. The regulatory approval process in the United States exempts generic products from costly and time-consuming clinical trials to demonstrate their safety and efficacy and rely instead on the safety and efficacy of prior products, manufacturers of generic products can invest far less in research and development. After the introduction of a competing generic product, a significant percentage of the prescriptions previously written for the branded product are often written for the generic version. In addition, legislation enacted in most U.S. states allows or, in some instances mandates, that a pharmacist dispense an available generic equivalent when filling a prescription for a branded product, in the absence of specific instructions from the prescribing physician. Governmental and private healthcare payors also emphasize substitution of branded pharmaceuticals with less expensive generic equivalents. Pursuant to the provisions of the Hatch-Waxman Act, manufacturers of branded products often bring lawsuits to enforce their patent rights against generic products released prior to the expiration of branded products' patents, but it is possible for generic manufacturers to offer generic products while such litigation is pending. As a result, branded products typically experience a significant loss in revenues following the introduction of a competing

generic product, even if subject to an existing patent. Our branded pharmaceutical products are or may become subject to competition from generic equivalents because there is no proprietary protection for some of the branded pharmaceutical products we sell, because our patent protection expires or because our patent protection is not sufficiently broad or enforceable. In addition, we may not be successful in our efforts to extend the proprietary protection afforded our branded products through the development and commercialization of proprietary product improvements. Competition from generic equivalents could result in a decrease in revenues of our branded pharmaceuticals or result in a material impairment of our intangible assets or the acceleration of amortization on our non-impaired intangible assets and may have a material adverse impact on our revenues, financial condition, results of operations and cash flows.

Any attempt by us to expand the potential market for any of our products is subject to limitations.

Expansion of the market for our products may be subject to certain limitations. In the past, these limitations have included FDA required Phase IV commitments. We may also experience delays associated with future required Phase IV clinical studies potentially resulting from, among other factors, difficulty enrolling patients. Such delays could impact our ability to explore opportunities for label expansion and limit our ability to bring our products to new patient populations.

In addition, we have only obtained regulatory approval to market our products in the United States. Not all foreign jurisdictions may represent attractive opportunities for our products due to pricing, competitive, regulatory or other factors. In certain foreign jurisdictions, we have licensed the right to market some of our products to third parties. These third parties are responsible for seeking regulatory approval for the products in their respective jurisdictions. We have no control over these third parties and cannot be sure that marketing approval for our products will be obtained outside the United States.

Our future growth depends on our ability to identify and acquire rights to products. If we do not successfully identify and acquire rights to products, our growth opportunities may be limited.

We acquired rights to our products and our product candidates. Our business strategy is to continue to acquire rights to FDA-approved products as well as pharmaceutical product candidates in the late stages of development. We do not plan to conduct basic research or preclinical product development, except to the extent of our investment in CET. As compared to large multi-national pharmaceutical companies, we have limited resources to acquire third-party products, businesses and technologies and integrate them into our current infrastructure. Many acquisition opportunities involve competition among several potential purchasers including large multi-national pharmaceutical companies and other competitors that have access to greater financial resources than we do. With future acquisitions, we may face financial and operational risks and uncertainties. We may not be able to engage in future product acquisitions, and those we do complete may not be beneficial to us in the long term.

Furthermore, other products in development may encounter unforeseen issues during their clinical trials. Any unforeseen issues or lack of FDA approval will negatively affect marketing and development plans for those products.

Our future growth depends on our ability to successfully integrate acquired product brands into our operations. If we do not successfully integrate acquired product brands into our operations, our growth opportunities may be limited.

We added five marketed products to our portfolio of brands, roughly one brand per year, beginning in late 2013 through late 2018. If we are unable to continue to optimize our sales of our brands or we are unable to successfully integrate the marketing, sale and distribution of any other potential products into our current infrastructure or if they require significantly greater resources than originally anticipated, we may face financial and operational risks and uncertainties. If we are unable to successfully integrate any acquired brands, both current and future, these product acquisitions may not be beneficial to us in the long term.

Our Hepatoren, Boxaban, Vasculan, Portaban, and RediTrex product candidates have not been approved for sale and may never be successfully commercialized.

We anticipate that a portion of our future revenue growth will come from sales of our Hepatoren, Boxaban, Vasculan, Portaban, and RediTrex product candidates. Hepatoren (intravenous ifetroban) is used to treat hepatorenal syndrome ('HRS'), Boxaban (oral ifetroban) is used to treat aspirin exacerbated respiratory disease ('AERD'), Vasculan (oral ifetroban) is for the treatment of systemic sclerosis ('SSc'), Portaban (injection and oral ifetroban) is for the treatment of portal hypertension associated with liver disease, and methotrexate (injection) is used to treat active rheumatoid, juvenile idiopathic and severe psoriatic arthritis as well as severe disabling psoriasis. However, none of these products have been approved by the FDA for marketing, and these product candidates are still subject to risks associated with their development.

The FDA has cleared our IND's for the ifetroban product candidates as we evaluate them as treatments for these conditions. Delays in the enrollment and completion of the clinical studies could significantly delay commercial launch and affect our product development costs. Moreover, results from the clinical studies may not be favorable.

Even if they are eventually developed and approved by the FDA, they may never gain significant acceptance in the marketplace and therefore never generate substantial revenue or profits for us. Physicians may determine that existing drugs are adequate to address patients' needs. The extent to which these product candidates will be reimbursed by the U.S. government or third-party payors is also currently unknown.

As a result of the foregoing and other factors, we do not know the extent to which our product candidates will contribute to our future growth.

If we are unable to maintain, train and build an effective sales and marketing infrastructure, we will not be able to commercialize and grow our products and product candidates successfully.

As we grow, we may not be able to secure sales personnel or organizations that are adequate in number or expertise to successfully market and sell our products. This risk would be accentuated if we acquire products in areas outside of our current focus areas since our sales forces specialize in our existing areas. If we are unable to expand our sales and marketing capability, train our sales force effectively or provide any other capabilities necessary to commercialize our products and product candidates, we will need to contract with third parties to market and sell our products. We must train our employees on proper regulatory compliance, including, but not limited to, 'fair balance' promotion of our products and anti-kickback laws. If we are unable to establish and maintain compliant and adequate sales and marketing capabilities, we may not be able to increase our product revenue, may generate increased expenses and may experience regulatory compliance issues.

If governmental or third-party payors do not provide adequate reimbursement for our products, our revenue and prospects for profitability may be limited.

Our financial success depends, in part, on the availability of adequate reimbursement from third-party healthcare payors. Such third-party payors include governmental health programs such as Medicare and Medicaid, managed care providers and private health insurers. Third-party payors are increasingly challenging the pricing of medical products and services, while governments continue to propose and pass legislation designed to reduce the cost of healthcare. Adoption of such legislation could further limit reimbursement for pharmaceuticals.

In March 2010, the U.S. government passed into law the Patient Protection and Affordable Care Act, ('PPACA') along with the Health Care and Education Reconciliation Act of 2010, ('HCERA'), which modified the revenue provisions of the PPACA. The legislation calls for an increase in certain Medicare drug rebates paid by pharmaceutical manufacturers and an industry fee imposed on pharmaceutical manufacturers according to the individual manufacturer's relative percentage of total industry sales to specified government programs. At this time no assurances can be given that these measures, or any other measures included in the Healthcare Reform Act, will not have an adverse effect on our revenues in the future. Future cost control initiatives, legislation and regulations could decrease the price that we receive for any products, which would limit our revenue and profitability.

Since its inception, other legislative changes have been proposed and adopted. These changes included aggregate reductions of Medicare payments to providers of up to two percent per fiscal year. Additionally, in January 2013, the American Taxpayer Relief Act of 2012, was signed into law which, among other things, reduced Medicare payments to several providers, and increased the statute of limitations period for the government to recover overpayments to providers from three to five years. Further, while the healthcare reform agenda and policies of the current administration are not fully known, it is possible that additional regulatory changes may take place. This includes a repeal of all or portions of the PPACA, and Congress could be asked to replace the current legislation of the PPACA. There is uncertainty with respect to the timing and impact of any changes. These changes could have an impact on coverage and reimbursement for healthcare products and services covered by plans that were authorized by the PPACA. At this time, we cannot predict the ultimate content, timing or effect of any healthcare reform legislation or the impact of potential legislation on us.

Also, reimbursement practices of third-party payors might preclude us from achieving market acceptance for our products or maintaining price levels sufficient to realize an appropriate return on our investment in product acquisition and development. If we cannot obtain adequate reimbursement levels, our business, financial condition and results of operations would be materially and adversely affected.

Our employees have been trained to submit accurate and correct pricing information to payors. If, despite the training, our employees provide incorrect or fraudulent information, then we will be subject to various administrative and judicial investigations and litigation.

'Formulary' practices of third-party payors could adversely affect our competitive position.

Many managed healthcare organizations are now controlling the pharmaceutical products included on their formulary lists. Having products listed on these formulary lists creates competition among pharmaceutical companies which, in turn, has created a trend of downward pricing pressure in our industry. In addition, many managed care organizations are pursuing various ways to reduce pharmaceutical costs and are considering formulary contracts primarily with those pharmaceutical companies that can offer a full line of products for a given therapy sector or disease state. Our products might not be included on the formulary lists of managed care organizations, and downward pricing pressure in our industry generally could negatively impact our operations.

Continued consolidation of distributor networks in the pharmaceutical industry as well as increases in retailer concentration may limit our ability to profitably sell our products.

We sell most of our products to large pharmaceutical wholesalers, who in turn sell to hospitals, surgery centers and retail pharmacies. The distribution network for pharmaceutical products has become increasingly consolidated in recent years. Further consolidation or financial difficulties could also cause our customers to reduce the amounts of our products that they purchase, adversely impacting our business, financial condition and results of operations.

Our CET joint initiative may not result in our gaining access to commercially viable products.

Our CET joint initiative with Vanderbilt University, WinHealth and Tennessee Technology Development Corporation is designed to help us investigate, in a cost-effective manner, early-stage products and technologies. However, we may never gain access to commercially viable products from CET for a variety of reasons, including:

CET investigates early-stage products, which have risk of failure prior to FDA approval and commercialization;

In some programs, we do not have pre-set rights to product candidates developed by CET. We would need to agree with CET and its collaborators on the terms of any product licensed or acquired by us;

We rely principally on government grants to fund CET's research and development programs. If these grants were no longer available, we or our co-owners might be unable or unwilling to fund CET operations at current levels or at all;

We may become involved in disputes with our co-owners regarding CET policy or operations, such as how best to deploy CET assets or which product opportunities to pursue. Disagreement could disrupt or halt product development; e

CET may disagree with one of the various universities with which CET is collaborating on research. A disagreement could disrupt or halt product development.

We depend on our key personnel, the loss of whom would adversely affect our operations. If we fail to attract and retain the talent required for our business, our business will be materially harmed.

We are a relatively small company, and we depend to a great extent on principal members of our management, scientific staff, and sales representatives and managers. If we lose the services of any key personnel, in particular, A.J. Kazimi, our Chief Executive Officer, or other members of senior management it could have a material adverse effect on our business prospects. Mr. Kazimi, plays a key role in several operational and strategic decisions such that any loss of his services due to death or disability would adversely impact our day-to-day operations. We have a life insurance policy covering the life of Mr. Kazimi. We have entered into agreements with each of our employees that contain restrictive covenants relating to non-competition and non-solicitation of our customers and suppliers for one year after termination of employment. Nevertheless, each of our officers and key employees may terminate his or her employment at any time without notice and without cause or good reason, and so as a practical matter these agreements do not guarantee the continued service of these employees. Our success depends on our ability to attract and retain highly qualified scientific, technical, sales and managerial personnel and research partners. Competition among pharmaceutical companies for qualified employees is intense, and we may not be able to retain existing personnel or attract and retain qualified staff in the future. If we experience difficulties in hiring and retaining personnel in key positions, we could suffer from delays in product development, loss of customers and sales and diversion of management resources, which could adversely affect operating results.

The size of our organization and our potential growth may lead to difficulties in managing operations.

As of December 31, 2019, we had 94 employees. We may need to continue to expand our managerial, operational, financial and other resources in order to increase our marketing efforts with regard to our currently marketed products, continue our business development and product development activities and commercialize our product candidates. We have experienced, and may continue to experience, growth and increased expenses in the scope of our operations in connection with the continued marketing and development of our products. Our financial performance will depend, in part, on our ability to manage any such growth and expenses of the current organization effectively.

We face potential product liability exposure, and if successful claims are brought against us, we may incur substantial liability for a product or product candidate and may have to limit its commercialization.

We face an inherent risk of product liability lawsuits related to the testing of our product candidates and the commercial sale of our products. An individual may bring a liability claim against us if one of our product candidates or products causes, or appears to have caused, an injury. If we cannot successfully defend ourselves against the product liability claim, we may incur substantial liabilities. Liability claims may result in:

Decreased demand for our products;

Injury to our reputation;

Withdrawal of clinical trial participants;

Significant litigation costs;

Substantial monetary awards to or costly settlement with patients;

Product recalls;

Loss of revenue; e

The inability to commercialize our product candidates.

We are highly dependent upon medical and patient perceptions of us and the safety and quality of our products. We could be adversely affected if we or our products are subject to negative publicity. We could also be adversely affected if any of our products or any similar products sold by other companies prove to be, or are asserted to be,

harmful to patients. Also, because of our dependence upon medical and patient perceptions, any adverse publicity associated with illness or other adverse effects resulting from the use or misuse of our products or any similar products sold by other companies could have a material adverse impact on our results of operations.

We have product liability insurance that covers our clinical trials, the marketing and sale of our products up to a $10 million annual aggregate limit, subject to specified deductibles. Our current or future insurance coverage may prove insufficient to cover any liability claims brought against us.

Because of the increasing costs of insurance coverage, we may not be able to maintain insurance coverage at a reasonable cost or obtain insurance coverage that will be adequate to satisfy any liability that may arise.

Regulatory approval for any approved product is limited by the FDA to those specific indications and conditions for which clinical safety and efficacy have been demonstrated.

Any regulatory approval is limited to those specific diseases and indications for which a product is deemed to be safe and effective by the FDA. In addition to the FDA approval required for new formulations, any new indication for an approved product also requires FDA approval. If we are not able to obtain FDA approval for any desired future indications for our products, our ability to effectively market and sell our products may be reduced and our business may be adversely affected.

While physicians may choose to prescribe drugs for uses that are not described in the product's labeling and for uses that differ from those tested in clinical studies and approved by the regulatory authorities, our ability to promote the products is limited to those indications that are specifically approved by the FDA. These 'off-label' uses are common across medical specialties and may constitute an appropriate treatment for some patients in varied circumstances. Regulatory authorities in the U.S. generally do not regulate the behavior of physicians in their choice of treatments. Regulatory authorities do, however, restrict communications by pharmaceutical companies on the subject of off-label use. If our promotional activities fail to comply with these regulations or guidelines, we may be subject to warnings from, or enforcement action by, these authorities. In addition, our failure to follow FDA rules and guidelines relating to promotion and advertising may cause the FDA to suspend or withdraw an approved product from the market, require a recall or payment of fines, or could result in disgorgement of money, operating restrictions, injunctions or criminal prosecution, any of which could harm our business.

Our business and operations would suffer in the event of system failures, security breaches, including any cybersecurity incidents, adverse events or other disruptions within our information technology infrastructure at our corporate headquarters.

Despite the implementation of security measures, our internal computer systems, including those at our corporate headquarters, are vulnerable to damage from cyber-attacks, computer viruses, unauthorized access, natural disasters, terrorism, war and telecommunication and electrical failures. In the ordinary course of our business, we store sensitive data, including intellectual property, our proprietary business information and that of our customers. We also maintain personally identifiable information of our employees in our data centers and on our networks. The secure processing and maintenance of this information is critical to our operations. In the event that our corporate headquarters and/or our computer systems are disabled or materially damaged, it would have a substantial and material negative effect on our operations. Furthermore, any system failure, accident or security breach that causes interruptions in our operations could result in a material disruption of our drug development programs. While we continue to invest in data protection and information technology, our information technology and infrastructure may be vulnerable to attacks by hackers or breached due to employee error, malfeasance or other disruptions. Any such breach could compromise our networks and the information stored there could be accessed, publicly disclosed, lost or stolen. To the extent that any disruption or security breach results in a loss or damage to our data or applications, or inappropriate disclosure of confidential or proprietary information, we may incur liability and the further development of our products or product candidates may be delayed.

We may develop internationally and license our products globally; therefore, we may have an increased exposure to foreign regulatory requirements and fluctuations in foreign currency exchange rates.

While we currently have only obtained regulatory approval to market our products in the United States, in the future we may seek global opportunities for our products and to develop product candidates internationally in the future. Such opportunities and development will inherently subject us to a number of risks and uncertainties, including:

longer payment cycles and difficulties in enforcing agreements and collecting receivables through certain foreign legal systems;

political and economic instability or sanctions in areas in which we operate;

potentially adverse tax consequences, tariffs, customs charges, bureaucratic requirements and other trade barriers;

regulations related to customs and import/export matters (including sanctions);

tax issues, such as tax law changes and variations in tax laws;

challenges in collecting accounts receivable from customers in the jurisdictions in which we operate;

complying with laws, rules and regulations relating to the manufacturing, marketing, distribution and sale of pharmaceutical products in the jurisdictions in which we do or will operate;

operating under regulations in jurisdictions related to obtaining eligibility for government or private payor reimbursement for our products at the wholesale/retail level;

competition from local, regional and international competitors;

difficulties and costs of staffing and managing foreign operations, including cultural and language differences and additional employment regulations, union workforce negotiations and potential disputes in the jurisdictions in which we operate;

difficulties associated with compliance with a variety of laws and regulations governing international trade, including the Foreign Corrupt Practices Act;

difficulties protecting or procuring intellectual property rights; e

fluctuations in foreign currency exchange rates.

Any of these factors may, individually or as a group, have a material adverse effect on our business and results of operations. These or other similar risks could adversely affect our revenue and profitability. As we develop internationally, our exposure to these factors will increase.

Even if a drug candidate that we develop receives regulatory approval, we may decide not to commercialize it if we determine that commercialization of that product would require more capital and time than we are willing to invest.

Even if any of our drug candidates receives regulatory approval, it could be subject to post-regulatory surveillance, and may have to be withdrawn from the market or subject to restrictions if previously unknown problems occur. Regulatory agencies may also require additional clinical trials or testing, and the drug product may be recalled or may be subject to reformulation, additional studies, changes in labeling, warnings to the public and negative publicity. As a result, we may not continue to commercialize a product even though it has obtained regulatory approval. Further, we may decide not to continue to commercialize a product if the market does not accept the product because it is too expensive or because third parties, such as insurance companies or Medicare, have not approved it for substantial reimbursement. In addition, we may decide not to continue to commercialize a product if competitors develop and commercialize similar or superior products or have proprietary rights that preclude us from ultimately marketing our products.

Any approved drug product that we bring to the market may not gain market acceptance by physicians, patients, healthcare payors and others in the medical community.

Even if we are successful in gaining regulatory approval of any of our drug candidates or acquire rights to approved drug products, we may not generate significant product revenues and we may not become profitable if these drug products do not achieve an adequate level of acceptance. Physicians may not recommend our drug products until longer-term clinical data or other factors demonstrate the safety and efficacy of our drug products as compared to other alternative treatments. Even if the clinical safety and efficacy of our drug products is established, physicians may elect not to prescribe these drug products for a variety of reasons, including the reimbursement policies of government and other third-party payors and the effectiveness of our competitors in marketing their products.

Market acceptance of our drug products, if approved for commercial sale, will depend on a number of factors, including:

the willingness and ability of patients and the healthcare community to use our drug products;

the ability to manufacture our drug products in sufficient quantities with acceptable quality and to offer our drug products for sale at competitive prices;

the perception of patients and the healthcare community, including third-party payors, regarding the safety, efficacy and benefits of our drug products compared to those of competing products or therapies;

the label and promotional claims allowed by the FDA; e

the pricing and reimbursement of our drug products relative to existing treatments.

We may acquire businesses or assets, form joint ventures or make investments in other companies that may be unsuccessful, divert our management's attention and harm our operating results and prospects.

As part of our business strategy, we may pursue additional acquisitions of what we believe to be complementary businesses or assets or seek to enter into joint ventures. We also may pursue strategic alliances in an effort to leverage our existing infrastructure and industry experience to expand our product offerings or distribution, or make investments in other companies. The success of our acquisitions, joint ventures, strategic alliances and investments will depend on our ability to identify, negotiate, complete and, in the case of acquisitions, integrate those transactions and, if necessary, obtain satisfactory debt or equity financing to fund those transactions. We may not realize the anticipated benefits of any acquisition, joint venture, strategic alliance or investment. We may not be able to integrate acquisitions successfully into our existing business, maintain the key business relationships of businesses we acquire, or retain key personnel of an acquired business, and we could assume unknown or contingent liabilities or incur unanticipated expenses. Integration of acquired companies or businesses also may require management resources that otherwise would be available for ongoing development of our existing business. Any acquisitions or investments made by us also could result in significant write-offs or the incurrence of debt and contingent liabilities, any of which could harm our operating results. In addition, if we choose to issue shares of our stock as consideration for any acquisition, dilution to our shareholders could result.

The acquisitions we have made or make in the future may make us the subject of lawsuits from either an acquired company's shareholders, an acquired company's previous shareholders, or our current shareholders.

We may be the subject of lawsuits from either an acquired company's shareholders, an acquired company's previous shareholders, or our current shareholders. These lawsuits could result from the actions of the acquisition target prior to the date of the acquisition, from the acquisition transaction itself, or from actions after the acquisition. Defending potential lawsuits could cost us significant expense and distract management's attention from the operation of the business. Additionally, these lawsuits could result in the cancellation of, or the inability to renew, certain insurance coverage that would be necessary to protect our assets.

We may be required to modify our business practices, pay fines and significant expenses or experience other losses due to governmental investigations or other enforcement activities.

We may become subject to litigation or governmental investigations in the United States and foreign jurisdictions that may arise from the conduct of our business. Like many companies in our industry, we have from time to time received inquiries and other types of information requests from government authorities.

While the ultimate outcomes of investigations and legal proceedings are difficult to predict, adverse resolutions or settlements of those matters could result in, among other things:

significant damage awards, fines, penalties or other payments, and administrative remedies, such as exclusion and/or debarment from government programs, or other rulings that preclude us from operating our business in a certain manner;

changes and additional costs to our business operations to avoid risks associated with such litigation or investigations;

product recalls;

reputational damage and decreased demand for our products; e

expenditure of significant time and resources that would otherwise be available for operating our business.

RISKS RELATING TO GOVERNMENT REGULATION

We are subject to stringent government regulation. All of our products face regulatory challenges.

Virtually all aspects of our business activities are regulated by government agencies. The manufacturing, processing, formulation, packaging, labeling, distribution, promotion and sampling, advertising of our products, and disposal of waste products arising from such activities are subject to governmental regulation. These activities are regulated by one or more of the FDA, the Federal Trade Commission, ('FTC'), the Consumer Product Safety Commission, the U.S. Department of Agriculture and the U.S. Environmental Protection Agency, ('EPA'), as well as by comparable agencies in foreign countries. These activities are also regulated by various agencies of the states and localities in which our products are sold. For more information, see 'Business-Government Regulation'.

Like all pharmaceutical manufacturers, we are subject to regulation by the FDA under the FDCA. All new drugs must be the subject of an FDA-approved new drug application, ('NDA'), before they may be marketed in the United States. The FDA has the authority to withdraw existing NDA approvals and to review the regulatory status of products marketed under the enforcement policy. The FDA may require an approved NDA for any drug product marketed under the enforcement policy if new information reveals questions about the drug's safety and effectiveness. All drugs must be manufactured in conformity with GMP, and drug products subject to an approved NDA must be manufactured, processed, packaged, held and labeled in accordance with information contained in the NDA. Since we rely on third parties to manufacture our products, GMP requirements directly affect our third party manufacturers and indirectly affect us. The manufacturing facilities of our third-party manufacturers are continually subject to inspection by such governmental agencies, and manufacturing operations could be interrupted or halted in any such facilities if such inspections prove unsatisfactory. Our third-party manufacturers are subject to periodic inspection by the FDA to assure such compliance.

Even after regulatory approval, certain developments may decrease demand for our products, including the following:

the re-review of products that are already marketed;

new scientific information and evolution of scientific theories;

the recall or loss of marketing approval of products that are already marketed;

changing government standards or public expectations regarding safety, efficacy or labeling changes; e

greater scrutiny in advertising and promotion.

In the past, clinical trials and post-marketing surveillance of certain marketed drugs of competitors within the industry have raised concerns that have led to recalls, withdrawals or adverse labeling of marketed products. If previously unknown side effects are discovered or if there is an increase in negative publicity regarding known side effects of any of our products, it could significantly reduce demand for the product or require us to take actions that could negatively affect sales, including removing the product from the market, restricting its distribution or applying for labeling changes.

In addition, certain health authorities, regulators and agencies have increased their focus on safety when assessing the balance of benefits and risks of drugs. Some health authorities appear to have become more cautious when making decisions about approvability of new products and are re-reviewing select products that are already marketed, adding further to the uncertainties in the regulatory processes. There is also greater regulatory scrutiny, especially in the U.S., on advertising, and promotion (in particular, direct-to-consumer advertising) and pricing of pharmaceutical products. Certain regulatory changes or decisions could make it more difficult for us to sell our products and could have a material adverse effect on our business, results of operations, financial condition and cash flows.

Manufacturers of drug products and their facilities are subject to continual review and periodic inspections by the FDA and other regulatory authorities for compliance with GMP and other applicable regulations. If we or a regulatory agency discovers previously unknown problems with a product, such as adverse events of unanticipated severity or frequency, or problems with a facility where the product is manufactured, a regulatory agency may impose restrictions on that product or the manufacturer, including withdrawal of the product from the market or suspension of manufacturing. If we, our partners or the manufacturing facilities for our products fail to comply with applicable regulatory requirements, a regulatory agency may take the following actions, among others:

issue warning letters or untitled letters;

impose civil or criminal penalties

suspend or withdraw regulatory approval;

suspend any ongoing clinical trials;

refuse to approve pending applications or supplements to applications submitted by us;

impose restrictions on operations, including costly new manufacturing requirements; o

seize or detain products or require us to initiate a product recall.

Any change in the FDA's enforcement policy could have a material adverse effect on our business, financial condition and results of operations. We cannot determine what effect changes in regulations or statutes or legal interpretation, when and if promulgated or enacted, may have on our business in the future. Such changes, or new legislation, could have a material adverse effect on our business, financial condition and results of operations.

Proposed legislation may permit re-importation of drugs from other countries into the U.S., including foreign countries where the drugs are sold at lower prices than in the U.S., which could materially and adversely affect our operating results and our overall financial condition.

In previous years, legislation has been introduced in Congress that, if enacted, would permit more widespread re-importation of drugs from foreign countries into the U.S., which may include re-importation from foreign countries where the drugs are sold at lower prices than in the U.S. Based on recent election results, there could be a renewed effort for legislation permitting the re-importation of prescription drugs as a means of lowering drug costs. Such legislation, or similar regulatory changes, if enacted, could decrease the price we receive for any approved products which, in turn, could materially and adversely affect our operating results and our overall financial condition.

We must comply with the Foreign Corrupt Practices Act.

We are required to comply with the United States Foreign Corrupt Practices Act, which prohibits U.S. companies from engaging in bribery or other prohibited payments to foreign officials for the purpose of obtaining or retaining business. Foreign companies, including some of our competitors, are not subject to these prohibitions. If our competitors engage in these practices, they may receive preferential treatment from officials or agencies in some countries, giving our competitors an advantage in securing business from government officials who might give them priority in obtaining new licenses, which would put us at a disadvantage. We have established formal policies or procedures for prohibiting or monitoring this conduct, but we cannot assure you that our employees or other agents will not engage in such conduct for which we might be held responsible. If our employees or other agents are found to have engaged in such practices, we could suffer severe penalties.

We must comply with the Physician Payment Sunshine Act.

We are required to comply with the United States Physician Payment Sunshine Act, which requires manufacturers of drugs, medical devices and biologicals that participate in U.S. federal healthcare programs to report certain payments and items of value given to physicians and teaching hospitals. Manufacturers are required to report this information annually to The Centers for Medicare & Medicaid Services (CMS). Cumberland has implemented a series of policies and procedures for every employee involved in the data collection process, and has systems in place to capture the data, which is verified by an outside firm that specializes in reporting the payments. Cumberland has also established a system to ensure that data was reported completely, in the correct format, and on time. Despite these policies, procedures and systems, we cannot assure you that we will collect and report all data accurately. If we fail to accurately report this information, we could suffer severe penalties.

If we fail to comply with our reporting and payment obligations under the Medicaid Drug Rebate program or other governmental pricing programs, we could be subject to additional reimbursement requirements, penalties, sanctions and fines, which could have a material adverse effect on our business, financial condition, results of operations and growth prospects.

We participate in and have certain price reporting obligations to the Medicaid Drug Rebate program and other governmental pricing programs, and we have obligations to report average sales price under the Medicare program.

Under the Medicaid Drug Rebate program, we are required to pay a rebate to each state Medicaid program for our covered outpatient drugs that are dispensed to Medicaid beneficiaries and paid for by a state Medicaid program as a condition of having federal funds being made available to the states for our drugs under Medicaid and Medicare Part B. Those rebates are based on pricing data reported by us on a monthly and quarterly basis to CMS, the federal agency that administers the Medicaid Drug Rebate program. These data include the average manufacturer price and, in the case of innovator products, the best price for each drug which, in general, represents the lowest price available from the manufacturer to any entity in the US in any pricing structure, calculated to include all sales and associated rebates, discounts and other price concessions.

The Healthcare Reform Act made significant changes to the Medicaid Drug Rebate program, such as expanding rebate liability from fee-for-service Medicaid utilization to include the utilization of Medicaid managed care organizations as well and changing the definition of average manufacturer price. The Healthcare Reform Act also increased the minimum Medicaid rebate; changed the calculation of the rebate for certain innovator products that qualify as line extensions of existing drugs; and capped the total rebate amount at 100% of the average manufacturer price. Finally, the Healthcare Reform Act requires pharmaceutical manufacturers of branded prescription drugs to pay a branded prescription drug fee to the federal government.

CMS issued final regulations to implement the changes to the Medicaid Drug Rebate program under the Healthcare Reform Act. These regulations became effective on April 1, 2016. The issuance of the final regulations and coverage expansion by various governmental agencies relating to the Medicaid Drug Rebate program has and will continue to increase our costs and the complexity of compliance, has been and will continue to be time-consuming to implement, and could have a material adverse effect on our results of operations, particularly if CMS challenges the approach we take in our implementation of the final regulations.

Federal law requires that any company that participates in the Medicaid Drug Rebate program also participate in the Public Health Service's 340B drug pricing program in order for federal funds to be available for the manufacturer's drugs under Medicaid and Medicare Part B. The 340B program requires participating manufacturers to agree to charge no more than the 340B 'ceiling price' for the manufacturer's covered outpatient drugs to a variety of community health clinics and other entities that receive health services grants from the Public Health Service, as well as hospitals that serve a disproportionate share of low-income patients. The Healthcare Reform Act expanded the list of covered entities to include certain free-standing cancer hospitals, critical access hospitals, rural referral centers and sole community hospitals. The 340B ceiling price is calculated using a statutory formula based on the average manufacturer price and rebate amount for the covered outpatient drug as calculated under the Medicaid Drug Rebate program. Changes to the definition of average manufacturer price and the Medicaid rebate amount under the Healthcare Reform Act and CMS's final regulations implementing those changes also could affect our 340B ceiling price calculations and negatively impact our results of operations.

The Healthcare Reform Act obligates the Secretary of the HHS to update the agreement that manufacturers must sign to participate in the 340B program to obligate a manufacturer to offer the 340B price to covered entities if the manufacturer makes the drug available to any other purchaser at any price and to report to the government the ceiling prices for its drugs. The Health Resources and Services Administration ('HRSA'), the federal agency that administers the 340B program, recently updated the agreement with participating manufacturers. The Healthcare Reform Act also obligates the Secretary of the HHS to create regulations and processes to improve the integrity of the 340B program. On January 5, 2017, HRSA issued a final regulation regarding the calculation of 340B ceiling price and the imposition of civil monetary penalties on manufacturers that knowingly and intentionally overcharge covered entities. The regulation became effective as of January 1, 2019. Implementation of this final rule and the issuance of any other final regulations and guidance could affect our obligations under the 340B program in ways we cannot anticipate. In addition, legislation may be introduced that, if passed, would further expand the 340B program to additional covered entities or would require participating manufacturers to agree to provide 340B discounted pricing on drugs used in the inpatient setting.

Federal law also requires that a company that participates in the Medicaid Drug Rebate program report average sales price information each quarter to CMS for certain categories of drugs that are paid under the Medicare Part B program. Manufacturers calculate the average sales price based on a statutorily defined formula as well as regulations and interpretations of the statute by CMS. CMS uses these submissions to determine payment rates for drugs under Medicare Part B. Statutory or regulatory changes or CMS guidance could affect the average sales price calculations for our products and the resulting Medicare payment rate, and could negatively impact our results of operations. Also, the Medicare Part B drug payment methodology is subject to change based on potential demonstration projects undertaken by CMS or potential legislation enacted by Congress.

Pricing and rebate calculations vary across products and programs, are complex, and are often subject to interpretation by us, governmental or regulatory agencies and the courts. In the case of our Medicaid pricing data, if we become aware that our reporting for a prior quarter was incorrect, or has changed as a result of recalculation of the pricing data, we are obligated to resubmit the corrected data for up to three years after those data originally were due. Such restatements and recalculations increase our costs for complying with the laws and regulations governing the Medicaid Drug Rebate program and could result in an overage or underage in our rebate liability for past quarters. Price recalculations also may affect the ceiling price at which we are required to offer our products under the 340B program.

We are liable for errors associated with our submission of pricing data. In addition to retroactive rebates and the potential for 340B program refunds, if we are found to have knowingly submitted any false price information to the government, we may be liable for civil monetary penalties. If we are found to have made a misrepresentation in the reporting of our average sales price, the Medicare statute provides for civil monetary penalties for each misrepresentation for each day in which the misrepresentation was applied. Our failure to submit the required price data on a timely basis could result in a civil monetary penalty per day for each day the information is late beyond the due date. Such failure also could be grounds for CMS to terminate our Medicaid drug rebate agreement, pursuant to which we participate in the Medicaid program. In the event that CMS terminates our rebate agreement, federal payments may not be available under Medicaid or Medicare Part B for our covered outpatient drugs.

CMS and the OIG have pursued manufacturers that were alleged to have failed to report these data to the government in a timely manner. Governmental agencies may also make changes in program interpretations, requirements or conditions of participation, some of which may have implications for amounts previously estimated or paid. We cannot assure you that our submissions will not be found by CMS to be incomplete or incorrect.

In order to be eligible to have our products paid for with federal funds under the Medicaid and Medicare Part B programs we are required to participate in the VA Federal Supply Schedule ('FSS') pricing program, established under Section 603 of the Veterans Health Care Act of 1992.

Failure to make necessary disclosures and/or to identify contract overcharges can result in allegations against us under the False Claims Act and other laws and regulations. Unexpected refunds to the government, and any response to government investigation or enforcement action, would be expensive and time-consuming, and could have a material adverse effect on our business, financial condition, results of operations and growth prospects.

RISKS RELATING TO INTELLECTUAL PROPERTY

Our strategy to secure and extend marketing exclusivity or patent rights may provide only limited or no protection from competition.

We seek to secure and extend marketing exclusivity for our products through a variety of means, including FDA exclusivity and patent rights. Additional barriers for competitors seeking to enter the market include the time and cost associated with the development, regulatory approval and manufacturing of a similar product formulation.

As discussed in Part I, Item 1, Business – Patents, Trademarks, and Other Intellectual Proprietary Rights,of this report on Form 10-K, we have several patents for formulations of Acetadote, and have previously engaged in litigation to enforce our patent rights.

We also have additional patent applications relating to Acetadote which are pending with the USPTO and may or may not be issued. We intend to continue to vigorously defend and protect our Acetadote product and related intellectual property rights. If we are unsuccessful in protecting our Acetadote intellectual property rights, our competitors may be able to introduce products into the marketplace that reduce the sales and market share of our Acetadote product which may require us to take measures such as reducing prices or increasing our marketing expense, any of which may result in a material adverse effect to our financial condition and results of operations.

While we consider patent protection when evaluating product acquisition opportunities, any products we acquire in the future may not have significant patent protection. Neither the USPTO nor the courts have a consistent policy regarding the breadth of claims allowed or the degree of protection afforded under many pharmaceutical patents. Patent applications in the U.S. and many foreign jurisdictions are typically not published until 18 months following the filing date of the first related application, and in some cases not at all. In addition, publication of discoveries in scientific literature often lags significantly behind actual discoveries. Therefore, neither we nor our licensors can be certain that we or they were the first to make the inventions claimed in our issued patents or pending patent applications, or that we or they were the first to file for protection of the inventions set forth in these patent applications. In addition, changes in either patent laws or in interpretations of patent laws in the U.S. and other countries may diminish the value of our intellectual property or narrow the scope of our patent protection. Furthermore, our competitors may independently develop similar technologies or duplicate technology developed by us in a manner that does not infringe our patents or other intellectual property. As a result of these factors, our patent rights may not provide any commercially valuable protection from competing products.

If we are unable to protect the confidentiality of our proprietary information and know-how, the value of our technology and products could be adversely affected.

In addition to patents, we rely upon trade secrets, unpatented proprietary know-how and continuing technological innovation where we do not believe patent protection is appropriate or attainable. For example, the manufacturing process for Kristalose involves substantial trade secrets and proprietary know-how. We have entered into confidentiality agreements with certain key employees and consultants pursuant to which such employees and

consultants must assign to us any inventions relating to our business if made by them while they are our employees, as well as certain confidentiality agreements relating to the acquisition of rights to products. Confidentiality agreements can be breached, though, and we might not have adequate remedies for any breach. Also, others could acquire or independently develop similar technology.

We may depend on certain licensors for the maintenance and enforcement of intellectual property rights and have limited, if any, control over the amount or timing of resources that our licensors devote on our behalf.

When we license products, we often depend on our licensors to protect the proprietary rights covering those products. We have limited, if any, control over the amount or timing of resources that our licensors devote on our behalf or the priority they place on maintaining patent or other rights and prosecuting patent applications to our advantage. While any such licensor is expected to be contractually obligated to diligently pursue its patent applications and allow us the opportunity to consult, review and comment on patent office communications, we cannot be sure that it will perform as required. If a licensor does not perform and if we do not assume the maintenance of the licensed patents in sufficient time to make required payments or filings with the appropriate governmental agencies, we risk losing the benefit of all or some of those patent rights.

If the use of our technology conflicts with the intellectual property rights of third parties, we may incur substantial liabilities, and we may be unable to commercialize products based on this technology in a profitable manner or at all.

If our products conflict with the intellectual property rights of others, they could bring legal action against us or our licensors, licensees, manufacturers, customers or collaborators. If we were found to be infringing a patent or other intellectual property rights held by a third party, we could be forced to seek a license to use the patented or otherwise protected technology. We might not be able to obtain such a license on terms acceptable to us or at all. If legal action involving an alleged infringement or misappropriation were to be brought against us or our licensors, we would incur substantial costs in defending the action. If such a dispute were to be resolved against us, we could be subject to significant damages, and the manufacturing or sale of one or more of our products could be enjoined.

We may be involved in lawsuits to protect or enforce our patents or the patents of our collaborators or licensors, which could be costly and time consuming.

We have been involved in lawsuits for infringement of the Acetadote Patents as previously described. Because of their nature, these lawsuits can be costly and time-consuming, and we only experience limited benefits and patent protection. A significant adverse ruling in any such lawsuit could put the Acetadote Patents at risk of being invalidated or interpreted narrowly and could compromise the issuance of our existing patent applications.

Competitors may infringe on our other patents or the patents of our collaborators or licensors. To counter infringement or unauthorized use, we may be required to file infringement claims, which can be expensive and time-consuming. In addition, in an infringement proceeding, a court may decide that a patent of ours is not valid or is unenforceable, or may refuse to stop the other party from using the technology at issue on the grounds that our patents do not cover the technology in question. An adverse result in any litigation or defense proceeding could put one or more of our patents at risk of being invalidated or interpreted narrowly and could put our patent applications at risk of not issuing.

Interference proceedings brought by the USPTO may be necessary to determine the priority of inventions with respect to our patent applications or those of our collaborators or licensors. Litigation or interference proceedings may fail and, even if successful, may result in substantial costs and distraction of our management. We may not be able, alone or with our collaborators and licensors, to prevent misappropriation of our proprietary rights, particularly in countries where the laws may not protect such rights as fully as in the United States.

Furthermore, because of the substantial amount of discovery required in connection with intellectual property litigation, some of our confidential information could be disclosed during this type of litigation. In addition, there could be public announcements of the results of hearings, motions or other interim proceedings or developments.

If we breach any of the agreements under which we license rights to our products and product candidates from others, we could lose the ability to continue commercialization of our products and development and commercialization of our product candidates.

We have exclusive licenses for the marketing and sale of certain products and may acquire additional licenses. Such licenses may terminate prior to expiration if we breach our obligations under the license agreement related to these pharmaceutical products. For example, the licenses may terminate if we fail to meet specified quality control standards, including GMP with respect to the products, or commit a material breach of other terms and conditions of the licenses. Such early termination could have a material adverse effect on our business, financial condition and results of operations.

We may be subject to claims that our employees have wrongfully used or disclosed alleged trade secrets of their former employers.

As is common in the biotechnology and pharmaceutical industry, we employ individuals who were previously employed at other biotechnology or pharmaceutical companies, including our competitors or potential competitors. Although no claims against us are currently pending, we may be subject to claims that we or these employees have inadvertently or otherwise used or disclosed trade secrets or other proprietary information of their former employers. Litigation may be necessary to defend against these claims. Even if we are successful in defending against these claims, litigation could result in substantial costs and be a distraction to management.

RISKS RELATED TO OUR FINANCIAL CONDITION AND RESULTS OF OPERATIONS

Our operating results are likely to fluctuate from period to period.

We are a company actively seeking to deliver significant growth. As we execute our business strategy of adding new products, increasing market share in our existing growth products and striving to maintain market share in our other products, we anticipate that there may be fluctuations in our future operating results. We may not be able to maintain or improve our current levels of revenue or income. Potential causes of future fluctuations in our operating results may include:

New product launches, which could increase revenues but also increase sales and marketing expenses;

Acquisition activity and other charges;

Increases in research and development expenses resulting from the acquisition of a product candidate that requires significant additional studies and development;

Ability to utilize unrecognized federal and state net operating loss carryforwards as a result of the exercise of nonqualified options

Changes in the competitive, regulatory or reimbursement environment, which could drive down revenues or drive up sales and marketing or compliance costs; e

Unexpected product liability or intellectual property claims and lawsuits.

See also 'Management's discussion and analysis of financial condition and results of operations-Liquidity and capital resources.' Fluctuation in operating results, particularly if not anticipated by investors and other members of the financial community, could add to volatility in our stock price.

Our focus on acquisitions as a growth strategy has created intangible assets whose amortization could negatively affect our results of operations.

Our total assets include intangible assets related to our acquisitions. As of December 31, 2019, intangible assets relating to products, which are being amortized, represented approximately 30% of our total assets. We may never realize the value of these assets. U.S. Generally Accepted Accounting Principles ('GAAP') require that we evaluate on a regular basis whether events and circumstances have occurred that indicate that all or a portion of the carrying amount of the asset may no longer be recoverable, in which case we would write down the value of the asset and

take a corresponding charge to earnings. Any determination requiring the write-off of a significant portion of unamortized intangible assets would adversely affect our results of operations.

We may need additional funding and may be unable to raise capital when needed, which could force us to delay, reduce or eliminate our product development or commercialization and marketing efforts.

We may need to raise additional funds in order to meet the capital requirements of running our business and acquiring and developing new pharmaceutical products. If we require additional funding, we may seek to sell common stock or other equity or equity-linked securities, which could result in dilution to our shareholders. We may also seek to raise capital through a debt financing, which would result in ongoing debt-service payments and increased interest expense. Any financings would also likely involve operational and financial restrictions being imposed on us. We might also seek to sell assets or rights in one or more commercial products or product development programs. Additional capital might not be available to us when we need it. We are unable to predict the impact of global credit market trends, and if economic conditions deteriorate, our business, results of operations and ability to raise needed capital could be materially and adversely affected. If we are unable to raise additional capital when needed due to the reasons listed above and lack of creditworthiness, bank failures, or price decline in market investments, we could be forced to scale back our operations to conserve cash.

If we are unable to maintain appropriate internal financial reporting controls and procedures, it could cause us to fail to meet our reporting obligations, result in the restatement of our financial statements, harm our operating results, subject us to regulatory scrutiny and sanction, cause investors to lose confidence in our reported financial information and have a negative effect on the market price for shares of our common stock.

Effective internal controls are necessary for us to provide reliable financial reports and mitigate the risk of fraud. We maintain a system of internal control over financial reporting, which is defined as a process designed by, or under the supervision of, our principal executive officer and principal financial officer, and affected by our board of directors, management and other personnel, to provide reasonable assurance regarding the reliability of financial reporting and the preparation of financial statements for external purposes in accordance with GAAP.

We cannot assure you that we will not, in the future, identify areas requiring improvement in our internal control over financial reporting. We cannot assure you that the measures we will take to improve these controls will be successful or that we will implement and maintain adequate controls over our financial processes and reporting in the future as we continue to expand. If we are unable to establish appropriate internal financial reporting controls and procedures, it could cause us to fail to meet our reporting obligations, result in the restatement of our financial statements, harm our operating results, subject us to regulatory scrutiny and sanction, cause investors to lose confidence in our reported financial information and have a negative effect on the market price for shares of our common stock.

In addition, we maintain a system of internal controls and provide training to employees designed to provide reasonable assurance that unlawful and fraudulent activity, including misappropriation of assets, fraudulent financial reporting, and unauthorized access to sensitive or confidential data is either prevented or timely detected. However, in the event that our employees engage in such fraudulent behavior, we could suffer material adverse consequences.

Changes in, or interpretations of, accounting principles and tax laws could have a significant impact on our financial position and results of operations.

We prepare our consolidated financial statements in accordance with GAAP. These principles are subject to interpretation by the SEC and various bodies formed to interpret and create appropriate accounting principles. A change in these principles can have a significant effect on our reported results and may even retroactively affect previously reported transactions.

For example, in recent years, the U.S.-based Financial Accounting Standards Board, ('FASB'), has worked together with the International Accounting Standards Board, ('IASB'), on several projects to further align accounting principles and facilitate more comparable financial reporting between companies who are required to follow GAAP under SEC regulations and those who are required to follow International Financial Reporting Standards, ('IFRS'), outside of the U.S. These efforts by the FASB and IASB may result in different accounting principles under GAAP that may result in materially different financial results for us in certain areas.

We may incur losses in the future and we may not achieve or maintain profitability.

We intend to continue to spend significant amounts on our efforts to discover and develop drugs. As a result, we may incur losses in future periods.

We anticipate that our drug discovery and development efforts and related expenditures will increase as we focus on the studies, including clinical trials prior to seeking regulatory approval, that are required before we can sell a drug product.

The development of drug products will require us to spend significant funds on research, development, testing, obtaining regulatory approvals, manufacturing and marketing.

We cannot be certain whether or when we will achieve profitability because of the significant uncertainties relating to our ability to generate commercially successful drug products. Even if we are successful in obtaining regulatory approvals for manufacturing and commercializing additional drug products, we may incur losses if our drug products do not generate significant revenues. If we achieve profitability, we may not be able to sustain or increase profitability.

We may seek to obtain future financing through the issuance of debt or equity, which may have an adverse effect on our shareholders or may otherwise adversely affect our business.

If we raise funds through the issuance of additional equity, whether through private placements or public offerings, such an issuance would dilute ownership of our current shareholders that do not participate in the issuance. If we are unable to obtain any needed additional funding, we may be required to reduce the scope of, delay, or eliminate some or all of, our planned research, development and commercialization activities or to license to third parties the rights to develop and/or commercialize products or technologies that we would otherwise seek to develop and/or commercialize ourselves or on terms that are less attractive than they might otherwise be, any of which could materially harm our business.

Furthermore, the terms of any additional debt securities we may issue in the future may impose restrictions on our operations, which may include limiting our ability to incur additional indebtedness, pay dividends on or repurchase our common shares, or make certain acquisitions or investments. In addition, we may be subject to covenants requiring us to satisfy certain financial tests and ratios, and our ability to satisfy such covenants may be affected by events outside of our control.

Our officers, directors, and principal shareholders, acting as a group, could significantly influence corporate actions.

As of December 31, 2019, our officers and directors control approximately 40 percent of our common stock. Acting together, these shareholders could significantly influence any matter requiring approval by our shareholders, including the election of directors and the approval of mergers or other business combinations. The interests of this group may not always coincide with our interests or the interests of other shareholders and may prevent or delay a change in control. This significant concentration of share ownership may adversely affect the trading price of our common stock because many investors perceive disadvantages to owning stock in companies with controlling shareholders.

Research analysts may not continue to provide or initiate coverage of our common stock or may issue negative reports.

The market for our common stock may be affected by the reports financial analysts publish about us. If one of the analysts covering us downgrades our stock, its price could decline rapidly and significantly. Securities analysts covering our common stock may discontinue coverage. A lack of research coverage may adversely affect our stock's market price.

RISKS RELATED TO OWNING OUR STOCK

The market price of our common stock may fluctuate substantially.

The price for the shares of our common stock sold in our initial public offering was determined by negotiation between the representatives of the underwriters and us. This price may not have reflected the market price of our common stock following our initial public offering. Through March 1, 2020, the closing price of our common stock since our initial public offering has ranged from a low of $4.03 to a high of $17.05 per share. Moreover, the market price of our common stock might decline below current levels. In addition, the market price of our common stock is likely to be highly volatile and may fluctuate substantially. Sales of a substantial number of shares of our common stock in the public market or the perception that these sales may occur could cause the market price of our common stock to decline.

The realization of any of the risks described in these 'Risk Factors' could have a dramatic and material adverse impact on the market price of our common stock. In addition, securities class action litigation has often been instituted against companies whose securities have experienced periods of volatility in market price. Any such securities litigation brought against us could result in substantial costs and a diversion of management's attention and resources, which could negatively impact our business, operating results and financial condition. Sales of a substantial number of shares of our common stock in the public market or the perception that these sales may occur could cause the market price of our common stock to decline.

Unstable market conditions may have serious adverse consequences on our business.

Our general business strategy may be adversely affected by unpredictable and unstable market conditions. While we believe we have adequate capital resources to meet current working capital and capital expenditure requirements, a radical economic downturn or increase in our expenses could require additional financing on less than attractive rates or on terms that are dilutive to existing shareholders. Failure to secure any necessary financing in a timely manner and on favorable terms could have a material adverse effect on our growth strategy, financial performance and stock price and could require us to delay or abandon clinical developments plans. There is a risk that one or more of our current service providers, manufacturers and other partners may encounter difficult economic circumstances, which would directly affect our ability to attain our operating goals on schedule and on budget.

We experience costs and regulatory risk as a result of operating as a public company, and our management is required to devote time to compliance initiatives.

We have and will continue to incur costs as a result of operating as a public company, and our management is required to devote time to compliance initiatives. As a public company, we have and will continue to incur legal, accounting and other expenses that we did not incur as a private company. In addition, the Sarbanes-Oxley Act of 2002, or Sarbanes-Oxley Act, Dodd-Frank Wall Street Reform and Consumer Protection Act of 2010, and other rules and regulations subsequently implemented by the SEC and NASDAQ, have imposed various requirements on public companies, including the establishment and maintenance of effective disclosure and financial controls and changes in corporate governance practices. These rules and regulations have and will continue to result in legal and financial compliance costs and render some activities more time-consuming and costly. Despite the internal controls and procedures put in place to maintain compliance with securities laws and regulations, our employees may still fail to comply with all SEC disclosure and reporting requirements. Such failure could lead to administrative and civil penalties, criminal penalties, and private litigation with shareholders. The consequences could have a material effect on our ability to effectively market our products and operate our business.

The Sarbanes-Oxley Act requires, among other things, that we maintain effective internal controls for financial reporting and disclosure controls and procedures. In particular, we must perform system and process evaluation and testing of our internal controls over financial reporting to allow management to report on the effectiveness of our internal controls over financial reporting. Our testing may reveal deficiencies in our internal controls over financial reporting that are deemed to be material weaknesses.

Our compliance with Section 404 of the Sarbanes-Oxley Act requires that we incur substantial accounting expense and expend significant management efforts. Moreover, if we are not able to comply with the requirements of Section 404 of the Sarbanes-Oxley Act in a timely manner, or if we identify deficiencies in our internal controls over financial reporting that are deemed to be material weaknesses, the market price of our stock could decline and we could be subject to sanctions or investigations by NASDAQ, the SEC or other regulatory authorities, which would require additional financial and management resources.

Some provisions of our third amended and restated charter, bylaws and Tennessee law may inhibit potential acquisition bids that you may consider favorable.

Our corporate documents contain provisions that may enable our board of directors to resist a change in control of our company even if a change in control were to be considered favorable by you and other shareholders. These provisions include:

The authorization of undesignated preferred stock, the terms of which may be established and shares of which may be issued without shareholder approval;

Advance notice procedures required for shareholders to nominate candidates for election as directors or to bring matters before an annual meeting of shareholders;

Limitations on persons authorized to call a special meeting of shareholders;

A staggered board of directors;

A restriction prohibiting shareholders from removing directors without cause;

A requirement that vacancies in directorships are to be filled by a majority of the directors then in office and the number of directors is to be fixed by the board of directors; e

No cumulative voting.

These and other provisions contained in our third amended and restated charter and bylaws could delay or discourage transactions involving an actual or potential change in control of us or our management, including transactions in which our shareholders might otherwise receive a premium for their shares over then current prices, and may limit the ability of shareholders to remove our current management or approve transactions that our shareholders may deem to be in their best interests and, therefore, could adversely affect the price of our common stock.

In addition, we are subject to control share acquisitions provisions and affiliated transaction provisions of the Tennessee Business Corporation Act, the applications of which may have the effect of delaying or preventing a merger, takeover or other change in control of us and therefore could discourage attempts to acquire our company.

We have never paid cash dividends on our capital stock.

We have never paid cash dividends on our capital stock. The availability of funds for distributions to shareholders will depend on our financial performance and assets. Any future decision to declare or pay dividends will be at the sole discretion of our Board of Directors

DEBT-RELATED RISKS

Our Revolving Credit Agreement impose restrictive and financial covenants on us. Our failure to comply with these covenants could trigger events that would have a material adverse effect on our business.

Our Revolving Credit Agreement contains covenants that restrict the way we conduct business and require us to satisfy certain financial tests in order to incur debt or take other actions. Additionally, our Revolving Credit Agreement contains financial covenants that, for example, require us to maintain certain financial ratios which are measured at the end of each fiscal quarter.

Our Revolving Credit Agreement contains specified quarterly financial maintenance covenants. As of December 31, 2019, we were in compliance with the Tangible Capital Ratio financial covenant of the Revolving Credit Agreement and we expect to maintain compliance with the Tangible Capital Ratio financial covenant in future periods. However, we can make no assurance that we will be able to comply with the restrictive and financial covenants contained in the Revolving Credit Agreement in the future.

Our inability to comply with the covenants in our debt instruments could lead to a default or an event of default under the terms thereof, for which we may need to seek relief from our lender in order to waive the associated default or event of default and avoid a potential acceleration of the related indebtedness or cross-default or cross-acceleration to other debt. There can be no assurance that we would be able to obtain such relief on commercially reasonable terms or otherwise and we may be required to incur significant additional costs. In addition, the lender under our Revolving Credit Agreement may impose additional operating and financial restrictions on us as a condition to granting any such waiver. If an event of default is not cured or is not otherwise waived, the lender under our Revolving Credit Agreement may accelerate the maturity of the related debt, foreclose upon any collateral securing the debt and terminate any commitments to lend, any of which would have a material adverse effect on our business, financial condition, cash flows and results of operations and would cause the market value of our securities to decline.

We have risks related to interest rates.

Our revolving credit facility bears interest based on variable interest. Thus, a change in the short-term interest rate environment (especially a material change) could have a material adverse effect on our business, financial condition, cash flows and results of operations. As of December 31, 2019, we did not have any outstanding interest rate swap contracts.

SPECIAL NOTE REGARDING FORWARD-LOOKING STATEMENTS

Statements in this Annual Report on Form 10-K that are not historical factual statements are 'forward-looking statements.' Forward-looking statements include, among other things, statements regarding our intent, belief or expectations, and can be identified by the use of terminology such as 'may,' 'will,' 'expect,' 'believe,' 'intend,' 'plan,' 'estimate,' 'should,' 'seek,' 'anticipate' and other comparable terms or the negative thereof. In addition, we, through our senior management, from time to time make forward-looking oral and written public statements concerning our expected future operations and other developments. While forward-looking statements reflect our good-faith beliefs and best judgment based upon current information, they are not guarantees of future performance and are subject to known and unknown risks and uncertainties, including those mentioned in Item 1A, 'Risk Factors,' Item 7, 'Management's Discussion and Analysis of Financial Condition and Results of Operations' and elsewhere in this Form 10-K. Accordingly, investors are cautioned not to place undue reliance on any forward-looking statements. Actual results may differ materially from the expectations contained in the forward-looking statements as a result of various factors. Such factors include, but are not limited to:

The possible or assumed future results of operations, including the accuracy of our estimates regarding expenses, future revenues, capital requirements and needs for additional financing;

Changes in national or regional economic conditions, including changes in interest rates and the availability and the cost of capital to us;

Our competitive position and competitors, including the size and growth potential of the markets for our products and product candidates;

The success, cost and timing of our product acquisition and development activities and clinical trials; and our ability to successfully commercialize our product candidates;

Product efficacy or safety concerns, whether or not based on scientific evidence, resulting in product withdrawals, recalls, regulatory action on the part of the FDA (or international counterparts) or declining sales;

The performance of our third-party suppliers and manufacturers which impacts our supply chain and could create business shutdowns or product shortages; and the retention of key scientific and management personnel;

Challenges to our patents and the introduction of generic versions of our products and product candidates, which could negatively impact our ability to commercialize and sell our products and product candidates and decrease sales a result of market exclusivity;

Changes in reimbursement available to us, including changes in Medicare and Medicaid payment levels and availability of third-party insurance coverage and the effects of future legislation or regulations, including changes to regulatory approval of new products, licensing and patent rights, environmental protection and possible drug re-importation legislation;

Interruptions and breaches of our computer and communications systems, and those of our vendors, including computer viruses, hacking and cyber-attacks, that could impair our ability to conduct business and communicate internally and with our customers, or result in the theft of trade secrets or other misappropriation of assets, or otherwise compromise privacy of sensitive information belonging to us, our customers or other business partners; e

Issuance of new or revised accounting standards by the Financial Accounting Standards Board and the Securities and Exchange Commission.

The list above contains many, but not all, of the factors that could impact our ability to achieve results described in any forward-looking statements. Investors should understand that it is not possible to predict or identify all such factors and should not consider this list to be a complete statement of all potential risks and uncertainties. We have identified the factors on this list as permitted by the Private Securities Litigation Reform Act of 1995.

Item 1B. Unresolved Staff Comments.

None.

Item 2. Properties.

As of December 31, 2019, we leased approximately 25,500 square feet of office space in Nashville, Tennessee for our corporate headquarters. The lease expires in October 2022. We believe these facilities are adequate to meet our current needs for office space. Manufacturing, packaging or warehousing services are provided to us through contracts with third-party organizations.

The laboratory space at CET, under an agreement amended in July 2012, is leased through April 2023, with an option to extend the lease through April 2028. CET leases approximately 14,200 square feet of office and wet laboratory space in Nashville, Tennessee to operate the CET Life Sciences Center. Cumberland's product formulation and testing laboratories are located at this facility, along with CET's offices. The CET Life Sciences Center also provides laboratory and office space, equipment and infrastructure to early-stage life sciences companies and university spin-outs.

Item 3. Legal Proceedings.

Please see the discussion of our Acetadote patent defense legal proceedings contained in Part 1, Item 1, Business -Patents, Trademarks and Other Intellectual Proprietary Rights, of this Form 10-K, which is incorporated by reference herein.

Item 4. Mine Safety Disclosures.

Not applicable.

PART II

Item 5. Market for Registrant's Common Equity, Related Stockholder Matters and Issuer Purchases of Equity Securities.

Market Information

Our common stock, no par value, has been traded on the Nasdaq Global Select Market since August 11, 2009 under the symbol 'CPIX.' As of March 16, 2020, we had 77 shareholders of record of our common stock. This excludes shareholders whose shares are held by brokers and other institutions on behalf of shareholders. The closing price of our common stock on the Nasdaq Global Select Market on March 16, 2020 was $3.98 per share.

Dividend Policy

We have not declared or paid any cash dividends on our common stock. Any future decision to declare or pay dividends will be at the sole discretion of our Board of Directors.

Performance Graph

The stock performance graph below illustrates a comparison of the total cumulative stockholder return on our common stock since December 31, 2014 to the Nasdaq Composite and a composite of seven Nasdaq Pharmaceutical and Specialty Pharmaceutical Stocks which most closely compare to our Company. The graph assumes an initial investment of $100 on December 31, 2014, and that all dividends were reinvested.

Purchases of Equity Securities

The Company currently has a share repurchase program to repurchase up to $10.0 million of our common stock pursuant to Rule 10b-18 of the Securities Act of 1934. In January 2019, the Company's Board of Directors established the current $10.0 million repurchase program to replace the prior authorizations. We repurchased 623,478 shares, 443,041 shares and 547,376 shares of common stock for approximately $3.5 million, $2.9 million, and $3.7 million during the years ended December 31, 2019, 2018 and 2017, respectively.

The following table summarizes the activity, by month, during the fourth quarter of 2019:

Periodo

Total Number

of Shares (or

Units)

Purchased

Average

Price Paid

per Share

(or Unit)

Total Number of

Shares (or

Units)

Purchased as

Part of Publicly

Announced

Plans or

Programs

Maximum Number (or

Approximate Dollar

Value) of Shares (or

Units) that May Yet Be

Purchased Under the

Plans or Programs

October 39,536 $5.64 39,536 $8,667,406
November 65,947 (1) $4.96 65,947 $8,340,247
December 65,840 $5.16 65,840 $8,000,709
Total 171,323

(1) Of this amount, 15,041 shares were repurchased directly in private purchases at the then-current fair market value of common stock.

Item 6. Selected Financial Data.

The selected consolidated financial data set forth below should be read in conjunction with the audited consolidated financial statements and related notes and Item 7, 'Management's Discussion and Analysis of Financial Condition and Results of Operations' and other financial information appearing elsewhere in this Form 10-K. The historical results are not necessarily indicative of the results to be expected for any future periods.

Years Ended December 31,
Statement of income data: 2019 2018 2017 2016 2015
(in thousands, except per share data)
Net revenues $ 47,534 $ 40,742 $ 41,150 $ 33,026 $ 33,519
Costs and expenses 51,157 48,133 45,231 34,459 32,407
Operating income (loss) (3,623) (7,391) (4,081) (1,433) 1,112
Net income (loss) attributable to common shareholders (3,538) (6,963) (7,979) (945) 731
Earnings (loss) per share – basic $ (0.23) $ (0.45) $ (0.50) $ (0.06) $ 0.04
Earnings (loss) per share – diluted $ (0.23) $ (0.45) $ (0.50) $ (0.06) $ 0.04
As of December 31,
Balance sheet data: 2019 2018 2017 2016 2015
(in thousands)
Cash and cash equivalents $ 28,213 $ 27,939 $ 45,413 $ 34,510 $ 38,203
Marketable securities 8,291 4,672 15,622 14,561
Working capital 26,013 31,312 50,990 50,753 52,172
Total assets 104,549 112,694 93,232 93,405 91,919
Total long-term debt (including current portion) and other long-term obligations 29,314 29,319 11,616 5,491 2,687
Retained earnings 1,208 4,746 11,709 18,605 19,550
Total equity 51,085 55,571 63,922 73,121 76,820

Item 7. Management's Discussion and Analysis of Financial Condition and Results of Operations.

The following discussion and analysis of our financial position and results of operations should be read together with our audited consolidated financial statements and related notes appearing elsewhere in this Form 10-K. This discussion and analysis may contain forward-looking statements that involve risks and uncertainties – please refer to the section entitled, 'Special Note Regarding Forward-Looking Statements,' contained in Part I, Item 1A, 'Risk Factors,' of this Form 10-K. You should review the 'Risk Factors' section of this Form 10-K for a discussion of important factors that could cause actual results to differ materially from the results described in or implied by the forward-looking statements described in the following discussion and analysis.

EXECUTIVE SUMMARY

We are a specialty pharmaceutical company focused on the acquisition, development and commercialization of branded prescription products. Our primary target markets are hospital acute care and gastroenterology. These medical specialties are characterized by relatively concentrated prescriber bases that we believe can be penetrated effectively by small, targeted sales forces. Cumberland is dedicated to providing innovative products that improve the quality of care for patients and address unmet or poorly met medical needs. We promote our approved products through our hospital and field sales forces in the United States and are establishing a network of international partners to bring our medicines to patients in their countries.

Our portfolio of FDA approved brands includes:

Acetadote®(acetylcysteine) Injection, for the treatment of acetaminophen poisoning;

Caldolor®(ibuprofen) Injection, for the treatment of pain and fever;

Kristalose®(lactulose) for Oral Solution, a prescription laxative, for the treatment of chronic and acute constipation;

Omeclamox®-Pak, (omeprazole, clarithromycin, amoxicillin) for the treatment of Helicobacter pylori (H. pylori) infection and related duodenal ulcer disease;

Vaprisol®(conivaptan) Injection, to raise serum sodium levels in hospitalized patients with euvolemic and hypervolemic hyponatremia;

Vibativ®(telavancin) Injection, for the treatment of certain serious bacterial infections including hospital-acquired and ventilator-associated bacterial pneumonia, as well as complicated skin and skin structure infections; e

RediTrex(methotrexate) Injection, for the treatment of active rheumatoid, juvenile idiopathic and severe psoriatic arthritis, as well as disabling psoriasis.

Additionally, we have Phase II clinical programs underway evaluating our ifetroban product candidates in patients with cardiomyopathy associated with Duchenne Muscular Dystrophy ('DMD'), Systemic Sclerosis ('SSc'), and Aspirin-Exacerbated Respiratory Disease ('AERD'). We have also completed Phase II clinical programs with ifetroban in patients with Hepatorenal Syndrome ('HRS') and patients with Portal Hypertension ('PH').

We promote our approved products through our hospital and gastroenterology sales forces in the United States, which together comprised approximately 40 sales representatives and managers as of December 31, 2019.

We have both product development and commercial capabilities and believe we can leverage our existing infrastructure to support our expected growth. Our management team consists of pharmaceutical industry veterans experienced in business development, product development, regulatory, manufacturing, sales marketing and finance. Our business development team identifies, evaluates and negotiates product acquisition, licensing and co-promotion opportunities. Our product development team creates proprietary product formulations, manages our clinical studies, prepares all regulatory submissions and manages our medical call center. Our quality and manufacturing

professionals oversee the manufacture, release and shipment of our products. Our marketing and sales professionals are responsible for our commercial activities, and we work closely with our distribution partners to ensure availability and delivery of our products.

The following is a summary of our 2019 highlights and recent developments. For more information, please see Part I, Item I, Attività commerciale, of this Form 10-K.

Early in 2019, we announced a strategic review of our brands, capabilities, and international partners. This review followed an accelerated business development initiative, which resulted in a series of transactions. Because of that progress, we felt that it was prudent to take a fresh look at our product portfolio, partners, and organization to ensure proper focus and capabilities.

We executed a License and Distribution agreement with HongKong WinHealth Pharma Group Co. Limited ('WinHealth') for our Caldolor and Acetadote brands in China and Hong Kong.

We also entered into a Strategic Alliance agreement with WinHealth to explore future business opportunities that will further the mission and goals of each organization.

We completed the assignment and amendment of a Commercialization Agreement with R-Pharma JSC ('R Pharma') associated with ongoing distribution of Vibativ in Russia and a number of adjacent countries in Eastern Europe.

We completed the assignment and amendment of a Commercialization Agreement with Hikma Pharmaceuticals LLC ('Hikma') to register and distribute Vibativ in a number of countries throughout the Middle East.

We also completed the assignment and amendment of a Commercialization Agreement with Dr. Reddy's Laboratories Limited ('Dr. Reddy's') for the registration and distribution of Vibativ in India.

We concluded our distribution and support for Ethyol and Totect at the end of 2019 and transitioned the responsibility for these products back to Clinigen.

Net revenue from sales of each of Caldolor, Omeclamox, Kristalose and Ethyol grew in 2019 compared to 2018.

In January 2019, the FDA approved the application for our next generation Caldolor product. In April 2019, we began initial shipments of the product to select customers. During the third and fourth quarters of 2019, there was a growing demand for the new product from these select accounts and we began planning for a full-scale launch in 2020.

In late 2019, we received FDA approval for RediTrex and began planning for a 2020 launch of this product line.

On September 24, 2019, Cumberland announced U.S. Food and Drug Administration ('FDA') Orphan Drug Grant funding for a new Phase II clinical program. The Company has initiated the clinical development of ifetroban for the treatment of cardiomyopathy associated with Duchenne Muscular Dystrophy ('DMD'). In addition, Cumberland has been awarded just over $1 million in funding from the FDA through their Orphan Drug Grant program to support this Phase II DMD clinical study.

In October 2019, a new study was published revealing the superiority of Vibativ (telavancin) over vancomycin in select patients with bacterial pneumonia.

In November 2019, we announced another study, published online in Drugs – Real World Outcomes, detailing the positive clinical outcomes that resulted from treating multiple infection types with Vibativ.

During 2019, Cumberland largely completed the transition of activities to support Vibativ, which Cumberland acquired from Theravance Biopharma during 2018.

CRITICAL ACCOUNTING POLICIES AND SIGNIFICANT JUDGMENTS AND ESTIMATES

Accounting Estimates and Judgments

The preparation of the consolidated financial statements in conformity with GAAP requires management to make estimates, judgments and assumptions that affect the reported amounts of assets and liabilities and disclosure of contingent liabilities at the date of the financial statements and the reported amounts of revenues and expenses during the period. We base our estimates on past experience and on other factors we deem reasonable given the circumstances. Past results help form the basis of our judgments about the carrying value of assets and liabilities that are not determined from other sources. Actual results could differ from these estimates. These estimates, judgments and assumptions are most critical with respect to our accounting for revenue recognition, marketable securities, inventory, intangible assets, research and development accounting, contingent consideration liability, provision for income taxes and share-based payments.

Revenue Recognition

We recognize revenue in accordance with the Accounting Standards Codification (ASC) Topic 606. Effective January 1, 2018, we adopted the Financial Accounting Standards Board's ('FASB') amended guidance in the form of Accounting Standards Update ('ASU') No. 2014-09, 'Revenue from Contracts with Customers,' (ASC 606). Results for reporting periods beginning after January 1, 2018 are presented under ASC 606, while prior period amounts were not adjusted and are reported in accordance with ASC 605.

Our revenue is derived primarily from the product sales of our FDA approved pharmaceutical brands. Revenue from sales of products is recognized at the point where the customer obtains control of the goods and we satisfy our performance obligation, which occurs upon either shipment of the product or arrival at its destination, depending upon the shipping terms of the transaction. Payment terms typically range from 30 to 60 days from date of shipment. Our net product revenue reflects the reduction from gross product revenue for estimated allowances for chargebacks, discounts and damaged goods, and reflects sales related accruals for rebates, coupons, product returns, and certain administrative and service fees. Significant judgments must be made in determining the transaction price for our sales of products related to these adjustments. Other revenue, which is a component of net revenues, includes non-refundable upfront payments and milestone payments under licensing agreements along with grant and rental income. Other income was approximately 4.2% percent of net revenues in 2019, 1.3% in 2018, and 1.9% in 2017 respectively.

Our financial statements reflect accounts receivable allowances of $0.8 million and $0.9 million at December 31, 2019 and 2018, respectively, for chargebacks, discounts and allowances for product damaged in shipment.

The following table reflects our sales-related accrual activity for the periods indicated below:

2019 2018 2017
Balance, January 1 $ 5,630,132 $ 4,683,694 $ 4,051,029
Current provision 15,042,658 13,603,177 12,318,312
Actual product returns and credits issued (15,847,133) (12,656,739) (11,685,647)
Balance, December 31 $ 4,825,657 $ 5,630,132 $ 4,683,694

The allowances for chargebacks, discounts, and damaged products and sales related accruals for rebates and product returns are determined on a product-by-product basis. We establish them using our best estimate at the time of sale based on:

Each product's historical experience adjusted to reflect known changes in the factors that impact such allowances;

The contractual terms with direct and indirect customers;

Analyses of historical levels of chargebacks, discounts and credits claimed for damaged and expired product;

Communications with customers;

Purchased information about the rate of prescriptions being written and the level of inventory remaining in the distribution channel, if known; e

Expectations about the market for each product, including any anticipated introduction of competitive products.

Other organizations, such as managed care providers, pharmacy benefit management companies and government agencies, may receive rebates from us based on either negotiated contracts to carry our products or reimbursements for filled prescriptions. These entities are considered our indirect customers. When recognizing a sale to a wholesaler, sales revenues are reduced and accrued liabilities are increased by our estimate of the rebate that may be claimed.

The allowances for chargebacks and accruals for rebates and product returns are the most significant estimates used in the recognition of our revenue from product sales. Of the accounts receivable allowances and our sales related accruals, our accrual for fee for services and product returns represents the majority of the balance. Sales related accrued liabilities for rebates, product returns, service fees, and administrative fees totaled $4.8 million, $5.6 million and $4.7 million as of December 31, 2019, 2018 and 2017, respectively. Of these amounts, our estimated liability for fee for services represented $1.6 million, $2.0 million and $1.5 million, respectively, while our accrual for product returns totaled $1.9 million, $2.2 million and $2.1 million, respectively. If the actual amount of cash discounts, chargebacks, rebates, and product returns differs from the amounts estimated by management, material differences may result from the amount of our revenue recognized from product sales. A change in our rebate estimate of one percentage point would have impacted net sales by approximately $0.4 million for the year ended December 31, 2019 and $0.3 million for the years ended December 31, 2018 and 2017, respectively. A change in our product return estimate of one percentage point would have impacted net sales by $0.5 million, $0.4 million and $0.4 million for the years ended December 31, 2019, 2018 and 2017, respectively.

Fair Value of Marketable Securities

We have historically invested a portion of our cash reserves in short-term cash investments, U.S. Treasury notes and bonds, corporate bonds and commercial paper in order to maximize our return on cash. We classify these investments as trading securities, and mark the investments to fair value at the end of each reporting period, with the adjustment being recognized in the statement of income as a component of interest income. These investments are generally valued using observable market prices by third-party pricing services, or are derived from such services' pricing models. The level of management judgment required in establishing fair value of financial instruments for which there is a quoted price in an active market is minimal. Similarly, there is little subjectivity or judgment required for instruments valued using valuation models that are standard across the industry and where all parameter inputs are quoted in active markets. Inputs to the models may include, but are not limited to, reported trades, executable bid and ask prices, broker/dealer quotations, prices or yields of securities with similar characteristics, benchmark curves or information pertaining to the issuer, as well as industry and economic events.

Inventories

We record amounts for estimated obsolescence or unmarketable inventory in an amount equal to the difference between the cost of inventory and the net realizable value based upon assumptions about remaining shelf life, future demand and market conditions. The estimated inventory obsolescence amounts are calculated based upon specific review of the inventory expiration dates and the quantity on-hand at December 31, 2019 in comparison to our expected inventory usage. The amount of actual inventory obsolescence and unmarketable inventory could differ (either higher or lower) in the near term from the estimated amounts. Changes in our estimates would be recorded in our statement of operations in the period of the change.

Income Taxes

We provide for deferred taxes using the asset and liability approach. Under this method, deferred tax assets and liabilities are recognized for the future tax consequences attributable to operating loss and tax credit carry-forwards and differences between the financial statement carrying amounts of existing assets and liabilities and their respective tax bases. Our principal differences are related to the timing of deductibility of certain items such as depreciation, amortization and expense for options issued to nonemployees. Deferred tax assets and liabilities are measured using management's estimate of tax rates expected to apply to taxable income in the years in which management believes those temporary differences are expected to be recovered or settled. The effect on deferred tax assets and liabilities of a change in tax rates is recognized in our results of operations in the period that includes the enactment date.

In assessing the realizability of deferred tax assets, management considers whether it is more likely than not that some portion or all of the deferred tax assets will not be realized. The ultimate realization of deferred tax assets is dependent upon the generation of future taxable income during the periods in which those temporary differences become deductible. Management considers the scheduled reversal of deferred tax liabilities, projected future taxable income and tax planning strategies in making this assessment.

We adopted FASB ASU 2016-09, 'Compensation – Stock Compensation: Improvements to Employee Share-Based Payment Accounting' effective January 1, 2017. The impact of adoption on our consolidated financial statements included the recording of $44.1 million in previously unrecognized net operating loss carryforwards, net of valuation allowances, generated from the exercise of nonqualified options during 2009. These net operating loss carryforwards occurred as a result of the actual tax benefit realized upon employee exercise exceeding the cumulative book compensation charge associated with the options.

The adoption resulted in the recording of $1.1 million in net non-current deferred tax assets and retained earnings effective as of January 1, 2017. The $1.1 million in net non-current deferred tax assets was the result of a deferred tax asset of $17.0 million, net of a related valuation allowance of $15.9 million. Under the previous accounting guidance, these benefits had been recognized in the year in which they were able to reduce current income taxes payable and we recorded these benefits directly to equity. As part of our adoption of the FASB guidance and its continued evaluation of our utilization of net operating loss carryforwards and other deferred tax assets, including updates to our forecasts of future taxable income, we also recorded an additional valuation allowance of $1.0 million for our federal Orphan Drug and Research and Development tax credits that expire between 2021 and 2036.

During the second quarter of 2017, as part of our continued evaluation of the utilization of our net operating loss carryforwards we recorded an additional valuation allowance of $3.5 million for our remaining deferred tax assets. All deferred tax assets have a full valuation allowance.

The net operating loss carryforwards generated during 2009 consisted of $44.1 million in federal and $45.4 million in state amounts. Since they were generated, we have utilized these net operating loss carryforwards to pay minimal income taxes. We will continue to experience a reduction in income taxes paid in future years, through the continued utilization of these net operating loss carryforwards, as we are able to achieve taxable income through our operations.

The Company's accounting policy with respect to interest and penalties arising from income tax settlements is to recognize them as part of the provision for income taxes.

On December 22, 2017, the Tax Cut and Jobs Act (the 'Tax Act') was signed into law. The Tax Act provides for significant changes in the U.S. Internal Revenue Code of 1986, as amended. The Tax Act contains provisions with separate effective dates but is generally effective for taxable years beginning after December 31, 2017. Certain provisions of the Tax Act were effective during our fiscal year ending December 31, 2018 with all provisions of the Tax Act effective as of the beginning of our fiscal year ending December 31, 2019.

Under ASC Topic 740, Income Taxes ('ASC 740'), we are required to revalue any deferred tax assets or liabilities in the period of enactment of change in tax rates. The Tax Act lowers the corporate income tax rate from

35% to 21%. As a result of the Tax Act discussed above, we will experience a positive impact to our future results of operations to the extent we achieve taxable income through our operations.

Share-Based Payments

We recognize compensation expense for all share-based payments based on the fair value of the award on the date of grant. In addition, incremental compensation expense is recognized upon the modification of equity awards.

We issue restricted stock awards at no cost in lieu of stock options to employees, directors and consultants. Compensation expense for restricted stock granted to employees and directors is generally equal to the fair market value of the underlying common stock on the date of grant. If a sufficient disincentive for nonperformance does not exist at the date of grant, the compensation cost is remeasured at each reporting date at the then-current fair market value of the underlying common stock until the award vests.

Research and Development

We accrue for and expense research and development costs based on estimates of work performed, patient enrollment or fixed-fee-for-services. As work is performed and/or invoices are received, we adjust our estimates and accruals. To date, our accruals have not differed materially from our estimates. Total research and development costs are a function of studies being conducted and will increase or decrease based on the level of activity in any particular year.

Intangible Assets and Goodwill

Intangible assets include product rights, license agreements, other identifiable intangible assets and goodwill associated with the Vibativ acquisition. We assess the impairment of goodwill at least annually. We assess the impairment of identifiable intangible assets subject to amortization whenever events or changes in circumstances indicate the carrying value may not be recoverable. In determining the recoverability of our intangible assets, we make assumptions regarding estimated future cash flows and other factors. If the estimated undiscounted future cash flows do not exceed the carrying value of the intangible assets, we must determine the fair value of the intangible assets. If the fair value of the intangible assets is less than the carrying value, an impairment loss will be recognized in an amount equal to the difference. Fair value is determined through various valuation techniques including quoted market prices, third-party independent appraisals and discounted cash flow models, as considered necessary.

RESULTS OF OPERATIONS

Year ended December 31, 2019 compared to year ended December 31, 2018

The following table presents the statements of operations for the years ended December 31, 2019 and 2018:

Years ended December 31,
2019 2018 Change
Net revenues $ 47,533,637 $ 40,741,765 $ 6,791,872
Costs and expenses:
Cost of products sold 8,752,020 7,378,095 1,373,925
Selling and marketing 21,429,040 20,258,307 1,170,733
Research and development 6,478,592 7,575,892 (1,097,300)
General and administrative 10,362,433 10,150,777 211,656
Amortization 4,134,557 2,769,466 1,365,091
Total costs and expenses 51,156,642 48,132,537 3,024,105
Operating income (loss) (3,623,005) (7,390,772) 3,767,767
Interest income 243,364 564,484 (321,120)
Interest expense (246,186) (195,848) (50,338)
Income (loss) before income taxes (3,625,827) (7,022,136) 3,396,309
Income tax (expense) benefit 79,316 (16,636) 95,952
Net income (loss) $ (3,546,511) $ (7,038,772) $ 3,492,261

The following table summarizes net revenues for the years presented:

Years ended December 31,
2019 2018 Change
Products:
Acetadote $ 3,824,449 $ 4,284,111 $ (459,662)
Omeclamox-Pak 837,829 623,297 214,532
Kristalose 12,895,120 12,055,625 839,495
Vaprisol 936,615 1,763,874 (827,259)
Caldolor 5,222,281 5,001,997 220,284
Ethyol 12,774,831 10,545,906 2,228,925
Totect 369,912 850,965 (481,053)
Vibativ 8,691,550 5,075,057 3,616,493
Other 1,981,050 540,933 1,440,117
Total net revenues $ 47,533,637 $ 40,741,765 $ 6,791,872

Net revenues.Net revenues for the year ended December 31, 2019 were approximately $47.5 million compared to $40.7 million for the year ended December 31, 2018, representing an increase of $6.8 million or 16.7%. Five of our products, Omeclamox-Pak, Kristalose, Caldolor, Vibativ and Ethyol, experienced an increase in revenue during 2019. The 16.7% improvement was led by our newest product, Vibativ, which delivered an additional $3.6 million during the full year of 2019 compared to a partial year during 2018.

These increases were partially offset by decreased net product sales of Acetadote, Vaprisol and Totect.

Kristalose revenue increased by $0.8 million, or 7.0%, compared to December 31, 2018 primarily as a result of increased wholesale prices. The product's net revenue was also positively impacted by lower managed care rebates, resulting in improved net pricing for the product for the year ended December 31, 2019.

Caldolor revenue experienced a 4.4% increase to $5.2 million during the year ended December 31, 2019 compared to $5.0 million in the same period last year. This increase in Caldolor revenue for the year ended December 31, 2019 was the result of an 11% increase in domestic shipments of the product and improved net pricing. These changes were partially offset by a reduction in international shipments of Caldolor when compared to the same period last year.

Ethyol revenue for the year ended December 31, 2019 was $12.8 million, which is an increase of $2.2 million or 21.1% from the year ended December 31, 2018. The increase in net revenue is primarily a result of increases in sales volumes and improved net pricing, including a reduction in chargeback deductions related to the Public Health Service's 340B drug pricing program.

Omeclamox-Pak revenue increased $0.2 million or 34.4% during the year ended December 31, 2019 compared to the prior year. The increase was largely the result of increased sales volume partially offset by higher expired product sales returns.

Vaprisol revenue decreased $0.8 million during the year ended December 31, 2019 compared to the prior year period due primarily to decreased sales of the product. The prior year period sales were higher as a result of the arrival of a new lot of the product during April 2018 resolving temporary supply issues associated with the product.

Totect revenue decreased $0.5 million for the year ended December 31, 2019 compared to the prior year. The decrease is primarily due to a decrease in product sales volume compared to the prior year period.

Acetadote revenue included net sales of our branded product and our share of net sales from our Authorized Generic. For the year ended December 31, 2019, the Acetadote net revenue decreased $0.5 million or 10.7% compared to the prior year due to a reduction in sales volume as a result of generic competition.

Cost of products sold. Cost of products sold for the year ended December 31, 2019 were $8.8 million, compared to $7.4 million in the prior year. As a percentage of net revenues, cost of products sold were 18.4% compared to 18.1% during the prior year. The improvement in costs of products sold as a percentage of revenue was attributable to a change in the product sales mix during the period compared to the prior year.

Selling and marketing. Selling and marketing expense for the year ended December 31, 2019 were $21.4 million, which was an increase of $1.2 million compared to the prior year's expense of $20.3 million. This increase was primarily attributable to promotional spending and sales force costs, including salary and benefits for the increased sales force. The increase in the sales force and promotional spending is due largely to the addition of our newest brand, Vibativ, during the fourth quarter of 2018.

Research and development. Research and development costs for the year ended December 31, 2019 were $6.5 million, compared to $7.6 million last year, representing a decrease of $1.1 million. A portion of our research and development costs are variable based on the number of trials, study sites and patients involved in the development of our product candidates. The decrease was primarily the result of the FDA program fee of $1.3 million paid during 2018 associated with the successful RediTrex FDA submission.

General and administrative. General and administrative expense for the year ended December 31, 2019 was $10.4 million for 2019, compared to $10.2 million last year. The $0.2 million or, 2.1%, increase from the same period for the prior year was primarily driven by an increase in compensation and benefits, including non-cash stock based compensation and deferred compensation.

Amortization.Amortization expense is the ratable use of our capitalized intangible assets including product and license rights, patents, trademarks and patent defense costs. Amortization for 2019 totaled approximately $4.1 million, which was an increase of $1.4 million over the prior year. The increase in expense was attributable to the amortization of additional product rights and capitalized patents, including those assets associated with the Vibativ acquisition.

Income taxes. Income tax benefit for the year ended December 31, 2019 was $79,316. As a percentage of income (loss) before income taxes, income taxes were a benefit of 2.2% for the year ended December 31, 2019 compared to income tax expense as a percentage of loss before income taxes of 0.2% for the year ended December 31, 2018.

Year ended December 31, 2018 compared to year ended December 31, 2017

The following table presents the statements of operations for the years ended December 31, 2018 and 2017:

Years ended December 31,
2018 2017 Change
Net revenues $ 40,741,765 $ 41,150,131 $ (408,366)
Costs and expenses:
Cost of products sold 7,378,095 7,370,585 7,510
Selling and marketing 20,258,307 21,492,937 (1,234,630)
Research and development 7,575,892 4,280,385 3,295,507
General and administrative 10,150,777 9,651,350 499,427
Amortization 2,769,466 2,436,222 333,244
Total costs and expenses 48,132,537 45,231,479 2,901,058
Operating income (loss) (7,390,772) (4,081,348) (3,309,424)
Interest income 564,484 299,326 265,158
Interest expense (195,848) (92,904) (102,944)
Income (loss) before income taxes (7,022,136) (3,874,926) (3,147,210)
Income tax (expense) benefit (16,636) (4,174,889) 4,158,253
Net income (loss) $ (7,038,772) $ (8,049,815) $ 1,011,043
Years ended December 31,
2018 2017 Change
Products:
Acetadote $ 4,284,111 $ 6,576,720 $ (2,292,609)
Omeclamox-Pak 623,297 1,761,868 (1,138,571)
Kristalose 12,055,625 11,455,805 599,820
Vaprisol 1,763,874 1,576,222 187,652
Caldolor 5,001,997 4,178,443 823,554
Ethyol 10,545,906 10,835,038 (289,132)
Totect 850,965 3,992,467 (3,141,502)
Vibativ 5,075,057 5,075,057
Other 540,933 773,568 (232,635)
Total net revenues $ 40,741,765 $ 41,150,131 $ (408,366)

Net revenues.Net revenues for the year ended December 31, 2018 were approximately $40.7 million compared to $41.2 million for the year ended December 31, 2017, representing a decrease of $0.4 million or 1.0%. Three of our products: Acetadote, Omeclamox-Pak and Totect experienced a decrease in revenue during 2018, with the largest decrease coming from our Totect product. We began shipments of Totect during a national shortage of dexrazoxane, resulting in strong initial demand for the product. Following our launch, supplies of dexrazoxane became available from competing suppliers.

These decreases were partially offset by the initial product sales of our newest product, Vibativ, as well as three of our marketed products experienced increases in net revenue during the period: Kristalose, Vaprisol and Caldolor.

Kristalose revenue increased by $0.6 million, or 5.2%, compared to December 31, 2017 primarily as a result of increased sales volume. The product's net revenue was positively impacted by increased sales volumes and lower managed care and Medicare rebates, that resulted in improved net pricing for the product for the year ended December 31, 2018.

Caldolor revenue experienced a 20% increase to $5.0 million during the year ended December 31, 2018 compared to $4.2 million in the same period last year. This increase in Caldolor revenue for the year ended December 31, 2018 was positively impacted by increased domestic and international shipments. Domestic net revenue improved from increased sales volumes and improved pricing.

Vaprisol revenue increased $0.2 million during the year ended December 31, 2018 compared to the prior year period due to increased sales of the product. Sales of Vaprisol surged during the second quarter of 2018 due to shipments of newly arrived inventory following a period of time when there were limited supplies of the product. During April 2018, the Vaprisol supply issue was resolved as we received new shipments from our manufacturer. The 12% net revenue increase was partially offset by an increase in expired product sales returns during the period.

Ethyol revenue for the year ended December 31, 2018 was $10.5 million, which was a decrease of $0.3 million from the year ended December 31, 2017. The decrease in net revenue was primarily a result of increases in chargeback deductions related to the Public Health Service's 340B drug pricing program.

Totect revenue decreased $3.1 million for the year ended December 31, 2018 compared to the prior year. The decrease was primarily due to a decrease in product sales volume compared to the prior year period.

Omeclamox-Pak revenue decreased $1.1 million during the year ended December 31, 2018 compared to the prior year. The decrease was largely the result of lower sales volume and much higher expired product sales returns.

Acetadote revenue included net sales of our branded product and our share of net sales from our Authorized Generic. For the year ended December 31, 2018, the Acetadote net revenue decreased $2.3 million compared to the prior year due to a reduction in sales volume as a result of generic competition.

Cost of products sold. Cost of products sold for the year ended December 31, 2018 were $7.4 million, remaining consistent with the prior year. As a percentage of net revenues, cost of products sold were 18.1% compared to 17.9% during the prior year. The change in costs of products sold as a percentage of revenue was attributable to a change in the product sales mix during the period compared to the prior year.

Selling and marketing. Selling and marketing expense for the year ended December 31, 2018 were $20.3 million, which was a decrease of $1.2 million compared to the prior year's expense of $21.5 million. The decrease was primarily attributable to lower royalty expense related to product sales as well as lower promotional spending for the year ended December 31, 2018.

Research and development. Research and development costs for the year ended December 31, 2018 were $7.6 million, compared to $4.3 million last year, which represented an increase of $3.3 million. A portion of our research and development costs are variable based on the number of trials, study sites and patients involved in the development of our product candidates. The increase was partially the result of additional investments in our ongoing clinical initiatives associated with our pipeline products of $1.6 million. There was also an increase in our products FDA program fees including the $1.3 million fee associated with our RediTrex submission. Research and development costs also increased for salary, wages and benefits.

General and administrative. General and administrative expense for the year ended December 31, 2018 was $10.2 million for 2018, compared to $9.7 million last year. The $0.5 million or, 5.2%, increase from the prior year was primarily driven by an increase in compensation and benefits along with increases in legal and consulting expenses.

Amortization.Amortization expense is the ratable use of our capitalized intangible assets including product and license rights, patents, trademarks and patent defense costs. Amortization for 2018 totaled approximately $2.8 million, which was an increase of $0.3 million over the prior year. The increase in amortization was attributable to additional product and license rights and capitalized patents.

Income tax expense. Income tax expense for the year ended December 31, 2018 was $16,636, compared to approximately $4.2 million in the year ended December 31, 2017. As a percentage of income (loss) before income taxes, income taxes were 0.2% for the year ended December 31, 2018 compared to 107.7% for the year ended December 31, 2017. As discussed in our consolidated financial statements, the effective tax rate for the year ended December 31, 2017 was primarily impacted by recording a valuation allowance of $1.0 million for our federal Orphan Drug and Research and Development tax credits and an additional valuation allowance of $3.5 million for our remaining deferred tax assets. These non-cash valuation allowance adjustments impacted our effective tax rate during the year ended December 31, 2017 . Ethyol revenue for the year ended December 31, 2017 was $10.8 million, which is an increase of $10.0 million from the year ended December 31, 2016. The Company began generating revenue from the sale of Ethyol during the third quarter of 2016. The increase resulted from a full year of sales of the product as well as increased demand for our branded Ethyol product during 2017.

LIQUIDITY AND CAPITAL RESOURCES

Our primary sources of liquidity are cash flows provided by our operations, the amounts borrowed and available under our line of credit and the cash proceeds from our initial public offering of common stock that was completed in August 2009. We believe that our internally generated cash flows, existing working capital and our line of credit, including its recent expansion to $20 million, will be adequate to finance internal growth, finance business development initiatives, and fund capital expenditures for the foreseeable future.

We invest a portion of our cash reserves in marketable securities including short-term cash investments, U.S. Treasury notes and bonds, corporate bonds, commercial paper and other marketable securities. At December 31, 2019, all our investments were in commercial paper with maturity dates under thirty days and classified as cash. At December 31, 2018, we had approximately $8.3 million invested in marketable securities.

The following table summarizes our liquidity and working capital as of the years ended December 31:

2019 2018
Cash and cash equivalents $ 28,212,635 $ 27,938,960
Marketable securities 8,290,679
Total cash, cash equivalents and marketable securities $ 28,212,635 $ 36,229,639
Working capital (current assets less current liabilities) $ 26,012,840 $ 31,311,813
Current ratio (multiple of current assets to current liabilities) 2.1 2.1
Revolving line of credit availability $ 1,500,000 $

The following table summarizes our net changes in cash and cash equivalents for the years ended December 31:

2019 2018 2017
Cash provided by (used in):
Operating activities $ 3,056,356 $ 3,112,737 $ (557,714)
Investing activities 2,297,848 (27,724,818) 9,512,577
Financing activities (5,080,529) 7,138,173 1,947,675

Net (decrease) increase in cash and

cash equivalents

$ 273,675 $ (17,473,908) $ 10,902,538

The net $0.3 million increase in cash and cash equivalents for the year ended December 31, 2019 was attributable to cash provided by operating and investing activities offset by cash used in financing activities. Cash provided by operating activities of $3.1 million included non-cash expense add backs for depreciation and amortization and share-based compensation expense totaling $5.9 million. This increase was partially offset by a net loss for the period of $3.5 million and changes in our working capital that used net cash of $1.4 million. Cash provided by investing activities of $2.3 million included net sales of marketable securities of $8.3 million, partially offset by the $5 million payment to Theravance as part of the acquisition of Vibativ and the addition to intangibles of $0.8 million. Our financing activities included a net repayment of $1.5 million under our line of credit net and $3.5 million in cash used to repurchase shares of our common stock.

As noted above, we continue to repurchase shares of our common stock, as discussed in Part II, Item 5, 'Market for Registrant's Common Equity, Related Stockholder Matters and Issuer Purchases of Equity Securities',of this Form 10-K.

The net $17.5 million decrease in cash and cash equivalents for the year ended December 31, 2018 was attributable to cash used by investing activities offset by cash provided by operating and financing activities. Cash provided by operating activities of $3.1 million was impacted by a net loss for the period of $7.0 million. This use of operating cash was offset by non-cash expenses of depreciation and amortization and share-based compensation expense totaling $4.3 million. Changes in our working capital provided net cash of $5.9 million. Cash used in investing activities included $20 million in cash paid for the acquisition of Vibativ during 2018, the use of cash to complete a net increase in marketable securities of $3.4 million, and the addition to intangibles of $3.8 million. Our financing activities included $10.2 million in net cash provided by borrowings under our line of credit net of $2.9 million in cash used to repurchase shares of our common stock.

The net $10.9 million increase in cash and cash equivalents for the year ended December 31, 2017 was attributable to cash provided by investing and financing activities offset by cash used in operating activities. Cash used in operating activities of $0.6 million was primarily impacted by a net loss for the period of $8.0 million. These uses of operating cash were offset by deferred tax expenses of $4.2 million and non-cash expenses of depreciation and amortization and share-based compensation expense totaling $4.1 million. Changes in our working capital used net cash of $0.8 million, including accounts receivable, inventory and other current assets of $3.5 million offset by cash provided by accounts payable increases of $2.3 million. Cash provided by investing activities included net proceeds from marketable securities of $11.0 million offset by additions to intangibles of $1.2 million. Our financing activities included $24.5 million in cash provided by borrowings under our line of credit and $3.7 million in cash used to repurchase shares of our common stock.

Shelf Registration

In November 2017, the Company filed its Shelf Registration on Form S-3 with the SEC associated with the sale of up to $100 million in corporate securities. The Shelf Registration which was declared effective in January 2018. It also included an At the Market ('ATM') feature that allows the Company to sell common shares at market prices, along with an agreement with B. Riley FBR to support such a placement of shares. The Company did not issue any shares under this ATM during the year ended December 31, 2019.

Debt Agreement

On May 10, 2019, we entered into a third amendment ('Third Amendment') to the Revolving Credit Loan Agreement, dated July 28, 2017, with Pinnacle Bank ('Pinnacle Agreement'). The Third Amendment extended the term of the Pinnacle Agreement through July 31, 2021 as well as modified certain definitions and terms of the existing financial covenants. On October 17, 2018, we entered into a second amendment ('Second Amendment') which increased the maximum aggregate principal available for borrowing under the Pinnacle Agreement to $20.0 million. For a summary of the material terms of the Pinnacle Agreement, as amended, see Note 9 to the accompanying notes to consolidated financial statements.

Under the Pinnacle Agreement, we were initially subject to one financial covenant, the maintenance of a Funded Debt Ratio, as such term is defined in the agreement and determined on a quarterly basis. On August 14, 2018 we amended the Pinnacle Agreement ('First Amendment') to replace the single financial covenant with the maintenance of either the Funded Debt Ratio or a Tangible Capital Ratio, as defined in the First Amendment. The Third Amendment modified the definition of the Funded Debt Ratio and the compliance target of the Tangible Capital Ratio. Both Third Amendment modifications were related to the Vibativ transaction. We were in compliance with the Tangible Capital Ratio financial covenant as of December 31, 2019 and we expect to maintain compliance with the Tangible Capital Ratio financial covenant in future periods.

Minimum Product Purchase Requirements

Our manufacturing and supply agreements do not require minimum annual purchase obligations.

Contractual cash obligations

The following table summarizes our contractual cash obligations as of December 31, 2019:

Payments Due by Year

Contractual obligations(1)

Total

2020 2021 2022 2023 2023 and thereafter

Line of credit(2)

$ 18,500,000 $ $ 18,500,000 $ $ $

Estimated interest on debt (2)

1,248,750 832,500 416,250

Contingent consideration liability payments (3)

8,633,589 2,114,040 1,139,617 997,491 735,405 3,647,036
Operating leases 3,376,746 1,120,066 1,144,889 1,019,313 92,478

Purchase obligations (4)

Total (1)

$ 31,759,085 $ 4,066,606 $ 21,200,756 $ 2,016,804 $ 827,883 $ 3,647,036

1.The sum of the individual amounts may not agree due to rounding.

2.The line of credit payments represent the estimated unused line of credit payments and the amount due at maturity. The estimated interest on debt represents the interest on the principal outstanding on the line of credit. These amounts are based on the $18.5 million line of credit assuming the current $18.5 million balance outstanding on December 31, 2019 is consistently outstanding through maturity of July 2021. Interest and unused line of credit payments are due and payable quarterly in arrears.

3.The contingent consideration liability represents the fair value of the royalty payments of up to 20% of future net sales as part of the Vibativ acquisition.

4.Represents minimum purchase obligations under our manufacturing agreements.

OFF-BALANCE SHEET ARRANGEMENTS

During 2019, 2018 and 2017, we did not engage in any off-balance sheet arrangements.

RECENT ACCOUNTING PRONOUNCEMENTS

Recent Adopted Accounting Pronouncements

In May 2014, the FASB issued amended guidance in the form of ASU No. 2014-09, 'Revenue from Contracts with Customers' ('ASC 606'). The core principle of the new guidance is to recognize revenues when promised goods or services are transferred to customers in an amount that reflects the consideration to which an entity expects to be entitled for those goods or services. The new guidance defines a five-step process to achieve this core principle and, in doing so, additional judgments and estimates may be required within the revenue recognition process. The new standard replaced most of the existing revenue recognition standards in U.S. GAAP when it became effective. In July 2015, the FASB issued a one-year deferral of the adoption date, which extended the effective date for us to January 1, 2018, at which point Cumberland adopted the standard.

The Company evaluated its revenues and the new guidance had immaterial impacts to recognition practices upon adoption on January 1, 2018. As part of the adoption, the Company elected to apply the new guidance on a modified retrospective basis. We did not record a cumulative effect adjustment to historical retained earnings for initially applying the new guidance as no revenue recognition differences were identified in the timing or amount of revenue.

In February 2016, the Financial Accounting Standards Board ('FASB') issued guidance in the form of a FASB Accounting Standards Update ('ASU') No. 2016-02, 'Leases.' The new standard establishes a right-of-use ('ROU') model that requires a lessee to record an ROU asset and a lease liability on the balance sheet for all leases with terms longer than twelve months. Leases will be classified as either finance (formerly 'capital leases') or operating, with classification affecting the pattern of expense recognition in the income statement. The standard provides for a modified retrospective transition approach for lessees for capital and operating leases existing at, or entered into after, the beginning of the earliest comparative period presented in the financial statements, with certain optional practical expedients. In July 2018, the FASB issued ASU 2018-11, 'Leases: Targeted Improvements', allowing for an alternative transition method (the effective date approach). It allows an entity to initially apply the new lease guidance at the adoption date (rather than at the beginning of the earliest period presented). Cumberland adopted the lease guidance effective January 1, 2019 using the package of transition practical expedients. This allowed us to retain the lease classification for any leases existing prior to adoption, in addition to other benefits.

Recent Accounting Pronouncements – Not Yet Adopted

In June 2016, the FASB issued ASU No. 2016-13, 'Financial Instruments-Credit Losses,' which changes the impairment model for most financial assets and certain other instruments. For trade and other receivables, held-to-maturity debt securities, loans and other instruments, companies will be required to use a new forward-looking 'expected loss' model that generally will result in the earlier recognition of allowances for losses. Companies will apply the standard's provisions as a cumulative-effect adjustment to retained earnings as of the beginning of the first reporting period in which the guidance is adopted. This standard is effective for Cumberland on January 1, 2020. We continue to evaluate this new standard on our trade and other receivables but do not expect a material impact on our consolidated financial statements.

In May 2019, the FASB issued ASU 2019-05, 'Financial Instruments-Credit Losses (Topic 326): Targeted Transition Relief' which provides transition relief for ASU 2016-13 by providing entities with an alternative to irrevocably elect the fair value option for eligible financial assets measured at amortized cost upon adoption of the new credit losses standard. Certain eligibility requirements must be met, the election must be applied on an instrument-by-instrument basis, and the election is not available for either available-for-sale or held-to-maturity debt securities. The effective date is the same as ASU 2016-13, January 1, 2020. We continue to evaluate this new standard on our trade and other receivables but do not expect a material impact on our consolidated financial statements.

In November 2018, the FASB issued ASU No. 2018-18, 'Collaboration Arrangements: Clarifying the Interaction between Topic 808 and Topic 606' (ASU 2018-18). The issuance of ASU 2014-09 raised questions about the interaction between the guidance on collaborative arrangements and revenue recognition. ASU 2018-18 addresses this uncertainty by (1) clarifying that certain transactions between collaborative arrangement participants should be accounted for as revenue under ASU 2014-09 when the collaboration arrangement participant is a customer, (2) adding unit of account guidance to assess whether the collaboration arrangement or a part of the arrangement is with a customer and (3) precluding a company from presenting transactions with collaboration arrangement participants that are not directly related to sales to third parties together with revenue from contracts with customers. The new standard will be effective for Cumberland on January 1, 2020. We continue to evaluate this new standard on our trade and other receivables but do not expect a material impact on our consolidated financial statements.

In January 2017, the FASB issued ASU No. 2017-04, 'Simplifying the Test for Goodwill Impairment' (ASU 2017-04). The guidance removes Step 2 of the goodwill impairment test, which requires a hypothetical purchase price allocation. As a result of the revised guidance, a goodwill impairment will be the amount by which a reporting unit's carrying value exceeds its fair value, not to exceed the carrying amount of goodwill. The new standard will be effective for Cumberland on January 1, 2020. We continue to evaluate this new standard but do not expect a material impact on our consolidated financial statements and related disclosures.

Item 7A. Quantitative and Qualitative Disclosures About Market Risk.

Interest Rate Risk

We are exposed to market risk related to changes in interest rates on our cash on deposit in highly-liquid money market accounts and revolving credit facility. We do not utilize derivative financial instruments or other market risk-sensitive instruments to manage exposure to interest rate changes. The main objective of our cash investment activities is to preserve principal while maximizing interest income through low-risk investments. Our investment policy focuses on principal preservation and liquidity.

We believe that our interest rate risk related to our cash and cash equivalents is not material. The risk related to interest rates for these accounts would produce less income than expected if market interest rates fall. Based on current interest rates, we do not believe we are exposed to significant downside risk related to a change in interest on our money market accounts. The Company did not have any investments in marketable securities at December 31, 2019.

Based on current interest rates, we do not believe we are exposed to significant downside risk related to change in interest on our investment accounts.

The interest rate risk related to borrowings under our line of credit is based on LIBOR plus an interest rate spread. There is no LIBOR minimum and the LIBOR pricing provides for an interest rate spread of 1.75% to 2.75% (representing an interest rate of 4.5% at December 31, 2019). As of December 31, 2019, we had $18.5 million in borrowings outstanding under our revolving line of credit.

Exchange Rate Risk

While we operate primarily in the U.S., we are exposed to foreign currency risk. A portion of our research and development is performed abroad.

Currently, we do not utilize financial instruments to hedge exposure to foreign currency fluctuations. We believe our exposure to foreign currency fluctuation is minimal as our purchases in foreign currency have a maximum exposure of 90 days based on invoice terms with a portion of the exposure being limited to 30 days based on the due date of the invoice. Foreign currency exchange losses were immaterial for 2019, 2018 and 2017. Neither a five percent increase nor decrease from current exchange rates would have had a material effect on our operating results or financial condition.

Item 8. Financial Statements and Supplementary Data.

See consolidated financial statements, including the reports of the independent registered public accounting firm, starting on page F-1, which is incorporated herein by reference.

Item 9. Changes in and Disagreements with Accountants on Accounting and Financial Disclosure.

None.

Item 9A. Controls and Procedures.

Our Chief Executive Officer and Chief Financial Officer have evaluated the effectiveness of the design and operation of our disclosure controls and procedures as of December 31, 2019. Based on that evaluation, they have concluded that our disclosure controls and procedures were effective as of December 31, 2019 to ensure that material information relating to us and our consolidated subsidiaries is made known to officers within these entities in order to allow for timely decisions regarding required disclosure.

Management's report on internal control over financial reporting is included on page F-1 of this annual report on Form 10-K, and incorporated herein by reference. During our fourth quarter of 2019, there were no changes in our internal control over financial reporting (as defined in Rule 13a-15(f) or 15d-15(f)).

Item 9B. Other Information.

Form 8-K, Item 5.02(e). Compensatory Arrangements of Certain Officers

On March 16, 2020, the Company entered into new employment agreements with each of A.J. Kazimi, our Chief Executive Officer (the 'Kazimi Employment Agreement'), Martin Cearnal, our Executive Vice President and Chief Commercial Officer (the 'Cearnal Employment Agreement'), Leo Pavliv, our Executive Vice President, Operations and Chief Development Officer (the 'Pavliv Employment Agreement'), James Herman, our Senior Vice President, National Accounts and Chief Compliance Officer (the 'Herman Employment Agreement,' and Michael Bonner, our Senior Director, Finance and Accounting and Chief Financial Officer (the 'Bonner Employment Agreement'), and together with the Kazimi Employment Agreement, the Cearnal Employment Agreement, the Pavliv Employment Agreement, and the Herman Employment Agreement, the 'Employment Agreements'). The Employment Agreements were effective as of January 1, 2020.

Employment Agreements

Each Employment Agreement provides for a salary for services performed, a potential annual bonus and a grant of restricted common shares pursuant to a restricted stock agreement.Under the terms of each Employment Agreement, employment is at-will and may be terminated by the Company at any time, with or without notice and with or without cause. Similarly, each of Mr. Kazimi, Mr. Cearnal, Mr. Pavliv, Mr. Bonner, and Mr. Herman may terminate his respective employment with us at any time, with or without notice. The Employment Agreements do not provide for any severance payments in the event employment is terminated for cause nor any severance benefits in the event employment is terminated as a result of death or permanent disability. The Employment Agreements include non-competition, non-solicitation and non-disclosure covenants on the part of employees. The Employment Agreements impose obligations regarding confidential information and state that any discoveries or improvements conceived, developed or otherwise made by the employees, or with others, are deemed our sole property. The Employment Agreements do not contain any termination or change in control provisions.

Kazimi Employment Agreement

Pursuant to the Kazimi Employment Agreement, Mr. Kazimi will serve as the Company's Chief Executive Officer and will receive a base salary of $589,500.

The foregoing descriptions of the Kazimi Employment Agreement are qualified in their entirety by reference to the Kazimi Employment Agreement, which is included as Exhibit 10.11 to this Annual Report on Form 10-K and are incorporated by reference into this Item. The foregoing description of the Kazimi Employment Agreement does not purport to be complete and is qualified in its entirety by reference to such exhibit.

Cearnal Employment Agreement

Pursuant to the Cearnal Employment Agreement, Mr. Cearnal will serve as the Company's Executive Vice President and Chief Commercial Officer and will receive a base salary of $325,000.

The foregoing descriptions of the Cearnal Employment Agreement are qualified in their entirety by reference to the Cearnal Employment Agreement, which is included as Exhibit 10.12 to this Annual Report on Form 10-K and are incorporated by reference into this Item. The foregoing description of the Cearnal Employment Agreement does not purport to be complete and is qualified in its entirety by reference to such exhibit.

Pavliv Employment Agreement

Pursuant to the Pavliv Employment Agreement, Mr. Pavliv will serve as the Company's Executive Vice President, Operations and Chief Development Officer and will receive a base salary of $422,000.

The foregoing descriptions of the Pavliv Employment Agreement are qualified in their entirety by reference to the Pavliv Employment Agreement, which is included as Exhibit 10.13 to this Annual Report on Form 10-K and are incorporated by reference into this Item. The foregoing description of the Pavliv Employment Agreement does not purport to be complete and is qualified in its entirety by reference to such exhibit.

Herman Employment Agreement

Pursuant to the Herman Employment Agreement, Mr. Herman will serve as the Company's Senior Vice President, National Accounts and Chief Compliance Officer and will receive a base salary of $260,000.

The foregoing descriptions of the Herman Employment Agreement are qualified in their entirety by reference to the Herman Employment Agreement, which is included as Exhibit 10.15 to this Annual Report on Form 10-K and are incorporated by reference into this Item. The foregoing description of the Herman Employment Agreement does not purport to be complete and is qualified in its entirety by reference to such exhibit.

Bonner Employment Agreement

Pursuant to the Bonner Employment Agreement, Mr. Bonner will serve as the Company's Senior Director, Finance and Accounting and Chief Financial Officer and will receive a base salary of $205,500.

The foregoing descriptions of the Bonner Employment Agreement are qualified in their entirety by reference to the Bonner Employment Agreement, which is included as Exhibit 10.14 to this Annual Report on Form 10-K and are incorporated by reference into this Item. The foregoing description of the Bonner Employment Agreement does not purport to be complete and is qualified in its entirety by reference to such exhibit.

PART III

The information called for by Part III of Form 10-K (Item 10 – Directors, Executive Officers and Corporate Governance, Item 11 – Executive Compensation, Item 12 – Security Ownership of Certain Beneficial Owners and Management and Related Stockholder Matters, Item 13 – Certain Relationships and Related Transactions, and Director Independence, Item 14 – Principal Accounting Fees and Services), is incorporated by reference from our proxy statement related to our 2020 annual meeting of shareholders, which is expected to be filed with the SEC on or around March 20, 2020.

PART IV

Item 15. Exhibits, Financial Statement Schedules.

a.Documents filed as part of this report:

1.Financial Statements

(2) Financial Statement Schedule

b. Exhibits

Exhibit

Number

Descrizione
3.1
3.2
4.1
4.2
4.3
4.4
4.5#
4.6.1#
4.6.2#
4.7#
4.8
4.9
4.10
10.7†
10.7.1†
10.10†
10.11#
10 .12#
10.13#
10.14#
10.15#
10.17#
10.18#
10.19#
10.2
10.21†
10.21.1†
10.21.2†
10.21.3†
10.23†
10.24
10.24.1
10.24.2†
10.25†
10.28†
10.30#
10.31†
10.32†
10.34
10.35
10.36
10.37
# Indicates a management contract or compensatory plan.
Confidential treatment has been granted for portions of this exhibit. These portions have been omitted from the Registration Statement and submitted separately to the Securities and Exchange Commission.
†† Confidential treatment has been requested for portions of this exhibit. These portions have been omitted from the Registration Statement and submitted separately to the Securities and Exchange Commission.

Item 16. Form 10-K Summary

Registrants may voluntarily include a summary of information required by Form 10-K under this Item 16. The Company has elected not to include such summary information.

SIGNATURES

Pursuant to the requirements of Section 13 or 15(d) of the Securities Exchange Act of 1934, the registrant has duly caused this report to be signed on its behalf by the undersigned, thereunto duly authorized, on March 20, 2020.

Cumberland Pharmaceuticals, Inc.
/s/ A. J. Kazimi
By: A. J. Kazimi
Chief Executive Officer
(Principal Executive Officer)

Pursuant to the requirements of the Securities Exchange Act of 1934, this report has been signed below by the following persons on behalf of the registrant and in the capacities and on the dates indicated.

Signature Title Date
/s/ A. J. Kazimi Chairman and CEO 20 marzo 2020
A. J. Kazimi (Principal Executive Officer and Director)
/s/ Michael P. Bonner Senior Director and CFO 20 marzo 2020
Michael P. Bonner

(Principal Financial and

Accounting Officer

/s/ Martin E. Cearnal Director 20 marzo 2020
Martin E. Cearnal
/s/ Gordon R. Bernard Director 20 marzo 2020
Gordon R. Bernard
/s/ Jonathan I. Griggs Director 20 marzo 2020
Jonathan I. Griggs
/s/ James R. Jones Director 20 marzo 2020
James R. Jones
/s/ Joey A. Jacobs Director 20 marzo 2020
Joey A. Jacobs
/s/ Caroline R. Young Director 20 marzo 2020
Caroline R. Young
/s/ Kenneth J. Krogulski Director 20 marzo 2020
Kenneth J. Krogulski
/s/ Joseph C. Galante Director 20 marzo 2020
Joseph C. Galante

MANAGEMENT'S REPORT ON INTERNAL CONTROL OVER FINANCIAL REPORTING

The management of Cumberland Pharmaceuticals Inc. and its subsidiaries (the 'Company') is responsible for establishing and maintaining adequate internal control over financial reporting. Cumberland Pharmaceuticals Inc.'s internal control system was designed to provide reasonable assurance to the Company's management and board of directors regarding the preparation and fair presentation of published financial statements. All internal control systems, no matter how well designed, have inherent limitations. Therefore, even those systems determined to be effective can provide only reasonable assurance with respect to financial statement preparation and presentation.

Cumberland Pharmaceuticals Inc.'s management assessed the effectiveness of the Company's internal control over financial reporting as of December 31, 2019. In making this assessment, it used the criteria set forth by the Committee of Sponsoring Organizations of the Treadway Commission (COSO) in Internal Control – Integrated Framework (2013).

Based on its assessment, management has concluded that, as of December 31, 2019, the Company's internal control over financial reporting was effective based on those criteria.

/s/ A. J. Kazimi
A. J. Kazimi
Chief Executive Officer
20 marzo 2020
/s/ Michael Bonner
Michael Bonner
Chief Financial Officer
20 marzo 2020

Report of Independent Registered Public Accounting Firm

Shareholders and Board of Directors

Cumberland Pharmaceuticals Inc.

Nashville, Tennessee

Opinion on the Consolidated Financial Statements

We have audited the accompanying consolidated balance sheets of Cumberland Pharmaceuticals Inc. (the 'Company') as of December 31, 2019 and 2018, the related consolidated statements of operations and comprehensive income (loss), equity, and cash flows for each of the three years in the period ended December 31, 2019 and the related notes and financial statement schedule listed in the accompanying index (collectively referred to as the 'consolidated financial statements'). In our opinion, the consolidated financial statements present fairly, in all material respects, the financial position of the Company at December 31, 2019 and 2018, and the results of its operations and its cash flows for each of the three years in the period ended December 31, 2019,in conformity with accounting principles generally accepted in the United States of America.

Basis for Opinion

These consolidated financial statements are the responsibility of the Company's management. Our responsibility is to express an opinion on the Company's consolidated financial statements based on our audits. We are a public accounting firm registered with the Public Company Accounting Oversight Board (United States) ('PCAOB') and are required to be independent with respect to the Company in accordance with the U.S. federal securities laws and the applicable rules and regulations of the Securities and Exchange Commission and the PCAOB.

We conducted our audits in accordance with the standards of the PCAOB. Those standards require that we plan and perform the audit to obtain reasonable assurance about whether the consolidated financial statements are free of material misstatement, whether due to error or fraud. The Company is not required to have, nor were we engaged to perform, an audit of its internal control over financial reporting. As part of our audits we are required to obtain an understanding of internal control over financial reporting but not for the purpose of expressing an opinion on the effectiveness of the Company's internal control over financial reporting. Accordingly, we express no such opinion.

Our audits included performing procedures to assess the risks of material misstatement of the consolidated financial statements, whether due to error or fraud, and performing procedures that respond to those risks. Such procedures included examining, on a test basis, evidence regarding the amounts and disclosures in the consolidated financial statements. Our audits also included evaluating the accounting principles used and significant estimates made by management, as well as evaluating the overall presentation of the consolidated financial statements. We believe that our audits provide a reasonable basis for our opinion.

/s/ BDO USA, LLP

We have served as the Company's auditor since 2017.

Nashville, Tennessee

20 marzo 2020

CUMBERLAND PHARMACEUTICALS INC. AND SUBSIDIARIES

Consolidated Balance Sheets

December 31, 2019 and 2018

2019 2018
ASSETS
Current assets:
Cash and cash equivalents $ 28,212,635 $ 27,938,960
Marketable securities 8,290,679
Accounts receivable, net 9,781,463 7,844,249
Inventories, net 9,411,521 12,078,343
Prepaid and other current assets 2,757,456 2,963,806
Total current assets 50,163,075 59,116,037
Non-current inventories 15,554,992 15,749,000
Property and equipment, net 747,796 771,213
Intangible assets, net 30,920,324 33,655,099
Goodwill 882,000 784,000
Deferred tax assets, net 21,802 87,210
Operating lease right-of-use assets 2,960,569
Other assets 3,298,725 2,531,309
Total assets $ 104,549,283 $ 112,693,868
LIABILITIES AND EQUITY
Current liabilities:
Accounts payable $ 11,912,446 $ 11,093,297
Operating lease current liabilities 920,431
Other current liabilities 11,317,358 16,710,927
Total current liabilities 24,150,235 27,804,224
Revolving line of credit 18,500,000 20,000,000
Operating lease noncurrent liabilities 2,076,472
Other long-term liabilities 8,737,323 9,319,143
Total liabilities 53,464,030 57,123,367
Commitments and contingencies
Equity:
Shareholders' equity:
Common stock – no par value; 100,000,000 shares authorized; 15,263,555 and 15,481,497 shares issued and outstanding as of December 31, 2019 and 2018, respectively 49,914,478 51,098,613
Retained earnings 1,208,395 4,746,154
Total shareholders' equity 51,122,873 55,844,767
Noncontrolling interests (37,620) (274,266)
Total equity 51,085,253 55,570,501
Total liabilities and equity $ 104,549,283 $ 112,693,868

See accompanying notes to consolidated financial statements.

CUMBERLAND PHARMACEUTICALS INC. AND SUBSIDIARIES

Consolidated Statements of Operations and Comprehensive Income (Loss)

Years ended December 31, 2019, 2018 and 2017

2019 2018 2017
Revenues:
Net product revenue $ 45,552,587 $ 40,200,832 $ 40,376,563
Other revenue 1,981,050 540,933 773,568
Net revenues 47,533,637 40,741,765 41,150,131
Costs and expenses:
Cost of products sold 8,752,020 7,378,095 7,370,585
Selling and marketing 21,429,040 20,258,307 21,492,937
Research and development 6,478,592 7,575,892 4,280,385
General and administrative 10,362,433 10,150,777 9,651,350
Amortization 4,134,557 2,769,466 2,436,222
Total costs and expenses 51,156,642 48,132,537 45,231,479
Operating income (loss) (3,623,005) (7,390,772) (4,081,348)
Interest income 243,364 564,484 299,326
Interest expense (246,186) (195,848) (92,904)
Income (loss) before income taxes (3,625,827) (7,022,136) (3,874,926)
Income tax (expense) benefit 79,316 (16,636) (4,174,889)
Net income (loss) (3,546,511) (7,038,772) (8,049,815)
Net loss at subsidiary attributable to noncontrolling interests 8,752 75,704 71,182
Net income (loss) attributable to common shareholders $ (3,537,759) $ (6,963,068) $ (7,978,633)
Earnings (loss) per share attributable to common shareholders:
Basic $ (0.23) $ (0.45) $ (0.50)
Diluted $ (0.23) $ (0.45) $ (0.50)
Weighted-average common shares outstanding:
Basic 15,396,098 15,614,052 15,911,577
Diluted 15,396,098 15,614,052 15,911,577
Comprehensive income (loss) attributable to common shareholders $ (3,537,759) $ (6,963,068) $ (7,978,633)
Net loss at subsidiary attributable to noncontrolling interests 8,752 75,704 71,182
Total comprehensive income (loss) $ (3,546,511) $ (7,038,772) $ (8,049,815)

See accompanying notes to consolidated financial statements.

CUMBERLAND PHARMACEUTICALS INC. AND SUBSIDIARIES

Consolidated Statements of Cash Flows

Years ended December 31, 2019, 2018 and 2017

2019 2018 2017
Cash flows from operating activities:
Net income (loss) $ (3,546,511) $ (7,038,772) $ (8,049,815)
Adjustments to reconcile net income (loss) to net cash flows provided by (used in) operating activities:
Depreciation and amortization expense 4,404,175 2,982,703 2,647,753
Deferred tax expense 65,408 81,886 4,206,753
Share-based compensation 1,485,898 1,364,698 1,115,063
Share-based compensation (foundation contribution) 372,500
Excess tax (benefit) expense derived from exercise of stock options (81,886) (91,109)
Decrease in non-cash contingent consideration (804,167)
Noncash interest expense 47,525 99,883 77,911
Noncash investment gains (26,315) (168,440) (52,012)
Net changes in assets and liabilities affecting operating activities:
Accounts receivable (1,937,214) 550,863 (1,064,985)
Inventories 2,860,830 460,505 (1,366,118)
Other current assets and other assets (587,477) 712,149 (1,074,369)
Accounts payable and other current liabilities 1,824,024 4,308,706 2,307,617
Other long-term liabilities (729,820) (159,558) 413,097
Net cash provided by (used in) operating activities 3,056,356 3,112,737 (557,714)
Cash flows from investing activities:
Additions to property and equipment (246,202) (455,569) (275,960)
Additions to intangible assets (772,944) (3,819,486) (1,213,110)
Cash paid for acquisition (5,000,000) (20,000,000)
Proceeds from sale of marketable securities 20,062,132 16,122,376 13,381,061
Purchases of marketable securities (11,745,138) (19,572,139) (2,379,414)
Net cash provided by (used in) investing activities 2,297,848 (27,724,818) 9,512,577
Cash flows from financing activities:
Borrowings on line of credit 76,000,000 56,000,000 24,500,000
Repayments on line of credit (77,500,000) (45,800,000) (18,800,000)
Repurchase of common shares (3,494,921) (2,879,426) (3,724,375)
Payments of deferred equity offering costs (383,310) (27,950)
Sales of shares of common stock, net of offering costs 200,909
Payments of financing costs (52,500)
Cash payments of contingent consideration (1,033,108)
Sale of subsidiary shares to noncontrolling interest 1,000,000
Net cash provided by (used in) financing activities (5,080,529) 7,138,173 1,947,675
Net increase (decrease) in cash and cash equivalents 273,675 (17,473,908) 10,902,538
Cash and cash equivalents, beginning of year 27,938,960 45,412,868 34,510,330
Cash and cash equivalents, end of year $ 28,212,635 $ 27,938,960 $ 45,412,868
Supplemental disclosure of cash flow information:
Net cash paid (refunded) during the year for:
Interest $ 198,661 $ 95,965 $ 14,993
Income taxes 16,694 15,441 18,000
Noncash investing and financing activities:
Change in unpaid invoices for purchases of intangibles $ (576,837) $ (539,467) $ (513,481)
Deferred offering costs included in accounts payable and other accrued expenses 97,254
Non cash increase in liabilities related to acquisition (see Note 3) 14,034,000
Recognition of operating lease assets and liabilities through adoption of ASC 842 3,629,320
Vesting of shares related to RediTrex approval 862,200
Repurchase of subsidiary shares from noncontrolling interests (800,000)
Additions to intangible assets from final purchase price allocation 148,000

See accompanying notes to consolidated financial statements

CUMBERLAND PHARMACEUTICALS INC. AND SUBSIDIARIES

Consolidated Statements of Equity

Years ended December 31, 2019, 2018 and 2017

Cumberland Pharmaceuticals Inc. Shareholders
Common stock Retained earnings Non-controlling interest Total equity
Shares Amount
Balance, December 31, 2016 16,074,176 $ 54,643,268 $ 18,604,931 $ (127,380) $ 73,120,819
Net income (loss) (7,978,633) (71,182) (8,049,815)
Cumulative effect from change in accounting principle 1,082,924 1,082,924
Share-based compensation 146,275 1,115,063 1,115,063
Exercise of options and related tax benefit 50,000 372,500 372,500
Repurchase of common shares (547,376) (3,719,890) (3,719,890)
Balance, December 31, 2017 15,723,075 52,410,941 11,709,222 (198,562) 63,921,601
Net income (loss) (6,963,068) (75,704) (7,038,772)
Share-based compensation 170,759 1,364,698 1,364,698
Proceeds from sale of common stock, net of offering costs 30,704 200,909 200,909
Repurchase of common shares (443,041) (2,877,935) (2,877,935)
Balance, December 31, 2018 15,481,497 51,098,613 4,746,154 (274,266) 55,570,501
Net income (loss) (3,537,759) (8,752) (3,546,511)
Repurchase of subsidiary shares to noncontrolling interest (685,805) (114,195) (800,000)
Sale of subsidiary shares to noncontrolling interest 640,407 359,593 1,000,000
Vesting of common stock 180,000 862,200 862,200
Share-based compensation 225,536 1,485,898 1,485,898
Repurchase of common shares (623,478) (3,486,835) (3,486,835)
Balance, December 31, 2019 15,263,555 $ 49,914,478 $ 1,208,395 $ (37,620) $ 51,085,253

See accompanying notes to consolidated financial statements

CUMBERLAND PHARMACEUTICALS INC. AND SUBSIDIARIES

Notes to Consolidated Financial Statements

(1) Organization

Cumberland Pharmaceuticals Inc. ('Cumberland,' the 'Company,' or as used in the context of 'we,' 'us,' or 'our') is a specialty pharmaceutical company focused on the acquisition, development and commercialization of branded prescription products. The Company's primary target markets are hospital acute care and gastroenterology. These medical specialties are characterized by relatively concentrated prescriber bases that the Company believes can be penetrated effectively by small, targeted sales forces. Cumberland is dedicated to providing innovative products that improve quality of care for patients and address unmet or poorly met medical needs. The Company promotes its approved products through its hospital and field sales forces in the United States and is establishing a network of international partners to bring its medicines to patients in their countries.

Cumberland focuses its resources on maximizing the commercial potential of its products, as well as developing new product candidates, and has both internal development and commercial capabilities. The Company's products are manufactured by third parties, which are overseen by Cumberland's quality and manufacturing professionals. The Company works closely with its third-party distribution partners to make its products available in the United States.

In order to build a pipeline of early-stage product candidates, the Company formed a subsidiary, Cumberland Emerging Technologies, Inc. ('CET'), which teams with universities and other research organizations to help advance scientific discoveries from the laboratory to the marketplace. In 2014, the Company organized equity financing to recapitalize and strengthen the financial position of CET including an investment of approximately $1.0 million from Gloria Pharmaceuticals Co., Ltd. ('Gloria'). As a result, Gloria received shares in CET and joined the CET ownership group.

In April, 2019, CET entered into an agreement with HongKong WinHealth Pharma Group Co. Limited (WinHealth) whereby WinHealth made a$1.0 million investment through the purchase of shares of CET stock. As part of the agreement, WinHealth obtained a Board position at CET and the first opportunity to license CET products for the Chinese market. In connection with WinHealth's investment in CET, Cumberland also made an additional $1.0 million investment in CET. Cumberland purchased additional CET shares through contribution of $0.3 million in cash and a conversion of $0.7 million in intercompany loans payable. Upon completion of the additional investment by WinHealth and Cumberland, Gloria Pharmaceuticals agreed to return its shares in CET in exchange for consideration of $0.8 million.

The Company's ownership in CET is now 85%. As noted above, the ownership interests of CET includes WinHealth and Cumberland, while the remaining interest is owned by Vanderbilt University and the Tennessee Technology Development Corporation. The operating results of CET allocated to noncontrolling interests in the consolidated statements of operations were $8,752, $75,704 and $71,182 for the years ended December 31, 2019, 2018 and 2017, respectively.

Effective January 1, 2007, the Company formed a wholly-owned subsidiary, Cumberland Pharma Sales Corp. ('CPSC'). CPSC is the subsidiary that employs the Company's hospital and field sales force personnel.

(2) Significant Accounting Policies

Principles of Consolidation

The consolidated financial statements of the Company are stated in U.S. dollars and are prepared using U.S. generally accepted accounting principles. These financial statements include the accounts of the Company and its

CUMBERLAND PHARMACEUTICALS INC. AND SUBSIDIARIES

Notes to Consolidated Financial Statements (Continued)

wholly and majority-owned subsidiaries. All significant intercompany transactions and accounts have been eliminated in consolidation.

Use of Estimates

The preparation of the consolidated financial statements in conformity with U.S. generally accepted accounting principles requires management of the Company to make estimates and assumptions that affect the reported amounts of assets and liabilities and disclosure of contingent liabilities at the date of the consolidated financial statements and the reported amounts of revenues and expenses during the period. Actual results could differ from those estimates under different assumptions and conditions. The Company's most significant estimates include: (1) its allowances for chargebacks and accruals for rebates and product returns (2) the allowances for obsolescent or unmarketable inventory (3) assumptions used in estimating acquisition date fair value of assets acquired in business combinations and (4) valuation of contingent consideration liability associated with business combinations.

Segment Reporting

The Company has one operating segment which is specialty pharmaceutical products. Management has chosen to organize the Company based on the type of products sold. Operating segments are identified as components of an enterprise about which separate discrete financial information is evaluated by the chief operating decision maker, or decision-making group, in making decisions regarding resource allocation and assessing performance. The Company, which uses consolidated financial information in determining how to allocate resources and assess performance, evaluated that our specialty pharmaceutical products compete in similar economic markets and similar circumstances. Substantially all of the Company's assets are located in the United States. Total revenues are primarily attributable to U.S. customers. Net revenues from customers outside the United States were approximately $1.5 million, $2.1 million and $1.6 million for the years ended December 31, 2019, 2018 and 2017, respectively.

Fair Value of Financial Instruments

Fair value of financial assets and liabilities is the price the Company would receive to sell an asset or pay to transfer a liability in an orderly transaction with a market participant at the measurement date. The Company's fair value measurements follow the appropriate rules as well as the fair value hierarchy that prioritizes the information used to develop the measurements. It applies whenever other guidance requires (or permits) assets or liabilities to be measured at fair value and gives the highest priority to unadjusted quoted prices in active markets for identical assets or liabilities (Level 1 measurements) and the lowest priority to unobservable inputs (Level 3 measurements).

A summary of the fair value hierarchy that prioritizes observable and unobservable inputs used to measure fair value into three broad levels is described below:

Level 1 – Quoted prices for identical instruments in active markets.

Level 2 – Quoted prices for similar instruments in active markets; quoted prices for identical or similar instruments in markets that are not active; and model-derived valuations whose inputs are observable or whose significant value drivers are observable.

Level 3 – Significant inputs to the valuation model are unobservable.

We maintain policies and procedures to value instruments using the best and most relevant data available. The following section describes the valuation methodologies we use to measure different financial instruments at fair value on a recurring basis.

The Company's financial instruments include cash and cash equivalents, marketable securities, accounts receivable, accounts payable, accrued liabilities, contingent consideration liability and a revolving line of credit. The carrying values for cash and cash equivalents, accounts receivable, accounts payable and accrued liabilities approximate their fair values due to their short-term nature. The revolving line of credit has a variable interest rate, which approximates the current market rate.

CUMBERLAND PHARMACEUTICALS INC. AND SUBSIDIARIES

Notes to Consolidated Financial Statements (Continued)

The Company's fair values of marketable securities are determined based on valuations provided by a third-party pricing service, as derived from such services' pricing models, and are considered either Level 1 or Level 2 measurements, depending on the nature of the investment. The Company has no marketable securities in which the fair value is determined based on Level 3. The level of management judgment required in evaluating fair value for Level 1 investments is minimal. Similarly, there is little subjectivity or judgment required for Level 2 investments valued using valuation models that are standard across the industry and whose parameter inputs are quoted in active markets. Inputs to the models may include, but are not limited to, reported trades, executable bid and ask prices, broker/dealer quotations, prices or yields of securities with similar characteristics, benchmark curves or information pertaining to the issuer, as well as industry and economic events. The Company believes that the valuations provided by the third-party pricing service, as derived from such services' pricing models, represent prices that would be received to sell the assets at the measurement date (exit prices).

The Company's contingent consideration liability is a Level 3 fair value measurement that is updated on a recurring basis at each reporting period using a valuation model. Consistent with Level 3 fair value measurements, there are significant inputs to the valuation model that are unobservable.

Cash and Cash Equivalents

Cash and cash equivalents include highly liquid investments with original maturities of three months or less. As of December 31, 2019 and 2018, cash equivalents consist primarily of money market funds as well as trading securities with original maturities of less than ninety days.

Marketable Securities

The Company invests in marketable debt securities in order to maximize its return on cash. Marketable securities consist of short-term cash investments, U.S. Treasury notes and bonds, corporate bonds, and commercial paper. At the time of purchase, the Company classifies marketable securities as either trading securities or available-for-sale securities, depending on the intent at that time. As of December 31, 2019 and 2018, marketable securities were comprised solely of trading securities. Trading securities are carried at fair value with unrealized gains and losses recognized as a component of interest income in the consolidated statements of operations. As of December 31, 2019, all the trading securities were commercial paper with original maturities of less than ninety days and as a result, were classified as cash equivalents.

Accounts Receivable

Trade accounts receivable are recorded at the invoiced amount. The Company records allowances for amounts that could become uncollectible in the future based on historical experience, including amounts related to chargebacks, cash discounts and credits for damaged product. The Company reviews each customer balance to assess collection status.

The majority of the Company's products are distributed through independent pharmaceutical wholesalers. The allowances against accounts receivable for chargebacks and discounts are determined on a product-by-product basis, and established by management as the Company's best estimate at the time of sale based on each product's historical experience adjusted to reflect known changes in the factors that impact such allowances. These allowances are established based on the contractual terms with direct and indirect customers and analyses of historical levels of chargebacks, discounts and credits claimed for damaged and expired product. The allowances in accounts receivable for chargebacks, cash discounts and damaged goods were $0.8 million at December 31, 2019 and $0.9 million at December 31, 2018.

Other organizations, such as managed care providers, pharmacy benefit management companies and government agencies, may receive rebates from the Company based on either negotiated contracts to carry the Company's products or reimbursements for filled prescriptions. These entities are considered indirect customers of

CUMBERLAND PHARMACEUTICALS INC. AND SUBSIDIARIES

Notes to Consolidated Financial Statements (Continued)

the Company. In conjunction with recognizing a sale to a wholesaler, revenues are reduced and accrued liabilities are increased by the Company's estimate of the rebate that may be claimed as well as the reserves for expired and damaged goods.

Cash discounts are reductions to invoiced amounts offered to customers for payment within a specified period of time from the date of the invoice.

Inventories

The Company works closely with third parties to manufacture and package finished goods for sale. Based on the customer relationship with the manufacturer or packager, the Company will either take title to finished goods at the time of shipment or at the time of arrival from the manufacturer. The Company then warehouses such goods until distribution and sale. As discussed below, effective January 1, 2017, inventories are stated at the lower of cost or net realizable value with cost determined using the first-in, first-out method.

The Company continually evaluates inventories for potential losses due to expired, short-dated or slow-moving inventory by comparing sales history and sales projections to the inventory on hand. When evidence indicates the carrying value of a product may not be recoverable, a charge is recorded to reduce the inventory to its current net realizable value. The Company classifies the Vibativ inventories that it does not expect to sell within one year as non-current inventories.

Prepaid and Other Current Assets

Prepaid and other current assets consist of deferred offering costs, prepaid insurance premiums, prepaid consulting services, deposits and annual fees paid to the U.S. Food and Drug Administration ('FDA'). The Company expenses all prepaid and other current asset amounts as used or over the period of benefit primarily on a straight-line basis, as applicable.

Deferred offering costs are expenses directly related to the Form S-3 or Shelf Registration filed with the SEC on November 11, 2017 and declared effective on January 16, 2018. These costs consist of legal, accounting, printing, and filing fees that the Company has capitalized. Deferred costs associated with the Shelf Registration will be reclassified to additional paid in capital on a pro-rata basis as the Company completes sales of shares under the Shelf Registration, with any remaining deferred offering costs to be charged to the results of operations at the end of the three-year life of the Shelf Registration. During the year ended December 31, 2019, the Company has not expensed any deferred offering costs associated with the Shelf Registration.

Property and Equipment

Property and equipment, including leasehold improvements, are stated at cost. Depreciation is recognized using the straight-line method over the estimated useful lives of the assets. Leasehold improvements are amortized over the shorter of the initial lease term plus renewal options, if reasonably assured, or the remaining useful life of the asset. Upon retirement or disposal of assets, any gain or loss is reflected as a component of operating income (loss) in the consolidated statement of operations. Improvements that extend an asset's useful life are capitalized. Repairs and maintenance costs are expensed as incurred.

Intangible Assets and Goodwill

The Company's intangible assets and goodwill consist of capitalized costs related to product and license rights, patents, trademarks and goodwill obtained in the Vibativ acquisition. Goodwill is not amortized for financial reporting purposes, but is subject to impairment analysis at least annually.

The cost of acquiring product and license rights are capitalized at fair value at the date of acquisition for products that are approved by the FDA for commercial use. These costs are amortized ratably over the estimated economic life of the product. The economic life is estimated based upon several factors. This includes the term of the license agreement, the patent life or market exclusivity of the product and as well as management's expectations

CUMBERLAND PHARMACEUTICALS INC. AND SUBSIDIARIES

Notes to Consolidated Financial Statements (Continued)

of continued involvement with the product and the assessment of future sales, the future periods under which the product will be sold and the profitability of the product. This estimate is evaluated on a regular basis during the amortization period and adjusted if appropriate. If there are any changes made to the useful life of the product and license rights, the costs associated with such a change, if any, will be capitalized and amortized over the revised useful life.

Capitalized patent costs consist of outside legal costs associated with obtaining and protecting patents on products that have been approved for marketing by the FDA. If it becomes probable that a patent will not be issued or a patent has been declared invalid, related costs associated with the patent application are expensed at the time such determination is made. All costs associated with obtaining patents for products that have not been approved for marketing by the FDA are expensed as incurred.

Amortization expense is recognized ratably over the following periods:

Product rights Estimated economic life
License rights Term of license agreement
Patents Life of patent

Impairment of Long-Lived Assets

Long-lived assets, such as property and equipment, operating lease right-of-use assets and intangible assets subject to amortization, are reviewed for impairment whenever events or changes in circumstances indicate the carrying amount of an asset may not be recoverable. If events or circumstances arise that require a long-lived asset to be tested for potential impairment, the Company first compares undiscounted cash flows expected to be generated by the asset to its carrying value. If the carrying amount of the long-lived asset is not recoverable on an undiscounted cash flow basis, an impairment charge is recognized to the extent that the carrying value exceeds the fair value. Fair value is determined through various valuation techniques including quoted market prices, third-party independent appraisals and discounted cash flow models.

Goodwill and other indefinite lived intangible assets that are not subject to amortization are tested at least annually for impairment. The impairment analysis for goodwill requires a comparison of fair value to the carrying value of the reporting unit. The Company's goodwill was acquired in November 2018 with the Vibativ acquisition. As a result, the Vibativ component of the Company is the reporting unit evaluated for goodwill impairment. Cumberland determined the fair value of the reporting unit through current and future estimated revenue and profitability of the product. The Company recorded no impairment charges during 2019, 2018 and 2017.

Revenue Recognition

Effective January 1, 2018, the Company adopted the Financial Accounting Standards Board's ('FASB') amended guidance in the form of Accounting Standards Update ('ASU') No. 2014-09, 'Revenue from Contracts with Customers,' (ASC 606). Results for reporting periods beginning after January 1, 2018 are presented under ASC 606, while prior period amounts were not adjusted and are reported in accordance with ASC 605.

Net Product Revenue

Revenues from product sales are recognized in the amount that reflects the consideration that we expect to receive for these goods. Depending upon the shipping terms of the transaction, the revenue is recognized.at the point where the customer obtains control of the goods and we satisfy our performance obligation. This occurs upon either shipment of the product or arrival at its ship to destination. Payment terms typically range from 30 to 60 days from date of shipment. The Company's net product revenue reflects the reduction from gross product revenue for estimated allowances for chargebacks, discounts and damaged goods, and reflects sales related accruals for rebates, coupons, product returns, and certain administrative and service fees. Significant judgments must be made in determining the transaction price for our sales of products related to these adjustments.

CUMBERLAND PHARMACEUTICALS INC. AND SUBSIDIARIES

Notes to Consolidated Financial Statements (Continued)

Sales Rebates and Discounts

The allowances against accounts receivable for chargebacks, discounts, expired and damaged goods are determined on a product-by-product basis, and established by management as the Company's best estimate at the time of sale based on each product's historical experience adjusted to reflect known changes in the factors that impact such allowances. These allowances are established based on the contractual terms with direct and indirect customers and analyses of historical levels of chargebacks, discounts and credits claimed for damaged and expired product.

Other organizations, such as managed care providers, pharmacy benefit management companies and government agencies, may receive rebates from the Company based on either negotiated contracts to carry the Company's products or reimbursements for filled prescriptions. These entities are considered indirect customers of the Company. In conjunction with recognizing a sale to a wholesaler, sales revenues are reduced and accrued liabilities are increased by the Company's estimate of the rebate that may be claimed.

Sales Returns

Consistent with industry practice, the Company maintains a return policy that allows customers to return product within a specified period prior to and subsequent to the expiration date. The Company's estimate of the provision for returns is based upon historical experience, expiration date by product as well as any other factor expected to impact future returns. Any changes in the assumptions used to estimate the provision for returns are recognized in the period those assumptions are changed.

Other Revenues

Other revenues primarily consist of income from grant funding programs, licensing agreements, leases and contract services. Revenue related to grants is recognized when all conditions related to such grants have been met. All other revenue is recognized when earned.

Cost of Products Sold

Cost of products sold consists principally of the cost to acquire each unit of product sold, including in-bound freight expense as well as any adjustment in the net realizable value of inventory acquired in acquisitions. Cost of products sold also includes expenses associated with the reduction in the net realizable value of slow-moving or expired product.

Selling and Marketing Expense

Selling and marketing expense consists primarily of expenses relating to the advertising, promotion, distribution and sale of products, including royalty expense, salaries and related costs.

Distribution Costs

Distribution costs are expensed as incurred and are included as a component of selling and marketing expenses in the consolidated statements of operations. Distribution costs were as follows for the years ended December 31:

2019 2018 2017
Distribution costs $ 794,317 $ 618,756 $ 621,142

CUMBERLAND PHARMACEUTICALS INC. AND SUBSIDIARIES

Notes to Consolidated Financial Statements (Continued)

Advertising Costs

Advertising costs are expensed as incurred and are included as a component of selling and marketing expenses in the consolidated statements of operations. Advertising costs were as follows for the years ended December 31:

2019 2018 2017
Advertising costs $ 2,690,280 $ 2,219,074 $ 2,589,185

Research and Development

Research and development costs are expensed in the period incurred. Research and development costs are comprised mainly of clinical trial expenses, salaries, wages and other related costs such as materials and supplies. Research and development expense includes activities performed by third-party providers participating in the Company's clinical studies. The Company accounts for these costs based on estimates of work performed, patients enrolled or fixed fees for services over the period of time the clinical trials are performed.

Income Taxes

The Company provides for deferred taxes using the asset and liability approach. Under this method, deferred tax assets and liabilities are recognized for future tax consequences attributable to operating loss and tax credit carryforwards, as well as differences between the carrying amounts of existing assets and liabilities and their respective tax bases. The Company's principal differences are related to the timing of deductibility of certain items, such as inventory, depreciation, amortization and share-based compensation. Deferred tax assets and liabilities are measured using enacted statutory tax rates that are expected to apply to taxable income in the years such temporary differences are anticipated to be recovered or settled. The effect on deferred tax assets and liabilities of a change in tax rates is recognized in income in the period of enactment. The Company only recognizes income tax benefits associated with an income tax position in which it is 'more likely than not' that the position would be sustained upon examination by the taxing authorities.

In assessing the realizability of deferred tax assets, management considers whether some portion or all of the deferred tax assets will not be realized. The ultimate realization of deferred tax assets is dependent upon the generation of future taxable income during the periods in which those temporary differences become deductible. Management considers the scheduled reversal of existing temporary differences, projected future taxable income and tax planning strategies in making this assessment.

The Company's accounting policy with respect to interest and penalties arising from income tax settlements is to recognize them as part of the provision for income taxes.

Comprehensive Income (Loss)

Total comprehensive income (loss) was comprised solely of net income (loss) for all periods presented.

Earnings (Loss) per Share

Basic earnings (loss) per share is calculated by dividing net income (loss) attributable to common shareholders by the weighted-average number of shares outstanding. Except where the result would be antidilutive to income from continuing operations, diluted earnings (loss) per share is calculated by assuming the vesting of unvested restricted stock and the exercise of stock options and warrants and unrecognized compensation costs.

CUMBERLAND PHARMACEUTICALS INC. AND SUBSIDIARIES

Notes to Consolidated Financial Statements (Continued)

Share-Based Payments

The Company recognizes compensation cost for all share-based payments issued, modified, repurchased or canceled. Depending on the nature of the vesting provisions, restricted stock awards are measured using either the fair value on the grant date or the fair value of common stock on the date the vesting provisions lapse. Prior to the lapse for those equity grants not valued on the grant date, the fair value is measured on the last day of the reporting period.

Collaborative Agreements

The Company is a party to several collaborative arrangements with certain research institutions to identify and pursue promising preclinical pharmaceutical product candidates. The Company has determined these collaborative agreements do not meet the criteria for accounting under Accounting Standards Codification 808, Collaborative Agreements. The agreements do not specifically designate each party's rights and obligations to each other under the collaborative arrangements. Except for patent defense costs, expenses incurred by one party are not required to be reimbursed by the other party. The funding for these programs is generally provided through private sector investments or federal Small Business Administration ('SBIR/STTR') grant programs. Expenses incurred under these collaborative agreements are included in research and development expenses in the consolidated statements of operations. Funding received from private sector investments and grants are recorded as net revenues in the consolidated statements of operations.

Reclassification of prior period amounts

The Company has made certain reclassifications to prior period amounts to conform to the current-year presentation of the reporting of research and development expense and general and administrative expense on the consolidated statements of operations. Certain costs and expenses related to research and development were previously reported as general and administrative expenses on the consolidated statements of operations. These reclassifications have no effect on the reported operating loss or equity for the years ended December 31, 2018 and 2017.

Recent Accounting Guidance

Recent Adopted Accounting Pronouncements

In May 2014, the FASB issued amended guidance in the form of ASU No. 2014-09, 'Revenue from Contracts with Customers' ('ASC 606'). The core principle of the new guidance is to recognize revenues when promised goods or services are transferred to customers in an amount that reflects the consideration to which an entity expects to be entitled for those goods or services. The new guidance defines a five-step process to achieve this core principle and, in doing so, additional judgments and estimates may be required within the revenue recognition process. The new standard replaced most of the existing revenue recognition standards in U.S. GAAP when it became effective. In July 2015, the FASB issued a one-year deferral of the adoption date, which extended the effective date for us to January 1, 2018, at which point Cumberland adopted the standard.

The Company evaluated its revenues and the new guidance had immaterial impacts to recognition practices upon adoption on January 1, 2018. As part of the adoption, the Company elected to apply the new guidance on a modified retrospective basis. The Company did not record a cumulative effect adjustment to historical retained earnings for initially applying the new guidance as no revenue recognition differences were identified in the timing or amount of revenue.

In February 2016, the Financial Accounting Standards Board ('FASB') issued guidance in the form of a FASB Accounting Standards Update ('ASU') No. 2016-02, 'Leases.' The new standard establishes a right-of-use ('ROU') model that requires a lessee to record an ROU asset and a lease liability on the balance sheet for all leases with terms longer than twelve months. Leases will be classified as either finance (formerly 'capital leases') or

CUMBERLAND PHARMACEUTICALS INC. AND SUBSIDIARIES

Notes to Consolidated Financial Statements (Continued)

operating, with classification affecting the pattern of expense recognition in the income statement. The standard provides for a modified retrospective transition approach for lessees for capital and operating leases existing at, or entered into after, the beginning of the earliest comparative period presented in the financial statements, with certain optional practical expedients. In July 2018, the FASB issued ASU 2018-11, 'Leases: Targeted Improvements', allowing for an alternative transition method (the effective date approach). It allows an entity to initially apply the new lease guidance at the adoption date (rather than at the beginning of the earliest period presented). Cumberland adopted the lease guidance effective January 1, 2019 using the package of transition practical expedients. This allowed the Company to retain the lease classification for any leases existing prior to adoption, in addition to other benefits. See additional discussion of the impact of adopting the lease accounting guidance in Note 15.

Recent Accounting Pronouncements – Not Yet Adopted

In June 2016, the FASB issued ASU No. 2016-13, 'Financial Instruments-Credit Losses,' which changes the impairment model for most financial assets and certain other instruments. For trade and other receivables, held-to-maturity debt securities, loans and other instruments, companies will be required to use a new forward-looking 'expected loss' model that generally will result in the earlier recognition of allowances for losses. For available-for-sale debt securities with unrealized losses, companies will measure credit losses in a manner similar to what they do today, except that the losses will be recognized as allowances rather than as reductions in the amortized cost of the securities. Companies will have to disclose more information, including the information they use to track credit quality by year of origination for most financing receivables. Companies will apply the standard's provisions as a cumulative-effect adjustment to retained earnings as of the beginning of the first reporting period in which the guidance is adopted. This standard is effective for the Company on January 1, 2020. The Company continues to evaluate this new standard on its trade and other receivables but does not expect a material impact on its consolidated financial statements.

In May 2019, the FASB issued ASU 2019-05, 'Financial Instruments-Credit Losses (Topic 326): Targeted Transition Relief' which provides transition relief for ASU 2016-13 by providing entities with an alternative to irrevocably elect the fair value option for eligible financial assets measured at amortized cost upon adoption of the new credit losses standard. Certain eligibility requirements must be met, the election must be applied on an instrument-by-instrument basis, and the election is not available for either available-for-sale or held-to-maturity debt securities. The effective date is the same as ASU 2016-13, January 1, 2020. The Company continues to evaluate this new standard but does not expect a material impact on its consolidated financial statements.

In November 2018, the FASB issued ASU No. 2018-18, 'Collaboration Arrangements: Clarifying the Interaction between Topic 808 and Topic 606' (ASU 2018-18). The issuance of ASU 2014-09 raised questions about the interaction between the guidance on collaborative arrangements and revenue recognition. ASU 2018-18 addresses this uncertainty by (1) clarifying that certain transactions between collaborative arrangement participants should be accounted for as revenue under ASU 2014-09 when the collaboration arrangement participant is a customer, (2) adding unit of account guidance to assess whether the collaboration arrangement or a part of the arrangement is with a customer and (3) precluding a company from presenting transactions with collaboration arrangement participants that are not directly related to sales to third parties together with revenue from contracts with customers. The new standard will be effective for the Company on January 1, 2020. The Company continues to evaluate this new standard but does not expect a material impact on its consolidated financial statements.

In January 2017, the FASB issued ASU No. 2017-04, 'Simplifying the Test for Goodwill Impairment' (ASU 2017-04). The guidance removes Step 2 of the goodwill impairment test, which requires a hypothetical purchase price allocation. As a result of the revised guidance, a goodwill impairment will be the amount by which a reporting unit's carrying value exceeds its fair value, not to exceed the carrying amount of goodwill. The new standard will be effective for the Company on January 1, 2020. The Company continues to evaluate this new standard but does not expect a material impact on its consolidated financial statements and related disclosures.

CUMBERLAND PHARMACEUTICALS INC. AND SUBSIDIARIES

Notes to Consolidated Financial Statements (Continued)

(3) Omeclamox®-Pak, RediTrex®and Vibativ®

Omeclamox-Pak

In December 2018, Cumberland completed an agreement with Gasto-enterlogics Inc. ('GEL') to acquire the remaining product rights associated with Omeclamox-Pak including the product's FDA-approved New Drug Application and the domestic and international trademarks. As part of the transaction, which was accounted for as an asset acquisition, Cumberland paid $2.3 million during 2018 and ended Cumberland's payments of royalties and manufacturing fees to GEL. The Company has now assumed responsibility for the maintenance of the product's FDA approval and for the oversight of the product's manufacturing and packaging.

This agreement follows the November 2015 agreement between Cumberland and GEL to assume the remaining commercial rights to Omeclamox-Pak for the United States. The Company had previously signed an agreement with Pernix Therapeutics ('Pernix') to jointly commercialize the product in the United States in October 2013. As part of the November 2015 GEL Agreement, Cumberland and Pernix terminated their arrangements.

The $4.0 million upfront payment that the Company paid in October 2013 to Pernix along with the payments made to GEL during 2018 are included in product and license rights and are being amortized over the remaining expected useful life of the acquired asset. The Company evaluated the remaining expected useful life and maintained the existing estimated life of the product, June 2032. Omeclamox-Pak contributed $0.8 million, $0.6 million, and $1.8 million in net revenues during 2019, 2018, and 2017, respectively.

RediTrex

In November 2016, the Company announced an Agreement to acquire the exclusive U.S. rights to Nordic Group B.V.'s ('Nordic') injectable methotrexate product line as an asset purchase. The products are designed for the treatment of active rheumatoid arthritis, juvenile idiopathic arthritis, severe psoriatic arthritis, and severe disabling psoriasis.

Under the terms of the Agreement, Cumberland is responsible for the products' FDA submission and registration. As consideration for the license, at closing, Cumberland paid a deposit of $100,000. The Company also recorded a liability of $0.9 million that will be settled through 180,000 unvested restricted shares of Cumberland common stock that vest upon the FDA approval of the first Nordic product. Cumberland also agreed to provide Nordic a series of payments tied to the products' FDA approval, launch and achievement of certain sales milestones. Nordic is responsible for manufacturing and supply of the products.

On November 27, 2019, Cumberland received FDA approval of the pre-filled syringe. The 180,000 shares of restricted Cumberland common stock vested and were valued at $0.9 million on the vesting date. In addition, the FDA approval resulted in an additional $1.0 million liability to Nordic that will be paid during 2020. The value of the then unvested restricted Cumberland common stock shares was a liability of $1.1 million at December 31, 2018.

Vibativ

During November 2018, the Company closed on an agreement with Theravance Biopharma ('Theravance') to acquire the global responsibility for Vibativ including the marketing, distribution, manufacturing and regulatory activities associated with the brand. Vibativ is a patented, FDA approved injectable anti-infective for the treatment of certain serious bacterial infections including hospital-acquired and ventilator-associated bacterial pneumonia and complicated skin and skin structure infections. It addresses a range of Gram-positive bacterial pathogens, including those that are considered difficult-to-treat and multidrug-resistant. Cumberland acquired Vibativ to further add to its product offerings, increase its net revenue and positively contribute to the Company's operating results. Cumberland expects to deduct the goodwill acquired in the acquisition for tax purposes.

CUMBERLAND PHARMACEUTICALS INC. AND SUBSIDIARIES

Notes to Consolidated Financial Statements (Continued)

Cumberland has accounted for the transaction as a business combination in accordance with ASC 805 and the product sales are included in the results of operations subsequent to the acquisition date. The Company paid an upfront payment of $20.0 million at closing and a $5.0 million cash payment during early 2019. In addition, Cumberland agreed to pay a royalty of up to 20% on future net sales of the product. The future royalty payments were required to be recognized at their acquisition-date fair value as part of the contingent consideration transferred in the business combination.

The following table summarizes the initial payments and consideration for the business combination:

Consideration:
Cash paid at closing $ 20,000,000
Cash payment during early 2019 5,000,000
Fair value of contingent consideration – net sales royalty 9,182,000
Total consideration $ 34,182,000

The contingent consideration liability represents the future net sales royalty payments discussed above. Cumberland prepared the valuations of the contingent consideration liability and the intangible assets utilizing significant unobservable inputs. As a result, the valuations are classified as Level 3 fair value measurements. The Company will continue to evaluate the assets acquired and liabilities assumed during the measurement period.

The following table presents the changes in the Company's Level 3 contingent consideration liability that is measured at fair value on a recurring basis. The current and long-term portions of this liability are disclosed in Note 8. The contingent consideration earned and accrued in operating expenses is paid to the seller quarterly.

Contingent consideration liability
Balance at November 12, 2018 $ 9,034,000
Change in fair value of contingent consideration included in operating expenses (40,000)
Contingent consideration earned and accrued in operating expenses 508,000
Balance at December 31, 2018 9,502,000
Adjustment to initial fair value of the contingent consideration liability 148,000
Cash payment of royalty during the period (1,033,108)
Change in fair value of contingent consideration included in operating expenses (804,167)
Contingent consideration earned and accrued in operating expenses 820,864
Balance at December 31, 2019 $ 8,633,589

CUMBERLAND PHARMACEUTICALS INC. AND SUBSIDIARIES

Notes to Consolidated Financial Statements (Continued)

The following table summarizes the allocation of the fair values of the assets acquired as of the acquisition date for Vibativ:

Finished goods inventory $ 6,624,000
Work in process – unlabeled vials 3,970,000
Work in process – validation vials 1,827,000
Raw materials 9,129,000
Total inventory $ 21,550,000
Intellectual property amortizable intangible assets $ 11,750,000
Goodwill 882,000
Total intangibles and goodwill $ 12,632,000
Total assets acquired $ 34,182,000

The Company's contingent consideration liability is a Level 3 fair value measurement that is updated on a recurring basis at each reporting period using a valuation model. Consistent with Level 3 fair value measurements, there are significant inputs to the valuation model that are unobservable. The current portion of the contingent consideration liability is $2.4 million and the non-current portion is $6.3 million, as of December 31, 2019.

(4) Revenues

Product Revenues

The Company's net product revenues consisted of the following for the years ended December 31:

2019 2018 2017
Products:
Acetadote $ 3,824,449 $ 4,284,111 $ 6,576,720
Omeclamox-Pak 837,829 623,297 1,761,868
Kristalose 12,895,120 12,055,625 11,455,805
Vaprisol 936,615 1,763,874 1,576,222
Caldolor 5,222,281 5,001,997 4,178,443
Ethyol 12,774,831 10,545,906 10,835,038
Totect 369,912 850,965 3,992,467
Vibativ 8,691,550 5,075,057
Total net product revenues $ 45,552,587 $ 40,200,832 $ 40,376,563

Other Revenues

During 2019, Cumberland executed a License and Distribution agreement with HongKong WinHealth Pharma Group Co. Limited ('WinHealth') for our Caldolor and Acetadotebrands in China and Hong Kong. In conjunction with these new arrangements, the Company terminated a previous License and Distribution agreement with Gloria Pharmaceuticals Co ('Gloria Pharmaceuticals') for the two brands. In addition, we also signed a new License and Distribution agreement with DB Pharm Korea Co., Ltd. ('DB Pharm') for Vibativ in South Korea. As a result of these agreements, Cumberland recognized approximately $0.3 million of non-refundable up-front payments as other revenue in the consolidated statement of operations during 2019.

CUMBERLAND PHARMACEUTICALS INC. AND SUBSIDIARIES

Notes to Consolidated Financial Statements (Continued)

The Company has entered into agreements, beginning in 2012, with international partners for commercialization of the Company's products. The international agreements provide that each of the partners are responsible for seeking regulatory approvals for the products, and following approvals, each partner will handle ongoing distribution and sales in the respective international territories. The Company maintains responsibility for the intellectual property and product formulations. Under the international agreements, the Company is entitled to receive non-refundable up-front payments at the time the agreements are entered into and payments upon the partners' achievement of defined regulatory approvals and sales milestones. The Company will recognize revenue for these achievements once it is probable that these consideration amounts are no longer constrained. The Company is also entitled to receive royalties on future sales of the products under the agreements. The international agreements provide for $1.0 million in non-refundable up-front payments, milestone payments of up to $2.2 million related to regulatory approvals and up to $4.8 million in payments related to product sales. From 2012 through December 31, 2019, the Company has recognized a cumulative $1.2 million in upfront payments as other revenue and has recognized $0.1 million in revenue related to the milestone payments associated with these international agreements.

Other revenues during 2019, 2018 and 2017 also includes revenue generated by CET through grant funding from federal Small Business grant programs, and lease income generated by CET's Life Sciences Center and contract services. The Life Sciences Center is a research center that provides scientists with access to flexible lab space and other resources to develop biomedical products. Grant revenue from SBIR/STTR programs totaled approximately $1.3 million, $0.1 million, and $0.2 million for the years ending December 31, 2019, 2018 and 2017, respectively.

(5) Inventories

The Company's net inventories consisted of the following as of December 31:

2019 2018
Raw materials and work in process $ 19,345,723 $ 18,378,450
Consigned inventory 416,468 937,006
Finished goods, net of reserve 5,204,321 8,511,887
Total inventories 24,966,513 27,827,343
less non-current inventories (15,554,992) (15,749,000)
Total inventories classified as current $ 9,411,521 $ 12,078,343

The Company continually evaluates inventories for potential losses due to expired, short-dated or slow-moving inventory by comparing sales history and sales projections to the inventory on hand. When evidence indicates the carrying value of a product may not be recoverable, a charge is recorded to reduce the inventory to its current net realizable value. At December 31, 2019 and 2018, the Company had recognized and maintained cumulative charges for potential obsolescence and discontinuance losses of approximately $0.1 million and $0.3 million, respectively. At December 31, 2019 there were no cumulative obsolescence or discontinuance losses necessary.

In connection with the acquisition of certain product rights related to the Kristalose brand, the Company is responsible for the purchase of the active pharmaceutical ingredient ('API') for Kristalose and maintains the inventory at the third-party packagers. As the API is consumed in production, the value of the API is transferred from raw materials to finished goods. API for the Company's Vaprisol brand is also included in the raw materials inventory total at December 31, 2019 and 2018. Consigned inventory represents Authorized Generic inventory stored with Perrigo until shipment.

As part of the Vibativ acquisition, Cumberland acquired API and work in process inventories of $15.7 million that are classified as non-current inventories at December 31, 2018. At December 31, 2019, the Vibativ non-current inventory was $15.3 million. Although the Company did not have any finished goods included in the non-current

CUMBERLAND PHARMACEUTICALS INC. AND SUBSIDIARIES

Notes to Consolidated Financial Statements (Continued)

inventories at December 31, 2019, we had $0.8 million in Vibativ finished goods included at December 31, 2018. During 2019, Cumberland also obtained $0.3 million in non-current inventory for API related to its ifetroban clinical initiatives.

(6) Property and Equipment

Property and equipment consisted of the following at December 31:

Range of

useful lives

2019 2018
Computer equipment 3 – 5 years $ 1,260,630 $ 1,148,140
Office equipment 3 – 15 years 878,350 809,153
Furniture and fixtures 5 – 15 years 646,505 639,267
Leasehold improvements 3 – 15 years, or remaining lease term 1,356,640 1,299,363

Total property and

equipment, gross

4,142,125 3,895,923

Less: accumulated depreciation

and amortization

(3,394,329) (3,124,710)

Total property and

equipment, net

$ 747,796 $ 771,213

Depreciation expense, including amortization expense related to leasehold improvements, is included in general and administrative expense in the consolidated statements of operations. Depreciation expense was as follows for the years ended December 31:

2019 2018 2017
Depreciation expense $ 269,619 $ 213,237 $ 211,532

CUMBERLAND PHARMACEUTICALS INC. AND SUBSIDIARIES

Notes to Consolidated Financial Statements (Continued)

(7) Intangible Assets and Goodwill

Intangible assets and Goodwill consisted of the following at December 31:

2019 2018
Product and license rights $ 37,400,742 $ 36,573,941
Less: accumulated amortization (11,499,141) (8,405,188)
Total product and license rights 25,901,601 28,168,753
Patents 9,882,511 9,428,266
Less: accumulated amortization (5,127,878) (4,087,273)
Total patents 4,754,633 5,340,993
Trademarks 273,110 154,373
Less: accumulated amortization (9,020) (9,020)
Total trademarks 264,090 145,353
Total intangible assets $ 30,920,324 $ 33,655,099
Goodwill $ 882,000 $ 784,000

During 2013, the Company entered into an agreement with Pernix to distribute and promote the branded prescription product Omeclamox-Pak. Il $4.0 millionupfront payment the Company paid to Pernix during October 2013 and the $2.3 million payments made to GEL during 2018 (discussed more fully in Note 3) are included in product and license rights and are being amortized through June 2032, the remaining expected useful life of the acquired asset.

During 2014, the Company acquired the rights of the branded prescription product Vaprisol from Astellas. The intangible asset value is $3.0 million and is included in product and license rights. The asset is being amortized through February 2022, the remaining expected useful life of the acquired asset, which coincides with the life of the primary intellectual property asset.

As discussed in Note 3, in November 2016, the Company acquired the U.S. rights to Nordic Group B.V.'s injectable methotrexate product line as an asset purchase. The agreement requires the Company to provide unvested restricted shares of Cumberland common stock and make a series of payments tied to the products' FDA approval, launch and achievement of certain sales milestones. The payments are being treated as consideration for the assets acquired and are being capitalized and amortized over the expected useful life of the acquired asset. To date, the intangible assets related to the product include the $100,000 deposit paid at closing, the 180,000 restricted shares valued at $0.9 million that vested upon the November 2019 FDA approval and the additional $1.0 million owed to Nordic during 2020, also based on the FDA approval.

As discussed in Note 3, during November 2018, the Company acquired Vibativ from Theravance. This resulted in amortizable intangible assets related to the product rights of $11.8 million and goodwill of $0.9 million. The intangible assets are being amortized through November 2028, the expected useful life of the acquired asset. The $0.1 million increase in goodwill during 2019 was a result of changes in the purchase price allocation during the measurement period.

During 2019 and 2018, the Company recorded an additional $0.7 million and $0.4 million, respectively, in intangible assets for patents, trademarks and capitalized patent costs, including amounts incurred in the protection of the Company's intellectual property. These costs will be amortized over the remaining expected useful life of the associated patents.

CUMBERLAND PHARMACEUTICALS INC. AND SUBSIDIARIES

Notes to Consolidated Financial Statements (Continued)

Amortization expense related to product and license rights, trademarks and patents were as follows for the years ended December 31:

2019 2018 2017
Amortization expense $ 4,134,557 $ 2,769,466 $ 2,436,222

The expected amortization expense for the Company's current balance of intangible assets are as follows:

Year ending December 31:
2020 $ 4,286,336
2021 4,084,702
2022 3,530,879
2023 3,743,526
2024 and thereafter 15,274,881
$ 30,920,324

(8) Other Current and Other Long-term Liabilities

Other current liabilities consisted of the following at December 31:

Other current liabilities 2019 2018

Rebates, product returns, administrative fees

and service fees

$ 4,825,657 $ 5,635,972
Employee wages and benefits 1,295,905 1,263,426
Stock payable 1,085,400
Current portion of accrued contingent consideration 2,374,776 2,290,000
Deferred acquisition liability 5,000,000
Accrued inventory purchases 829,047 434,405
Accrued payment for asset purchase 1,000,000
Other 991,973 1,001,724
Total other current liabilities $ 11,317,358 $ 16,710,927
Other long-term liabilities 2019 2018
Noncurrent portion of accrued contingent consideration $ 6,258,813 $ 7,212,000
Deferred compensation 2,278,164 1,588,123
Other 200,346 519,020
Total other long-term liabilities $ 8,737,323 $ 9,319,143

CUMBERLAND PHARMACEUTICALS INC. AND SUBSIDIARIES

Notes to Consolidated Financial Statements (Continued)

(9) Debt

On May 10, 2019, the Company entered into a third amendment ('Third Amendment') to the Revolving Credit Loan Agreement, dated July 28, 2017, with Pinnacle Bank ('Pinnacle Agreement'). The Third Amendment extended the term of the Pinnacle Agreement through July 31, 2021 as well as modified certain definitions and terms of the existing financial covenants, including the definition of the Funded Debt Ratio and the compliance target of the Tangible Capital Ratio. Both Third Amendment modifications were related to the Vibativ transaction. Under the Pinnacle Agreement, Cumberland was initially subject to one financial covenant, the maintenance of a Funded Debt Ratio, as such term is defined in the agreement and determined on a quarterly basis. On August 14, 2018, the Company amended the Pinnacle Agreement ('First Amendment') to replace the single financial covenant with the maintenance of either the Funded Debt Ratio or a Tangible Capital Ratio, as defined in the First Amendment. The Company achieved compliance with the Tangible Capital Ratio financial covenant as of December 31, 2019.

The initial revolving line of credit under the Pinnacle Agreement was for up to an aggregate principal amount of $12.0 million with the ability to increase the principal amount available for borrowing up to $20.0 million, upon the satisfaction of certain conditions. On October 17, 2018, the Company entered into a second amendment ('Second Amendment') which increased the maximum aggregate principal available for borrowing under the Pinnacle Agreement to $20.0 million.

The Company had $18.5 million in borrowings under the Pinnacle Agreement at December 31, 2019 and $20.0 million at December 31, 2018.

The interest rate on the Pinnacle Agreement is based on LIBOR plus an interest rate spread. There is no LIBOR minimum and the LIBOR pricing provides for an interest rate spread of 1.75% to 2.75% (representing an interest rate of 4.5% at December 31, 2019). In addition, a fee of 0.25% per year is charged on the unused line of credit. Interest and the unused line fee are payable quarterly. Borrowings under the line of credit are collateralized by substantially all of our assets.

(10) Shareholders' Equity

(a) Initial Public Offering

On August 10, 2009, the Company completed its initial public offering of 5,000,000 shares of common stock at a price of $17.00 per share, raising gross proceeds of $85.0 million. After deducting underwriting discounts of approximately $6.0 million and offering costs incurred of approximately $4.2 million, the net proceeds to the Company were approximately $74.8 million. Contemporaneously with the offering, each outstanding share of preferred stock was automatically converted into two million shares of common stock.

(b) Preferred Stock

The Company is authorized to issue 20,000,000 shares of preferred stock. The Board of Directors is authorized to divide these shares into classes or series, and to fix and determine the relative rights, preferences, qualifications and limitations of the shares of any class or series so established. At December 31, 2019 and 2018, there was no preferred stock outstanding.

(c) Common Stock

During 2019, 2018 and 2017, the Company issued 225,536 shares, 170,759 shares, and 146,275 shares of common stock, respectively, as a result of restricted shares vesting as well as other common share issuances. Cumberland issued 3,409 common shares under option exercise transactions during 2016. There were no option exercise transactions during 2019, 2018 and 2017.

CUMBERLAND PHARMACEUTICALS INC. AND SUBSIDIARIES

Notes to Consolidated Financial Statements (Continued)

In January 2018, the Company's Form S-3 or Shelf Registration associated with the sale of up to $100 million in corporate securities was declared effective. The Shelf Registration also included an At-the-Market ('ATM') feature enabling the Company to sell common shares at market prices, along with an agreement with B. Riley FBR to support such a placement of shares.

(d) Warrants

In 2006, the Company signed a new line of credit agreement along with a term loan agreement with a financial institution. In conjunction with these agreements, the Company issued warrants to purchase up to 3,958 shares of common stock at $9.00 per share within 10 years of issuance. All of these warrants expired during 2017.

In connection with the amendment to the debt agreements in 2009, the Company issued warrants to purchase up to 7,500 shares of common stock at $17.00 per share that expired in July 2019. As of December 31, 2019, there were no outstanding warrants.

(e) Share Repurchases

The Company currently has a share repurchase program to repurchase up to $10 million of its common stock pursuant to Rule 10b-18 of the Securities Act. In January 2019, the Company's Board of Directors established the current $10 million repurchase program to replace the prior authorizations. The Company repurchased 623,478 shares, 443,041 shares and 547,376 shares of common stock for approximately $3.5 million, $2.9 million, and $3.7 million during the years ended December 31, 2019, 2018 and 2017, respectively. There remains $8.0 million available under the current repurchase program available for share repurchases at December 31, 2019.

(f) Cumberland Emerging Technologies

In April 2019, Cumberland Emerging Technologies ('CET'), our majority-owned subsidiary, entered into an agreement with WinHealth whereby WinHealth made a$1 million investment through the purchase of shares of CET stock. As part of the agreement, WinHealth obtained a Board position at CET and the first opportunity to license CET products for the Chinese market. In connection with WinHealth's investment in CET, the Company also made an additional $1 million investment in CET. Cumberland purchased additional CET shares through contribution of$0.3 million in cash and a conversion of $0.7 million in intercompany loans payable. Upon completion of the additional investment by WinHealth and Cumberland, Gloria Pharmaceuticals agreed to return its shares in CET in exchange for consideration of $0.8 million. After the additional investment, the Company's ownership in CET is 85%. As CET is a consolidated subsidiary, the Company reports the operating results of CET and allocates the noncontrolling interests to the non-majority partners.

(g) Cumberland Foundation

In December 2017, the Company formed the Cumberland Pharma Foundation (the 'Foundation') to serve as a vehicle to facilitate the ongoing philanthropic endeavors of Cumberland Pharmaceuticals Inc.

The Foundation was formed as a nonprofit corporation designed to qualify as a tax-exempt organization pursuant to Section 501(a) of the Internal Revenue Code. The Foundation's Board of Directors is comprised of Cumberland Pharmaceuticals executives who are responsible for overseeing the Foundation's ongoing activities including charitable contributions.

In 2018, Cumberland provided a grant of 50,000 shares of the Company's common stock to the Foundation. The shares will address the ongoing financial needs of the organization, with most of the shares expected to be held for the opportunity to realize long term appreciation to support the Foundation's future. The Foundation maintains separate financial statements and its ongoing operations will not impact the financial statements of Cumberland Pharmaceuticals. Initial annual grants by the Foundation have been and are expected to remain consistent with the historic level of contributions made by Cumberland Pharmaceuticals. During 2019, Cumberland Pharmaceuticals committed approximately $50,000 in cash contributions to be paid to the Foundation during 2020.

CUMBERLAND PHARMACEUTICALS INC. AND SUBSIDIARIES

Notes to Consolidated Financial Statements (Continued)

(h) Nordic Group B.V.

On November 27, 2019, Cumberland received approval from the FDA for the pre-filled syringe of the Methotrexate product. With this approval, Nordic's 180,000 shares of Cumberland's common stock became vested. The value of these shares at the date of approval was $0.9 million.

(11) Earnings (Loss) Per Share

The following table shows the computation of the numerator and the denominator used to calculate diluted earnings (loss) per share for the years ended December 31:

2019 2018 2017
Numerator:
Net income (loss) attributable to common shareholders $ (3,537,759) $ (6,963,068) $ (7,978,633)
Denominator:
Weighted-average shares outstanding – basic 15,396,098 15,614,052 15,911,577
Dilutive effect of restricted stock and stock options
Weighted-average shares outstanding – diluted 15,396,098 15,614,052 15,911,577

The Company's anti-dilutive restricted shares and stock options outstanding were as follows for the years ended December 31:

2019 2018 2017
Anti-dilutive shares and options 4,000 41,650 18,325

CUMBERLAND PHARMACEUTICALS INC. AND SUBSIDIARIES

Notes to Consolidated Financial Statements (Continued)

(12) Income Taxes

The components of the Company's net deferred tax assets at December 31 are as follows:

2019 2018
Deferred Tax Assets
Net operating loss and tax credits $ 16,964,685 $ 16,410,403
Property and equipment and intangibles 227,072 236,318
Allowance for accounts receivable 257,564 251,068
Reserve for expired product 469,466 558,484
Inventory 35,227 193,150
Deferred charges 845,765 910,577
Cumulative compensation costs incurred on deductible equity awards 1,047,149 884,049
Total deferred tax assets 19,846,928 19,444,049
Deferred Tax Liabilities
Intangible assets (1,313,965) (1,974,787)
Net deferred tax assets, before valuation allowance 18,532,963 17,469,262
Less: deferred tax asset valuation allowance (18,511,161) (17,382,052)
Net deferred tax assets $ 21,802 $ 87,210

The following table summarizes the amount and year of expiration of the Company's federal and state net operating loss carryforwards as of December 31, 2019:

Years of expiration Federal State
2020 $ $ 13,115
2021 – 2029 49,392,824
2030 44,153,819 461,280
2031 – 2039 7,534,351 9,947,070
Indefinite Period 5,493,258 383,869
Total federal and state net operating loss carryforwards $ 57,181,428 $ 60,198,158

CUMBERLAND PHARMACEUTICALS INC. AND SUBSIDIARIES

Notes to Consolidated Financial Statements (Continued)

Income tax (expense) benefit includes the following components for the years ended December 31:

2019 2018 2017
Current:
Federal $ 65,408 $ $
State and other 79,316 (16,636) (59,243)
Total current income tax (expense) benefit 144,724 (16,636) (59,243)
Deferred:
Federal (65,408) (3,682,772)
State (432,874)
Total deferred income tax (expense) benefit (65,408) (4,115,646)
Total income tax (expense) benefit $ 79,316 $ (16,636) $ (4,174,889)

The Company's effective income tax rate for 2019, 2018 and 2017 reconciles with the federal statutory tax rate as follows:

2019 2018 2017
Federal tax expense at statutory rate 21 % 21 % 34 %
State income tax expense (net of federal income tax benefit) 4 % 4 % 4 %
Permanent differences associated with general business credits 7 % 1 % 1 %
Change in valuation allowance (31) % (25) % (148) %
Change in tax rate % % 2 %
Other permanent differences 1 % (1) % 1 %
Other % % (2) %
Net income tax expense 2 % % (108) %

In 2017, the Company determined that it was not more likely than not that its net deferred tax assets would be realized. As such, the Company's income tax provision for the year ended December 31, 2017 reflected a full valuation allowance against net deferred tax assets with the exception of the deferred tax asset for alternative minimum tax ('AMT') credit carryforwards discussed further below. The Company's position is unchanged as of both December 31, 2018 and December 31, 2019.

On December 22, 2017, the U.S. government enacted comprehensive tax legislation commonly referred to as the Tax Cuts and Jobs Act ('the Tax Act'). The Tax Act makes broad and complex changes to the U.S. tax code, including, but not limited to, (1) reducing the U.S. federal corporate tax rate to 21%; (2) eliminating the corporate alternative minimum tax ('AMT') and changing how AMT credits can be realized; (3) capital expensing; and (4) creating new limitations on deductible interest expense and executive compensation.

CUMBERLAND PHARMACEUTICALS INC. AND SUBSIDIARIES

Notes to Consolidated Financial Statements (Continued)

In connection with our analysis of the impact of the Tax Act, we recorded a net tax benefit of $0.1 million in the period ended December 31, 2017. This net tax benefit consisted entirely of the release of the valuation allowance against AMT credits that will be realizable under the Tax Act in future periods.

The Company expects it will continue to pay minimal taxes in future periods through the continued utilization of net operating loss carryforwards, as it is able to achieve taxable income through its operations.

The Company is no longer subject to U.S. federal tax examinations for tax years before 2016, and with few exceptions, the Company is not subject to examination by state tax authorities for tax years which ended before 2016. Loss carryforwards and credit carryforwards generated or utilized in years earlier than 2016 remain subject to examination and adjustment. During 2012, the 2009 federal tax return was examined by the Internal Revenue Service with no significant findings or adjustments. The Company has no unrecognized tax benefits in 2019, 2018 and 2017.

(13) Stock-Based Compensation Plans

The Company has grants outstanding under three equity compensation plans, with two of the plans available for future grants of equity compensation awards to employees, consultants and directors. All of the equity plans were approved by shareholders. The 2007 Long-Term Incentive Compensation Plan (the '2007 Plan') and the 2007 Directors' Incentive Plan (the 'Directors' Plan') superseded the 1999 Stock Option Plan. The 2007 Plan and the Directors' Plan provide for the issuance of stock options, stock appreciation rights and restricted stock. Vesting is determined on a grant-by-grant basis in accordance with the terms of the plans and the related grant agreements. The Company has reserved 2.4 million shares of common stock for issuance under the 2007 Plan and 250,000 shares for issuance under the Directors' Plan.

The exercise price of stock options is generally 100% of the fair market value of the underlying common stock on the grant date. The maximum contractual term of stock options is ten years from the date of grant, except for incentive stock options granted to 10% shareholders, which is five years.

During 2011, the Company began issuing shares of restricted stock with no exercise price to employees and directors. Restricted stock issued to employees generally cliff-vests on the fourth anniversary of the date of grant. Restricted stock issued to directors vests on the one year anniversary of the date of grant.

Stock compensation expense is presented as a component of general and administrative expense in the consolidated statements of operations. Stock compensation expense consisted of the following for the years ended December 31:

2019 2018 2017
Share-based compensation – employees $ 1,481,016 $ 1,244,606 $ 1,032,094
Share-based compensation – nonemployees 4,882 120,092 82,969
Share-based compensation – foundation contribution $ 372,500
Total share-based compensation $ 1,485,898 $ 1,364,698 $ 1,487,563

At December 31, 2019, there was approximately $2.1 million of unrecognized compensation cost related to share-based payments, which is expected to be recognized over a weighted-average period of 2.5 years. This amount relates primarily to unrecognized compensation cost for employee restricted stock awards.

CUMBERLAND PHARMACEUTICALS INC. AND SUBSIDIARIES

Notes to Consolidated Financial Statements (Continued)

Stock Options

Stock option activity for 2019 and 2018 was as follows:

Number of

shares

Weighted-average exercise price per share

Weighted-

average

remaining

contractual

term (years)

Aggregate

intrinsic

value

Outstanding, December 31, 2017 5,800 $ 13.00 1.9 $
Options granted
Options exercised
Options forfeited or expired
Outstanding, December 31, 2018 5,800 13.00 0.9
Options granted
Options exercised
Options forfeited or expired (5,800) 13.00
Outstanding, December 31, 2019 0
Exercisable at December 31, 2019 $ 0 $

The Company did not grant any stock options and there were no options exercised during 2019, 2018 and 2017. Information related to the stock option plans during 2019, 2018 and 2017 was as follows:

2019 2018 2017
Intrinsic value of options exercised $ $ $

Weighted-average fair value of

options exercised

$ $ $

Restricted Stock Awards

Restricted stock activity was as follows:

Number

of shares

Weighted-

average

grant-date

fair value

Nonvested, December 31, 2017 767,845 $ 5.61
Shares granted 261,680 6.66
Shares vested (170,759) 4.79
Shares forfeited (25,025) 6.19
Nonvested, December 31, 2018 833,741 6.09
Shares granted 229,669 5.95
Shares vested (225,536) 6.71
Shares forfeited (22,925) 6.20
Nonvested, December 31, 2019 814,949 $ 5.88

CUMBERLAND PHARMACEUTICALS INC. AND SUBSIDIARIES

Notes to Consolidated Financial Statements (Continued)

The fair value of restricted stock granted was based on the closing market price of the Company's common stock on the date of grant. The restricted stock grants are included in the diluted weighted shares outstanding computation until they cliff-vest. Once vested they are included in the basic weighted shares outstanding computation.

(14) Employee Benefit Plans

The Company sponsors an employee benefit plan that was established on January 1, 2006, the Cumberland Pharmaceuticals 401(k) Plan (the 'Plan'), under Section 401(k) of the Internal Revenue Code of 1986, as amended, for the benefit of all employees over the age of 21, having been employed by the Company for at least six months. The Plan provides that participants may contribute up to the maximum amount of their compensation as set forth by the Internal Revenue Service each year. Employee contributions are invested in various investment funds based upon elections made by the employees. During 2019, 2018 and 2017, the Company contributed approximately $50,000 in each year to the Plan as an employer match of participant contributions.

In 2012 and 2013, the Company established non-qualified unfunded deferred compensation plans that allow participants to defer receipt of a portion of their compensation. The liability under the plans, reflected in other long term liabilities in the consolidated balance sheet, was $2.3 million and $1.6 million as of December 31, 2019 and 2018, respectively. The Company had assets consisting of company-owned life insurance contracts generally designated to pay benefits of the deferred compensation plans reflected in other assets in the consolidated balance sheet of $3.1 million and $2.3 million as of December 31, 2019 and 2018, respectively.

(15) Leases

The Company is obligated under long-term real estate leases for corporate office space that was extended during the third quarter of 2015. Prior to this extension, the lease would have expired in October 2016, the lease is now set to expire in October 2022. In addition, the research lab space at CET, under an agreement amended in July 2012, is leased through April 2023, with an option to extend the lease through April 2028. The Company also subleases a portion of the space under these leases.

Rent expense is recognized over the expected term of the lease, including renewal option periods, if applicable, on a straight-line basis as a component of general and administrative expense. Rent expense and sublease income as follows for the years ended December 31:

2019 2018 2017
Rent expense $ 1,246,143 $ 1,136,610 $ 1,074,437
Sublease income $ 688,020 $ 662,358 $ 573,494

In March 2016, the FASB issued ASU 2016-02. ASU 2016-02's core principle is to increase transparency and comparability among organizations by recognizing lease assets and liabilities on the balance sheet and disclosing key information. The Company adopted ASU 2016-02 under the alternative transition method (the effective date approach). It allowed the Company to initially apply the new lease guidance at the adoption date (rather than at the beginning of the earliest period presented). Prior periods have not been adjusted.

The primary effect of adopting ASU 2016-02 to the Company was to record right-of-use assets and obligations for the leases currently classified as operating leases. The Company's significant operating leases include the lease of approximately 25,500 square feet of office space in Nashville, Tennessee for its corporate headquarters. This lease currently expires in October 2022. The operating leases also include the lease of approximately 14,200 square feet of wet laboratory and office space in Nashville, Tennessee by Cumberland Emerging Technologies ('CET'),

CUMBERLAND PHARMACEUTICALS INC. AND SUBSIDIARIES

Notes to Consolidated Financial Statements (Continued)

our majority-owned subsidiary, where it operates the CET Life Sciences Center. This lease currently expires in April 2023. The Company did not have any leases classified as finance leases at January 1, 2019 or December 31, 2019. The new lease accounting standard did not have a significant impact on the Company's Condensed Consolidated Statements of Operations and Comprehensive Income (Loss) for any period presented.

The Company elected the package of practical expedients offered in the transition guidance which allows management not to reassess lease identification, lease classification and initial direct costs at the adoption date.

These operating leases resulted in initial ROU assets of $3.6 million and lease liabilities of $3.8 million as of January 1, 2019 for non-cancelable operating leases with original lease terms in excess of one year.

Operating lease liabilities were recorded as the present value of remaining lease payments not yet paid for the lease term discounted using the incremental borrowing rate associated with each lease. Operating lease right-of-use assets represent operating lease liabilities adjusted for lease incentives and initial direct costs. As the Company's leases do not contain implicit borrowing rates, the incremental borrowing rates were calculated based on information available at January 1, 2019. Incremental borrowing rates reflect the Company's estimated interest rates for collateralized borrowings over similar lease terms. The weighted-average remaining lease term is 3.4 years and the weighted-average incremental borrowing rate used to discount the present value of the remaining lease payments is 7.42%.

Lease Position

At December 31, 2019, the Company recorded the following on the Condensed Consolidated Balance Sheet:

Right-of-Use Assets Balance Sheet Classification December 31, 2019
Operating lease right-of-use assets Other noncurrent assets $ 2,960,569
Total $ 2,960,569
Lease Liabilities Balance Sheet Classification December 31, 2019
Current:
Operating lease liabilities Other current liabilities $ 920,431
Noncurrent:
Operating lease liabilities Other noncurrent liabilities 2,076,472
Total $ 2,996,903

CUMBERLAND PHARMACEUTICALS INC. AND SUBSIDIARIES

Notes to Consolidated Financial Statements (Continued)

Cumulative future minimum sublease income under non-cancelable operating subleases totals approximately $0.7 million and will be paid through the leases ending in October 2022 and April 2023. Future minimum lease payments under non-cancelable operating leases (with initial or remaining lease terms in excess of one year) are as follows:

As of December 31, 2019:
2020 $ 1,120,066
2021 1,144,889
2022 1,019,313
2023 92,478
After 2023
Total future minimum lease payments 3,376,746
Less Interest (379,843)
Present value of lease liabilities $ 2,996,903

The Company's future minimum lease commitments, under Topic 840, predecessor to Topic 842, are as follows:

As of December 31, 2018:
2019 $ 959,902
2020 980,720
2021 1,001,603
2022 871,969
2023 44,508
After 2023
Total future minimum lease payments $ 3,858,702

(16) Fair Value of Financial Instruments

The Company owns marketable securities that are solely classified as trading securities as of December 31, 2019. All of these securities had a maturity date of less than ninety days and classified as cash and cash equivalents at December 31, 2019. There were no transfers of assets between levels within the fair value hierarchy. The following table summarizes the fair value of these marketable securities by level within the fair value hierarchy:

December 31, 2019 December 31, 2018
Level 1 Level 2 Total Level 1 Level 2 Total
U.S. Treasury notes and bonds $ $ $ $ 5,034,955 $ $ 5,034,955
SBA loan pools – variable rate 2,504,551 2,504,551
Short-term cash investments 751,173 751,173
Commercial Paper 2,119,607 2,119,607
Total fair value of marketable securities $ $ 2,119,607 $ 2,119,607 $ 5,034,955 $ 3,255,724 $ 8,290,679

The fair values of all other financial instruments outstanding as of December 31, 2019 and 2018 approximate their carrying values. There were no changes to the valuation techniques for the Level 2 marketable securities during 2019 or 2018.

CUMBERLAND PHARMACEUTICALS INC. AND SUBSIDIARIES

Notes to Consolidated Financial Statements (Continued)

(17) Market Concentrations

The Company is focused on the acquisition, development and commercialization of branded prescription products. The Company's principal financial instruments subject to potential concentration of credit risk are accounts receivable, which are unsecured, and cash equivalents. The Company's cash equivalents consist primarily of money market funds. Certain bank deposits may be in excess of the insurance limits provided by the Federal Deposit Insurance Corporation.

The Company's primary customers are wholesale pharmaceutical distributors in the U.S. Total revenues by customer for each customer representing 10% or more of consolidated revenues are summarized below for the years ended December 31:

2019 2018 2017
Customer 1 26% 25% 25%
Customer 2 25% 24% 22%
Customer 3 16% 26% 25%
Customer 4 14% 11% *%

*: less than 10% of total

The Company's accounts receivable, net of allowances, due from the customers representing 10% or more of consolidated revenue was 72% and 78% at December 31, 2019 and 2018, respectively.

(18) Manufacturing and Supply Agreements

The Company utilizes one or two primary suppliers to manufacture each of its products and product candidates. Although there are a limited number of manufacturers of pharmaceutical products, the Company believes it could utilize other suppliers to manufacture its prescription products on comparable terms. A change in suppliers, problems with its third-party manufacturing operations or related production capacity, or contract disputes with suppliers could cause a delay in manufacturing or shipment of finished goods and possible loss of sales, which could adversely affect operating results.

(19) Employment Agreements

The Company has entered into employment agreements with all its full-time employees. Each employment agreement provides for a salary for services performed, a potential annual bonus and, if applicable, a grant of restricted common shares pursuant to a restricted stock agreement.

(20) Discontinued Operations

In 2016, Cumberland entered into an agreement with Clinigen Group Plc ('Clinigen') for the rights and responsibilities associated with the commercialization of Ethyol in the United States. In 2017, the Company entered into another agreement with Clinigen for the rights and responsibilities associated with the commercialization of Totect in the United States. Ethyol and Totect are collectively referred to herein as the 'Products.'

Early in 2019, Cumberland announced a strategic review the Company's brands, capabilities, and international partners. This review followed an accelerated business development initiative, which resulted in a series of transactions. Because of that progress, Cumberland felt that it was prudent to take a fresh look at our product portfolio, partners, and organization to ensure proper focus and capabilities. In May 2019 following the strategic review, Cumberland entered into an agreement with Clinigen to return the exclusive rights to the Products (the 'Agreement'). The Agreement provided for a conclusion of the Company's arrangements with Clinigen effective September 30, 2019. Under the terms of the Agreement, Cumberland will no longer distribute the Products after the

CUMBERLAND PHARMACEUTICALS INC. AND SUBSIDIARIES

Notes to Consolidated Financial Statements (Continued)

transition date and will receive $5 million in financial consideration from Clinigen, paid over a two-year period. Cumberland agreed not to sell competing products during the same two-year period.

In September 2019, Clinigen and Cumberland completed an amendment to the Agreement, whereby the transition date was changed to late December 2019. Under the final terms of the amended Agreement, the Company returned the Product rights to Clinigen on December 31, 2019. Except for the Products' inventory as of December 31, 2019, no other operating assets and no liabilities were transferred to Clinigen.

The exit from the Ethyol and Totect Products meets the accounting criteria to be reported as discontinued operations. December 31, 2019, as the transition date, was the final day Cumberland was responsible for the Products. Cumberland was responsible for the Products through December 31, 2019 and beginning on January 1, 2020, the Products' rights transitioned back to Clinigen. As a result, January 1, 2020, was the first day of discontinued operations for the Ethyol and Totect products.

(21) Commitments and Contingencies

Commitments

In connection with the acquisition of certain Kristalose assets during 2011, the Company was required to make quarterly payments based on a percentage of Kristalose net sales through November 2018. The payments were treated as consideration for the assets acquired and were capitalized. They are being amortized over the remaining expected useful life of the acquired asset, currently through 2026.

In connection with its licensing agreements for Caldolor, the Company is required to pay royalties based on net sales over the life of the product. Royalty expense is recognized as a component of selling and marketing expense in the period that revenue is recognized.

In connection with its licensing agreements for Ethyol and Totect, the Company was required to pay royalties based on net sales. The royalty expense was recognized as a component of selling and marketing expense in the period the associated revenue was recognized through the end of the licensing period, December 31, 2019.

In connection with the acquisition of Vibativ, the Company is required to pay royalties based on net sales of the product. At the purchase date, Cumberland recorded the fair value of this liability and will continue to evaluate the liability each period and the royalty expense is recognized as a component of selling and marketing expense in the period that the change in fair value is recognized.

Legal Matters

Cumberland has a number of Patents issued through the United States Patent and Trademark Office (the 'USPTO') including U.S. Patent number 8,148,356 (the '356 Acetadote Patent') which is assigned to the Company. The claims of the 356 Acetadote Patent encompass the new Acetadote formulation and include composition of matter claims. Following its issuance, the 356 Acetadote Patent was listed in the FDA Orange Book. The 356 Acetadote Patent is scheduled to expire in May 2026, which time period includes a 270-day patent term adjustment granted by the USPTO.

Since 2012, Cumberland has to continued to vigorously defend and protect its Acetadote product and related intellectual property rights including the use of all its legal options.

The Company is a party to various other legal proceedings in the ordinary course of its business. In the opinion of management, the liability associated with these matters, will not have a material adverse effect on the Company's consolidated financial position, results of operations or cash flows.

CUMBERLAND PHARMACEUTICALS INC. AND SUBSIDIARIES

Notes to Consolidated Financial Statements (Continued)

(22) Quarterly Financial Information (Unaudited)

The following table sets forth the unaudited operating results for each fiscal quarter of 2019 and 2018:

First

Quarter

Second

Quarter

Third

Quarter

Fourth

Quarter

Total
2019:
Net revenues $ 11,902,747 $ 11,580,600 $ 10,371,918 $ 13,678,372 $ 47,533,637
Operating income (loss) (176,796) (601,715) (1,847,085) (997,409) (3,623,005)
Net income (loss) attributable to common shareholders (73,878) (549,507) (1,953,668) (960,706) (3,537,759)

Earnings (loss) per share attributable to common shareholders (1)

Basic $ $ (0.04) $ (0.13) $ (0.06) $ (0.23)
Diluted $ $ (0.04) $ (0.13) $ (0.06) $ (0.23)
2018:
Net revenues $ 8,587,605 $ 10,163,724 $ 8,492,530 $ 13,497,906 $ 40,741,765
Operating income (loss) (2,452,222) (868,978) (1,806,883) (2,262,689) (7,390,772)
Net income (loss) attributable to common shareholders (2,379,239) (720,688) (1,643,044) (2,220,097) (6,963,068)

Earnings (loss) per share attributable to common shareholders (1)

Basic $ (0.15) $ (0.05) $ (0.11) $ (0.14) $ (0.45)
Diluted $ (0.15) $ (0.05) $ (0.11) $ (0.14) $ (0.45)

(1) Due to the nature of interim earnings per share calculations, the sum of the quarterly earnings (loss) per share amounts may not equal the reported earnings (loss) per share for the full year.

CUMBERLAND PHARMACEUTICALS INC. AND SUBSIDIARIES

Notes to Consolidated Financial Statements (Continued)

(23) Subsequent events

On March 11, 2020, the World Health Organization declared the outbreak of a novel coronavirus ('COVID-19') as a global pandemic, which continues to spread throughout the United States and around the world. As of March 20, 2020, the Company is aware of changes in its business as a result of COVID-19 but uncertain of the impacts of those changes on its consolidated statements of position, operations or cash flows. Management believes any disruption, when and if experienced, could be temporary; however, there is uncertainty around when any disruption might occur, the duration and hence the potential impact. As a result, we are unable to estimate the potential impact on our business as of the date of this filing.

Schedule II

CUMBERLAND PHARMACEUTICALS INC. AND SUBSIDIARIES

Valuation and Qualifying Accounts

Years ended December 31, 2019, 2018 and 2017

Descrizione

Balance at

beginning of

period

Charged to

costs and

expenses

Charged to

altro

accounts

Deductions

Balance at

end of period

Allowance for uncollectible amounts, cash discounts, chargebacks, and credits issued for damaged products:

For the years ended

December 31:

2017 $ 449,859 $ 5,066,526 $ $ (5,008,851) (1) $ 507,534
2018 507,534 5,932,248 (5,446,442) (1) 993,340
2019 993,340 7,010,141 (7,195,470) (1) 808,011
Valuation allowance for deferred tax assets:

For the years ended

December 31:

2017 $ 388,500 $ (665,039) (2) $ 15,908,774 $ $ 15,632,235
2018 15,632,235 1,749,817 17,382,052
2019 17,382,052 1,129,109 18,511,161

(1) Composed of actual returns and credits for chargebacks and cash discounts.

(2) Amount includes $4,202,854 related to increase in the valuation allowance during the year, net of $4,867,893 related to the revaluation of deferred income tax balances for new rates under the Tax Act.

Mr. A.J. Kazimi

Re: Employment of A.J. Kazimi as Chief Executive Officer by Cumberland Pharmaceuticals Inc.

Effective January 1, 2020, this letter agreement (the 'Agreement') will evidence the terms and conditions under which you will be employed by Cumberland Pharmaceuticals Inc. (the 'Company') In consideration of your appointment as Chief Executive Officer of the Company, and other good and valuable consideration, the receipt and sufficiency of which is hereby acknowledged, the parties agree as follows:

1. Compensation.The Company agrees to compensate you as follows:

(a) The Company agrees to pay you on a salary basis for services performed based on an annual rate of five hundred eighty-nine thousand five hundred dollars ($589,500.00), payable in arrears in equal monthly installments on the 25esimoday of each calendar month of 2020. For each year, thereafter, you will be paid on a salary basis for services performed based on an annual rate determined by the Company in its sole discretion; provided, however, that any obligation to make payments under this Section 1(a) will cease upon termination of your employment for any reason. Notwithstanding the foregoing, nothing in this Section 1(a) alters or is intended to alter the at-will nature of your employment as described in Section 3 of this Agreement.

(b) You will be eligible to participate in any Company-wide employee benefits as approved by the Board of Directors. The terms of your eligibility and participation will be governed by the provisions of the employee benefit plans, as such plans may be amended from time to time in the discretion of the Company's Board of Directors.

(c) You may be eligible for any Company bonus program, based upon performance in meeting your individual objectives and the Company's overall performance, both as determined and approved by the Board of Directors of the Company. Any such bonus will be discretionary and will be subject to the terms of the applicable bonus program, the terms of which program may be modified from year to year in the sole discretion of the Company's Board of Directors.

(d) You will receive a grant of Cumberland Pharmaceuticals common stock, pursuant to a restricted stock agreement (RSA). Such shares will be subject to the RSA and the terms set forth in the incentive compensation plan under which they are awarded. You may, at the Company's sole discretion, receive additional awards of Company equity, which will be subject to their designated agreements and the incentive compensation plans under which they are awarded.

(e) Except as set forth in Section 2, the Company shall not be liable to you for any expense incurred by you unless you receive the Company's prior written consent to reimburse you for such expense.

2. Additional Payments. During the term hereof, you shall be entitled to receive prompt reimbursement for all reasonable and documented expenses incurred in the performance of services in accordance with the expense reimbursement policy of the Company. Such reimbursement policy shall require adequate documentation by you of the expenses and payment by the Company of such amounts shall be made within a reasonable period after the close of the year in which the expenses were incurred.

3. Employment at Will. This Agreement is not intended to and shall not be understood in any manner as affecting or modifying the at-will status of your employment with the Company. As an at-will employee either you or the Company may terminate the employment relationship at any time with or without cause or notice. The obligations of Sections 4, 5, 6, 7, 8, 10, 11 and 12 herein shall survive the termination of the employment relationship or of this Agreement.

4. Confidentiality. All knowledge and information, not already available to the public, which you acquire, have acquired, or will acquire in the course of your employment with the Company with respect to the Company's business, work methods, or pending regulatory matters, or other Company matters that are treated by the Company as confidential, shall be regarded by you as trade secrets, whether or not they are classifiable legally as trade secrets, and shall be treated by you as strictly confidential. Such knowledge and information shall not either directly or indirectly be used, disclosed, or made accessible to anyone by you for any purpose, except in the ordinary course of the Company's business under circumstances in which you are authorized to use or disclose such information. No disclosures of such confidential information shall be made outside of those you are authorized to make in the regular and ordinary course of your duties unless and until you receive prior written permission of the Board of Directors of the Company to make such disclosure.

5. Discoveries and Improvements. During the time that you are employed by the Company, all confidential information, trade secrets, or proprietary information and all other discoveries, inventions, software programs, processes, methods and improvements that are conceived, developed, or otherwise made by you , alone or with others, that relate in any way to the Company's present or planned business or products (collectively the 'Developments'), whether or not patentable or subject to copyright protection and whether or not reduced to tangible form or reduced to practice, shall be the sole property of the Company. You agree to disclose all Developments promptly, fully and in writing to the Company. You agree to keep and maintain adequate and current dated and witnessed written records of all such Developments, in the form of notes, sketches, drawings, or reports, which records shall be promptly submitted to the

Company and shall be and remain the property of the Company at all times. You agree to assign, and hereby do assign, to, the Company all your right, title and interest throughout the world in and to all Developments. You agree that all Developments shall constitute 'Works for Hire' (as such are defined under the U.S. Copyright Laws) and hereby assign to the Company all copyrights, patents and other proprietary rights you may have in any Developments without any obligation on the part of the Company to pay royalties or any other consideration to you for such Developments.

6. Publication. All documents and other writings produced by you during the period of your employment, which relate to work you are doing or have done for the Company or to the business of the Company or its affiliates, shall belong to the Company. You will not publish outside of the Company any such writing without the prior written consent of the Board of Directors of the Company. You will, without further compensation, execute at any time (whether or not you are still employed by the Company) all documents requested of you relating to the protection of such rights, including the assignment of such rights to the Company.

7. Litigation. You shall notify the Company within three business days if no longer employed and immediately if still employed by the Company if you are contacted by any person relating to any claim or litigation against the Company. You shall not communicate in any manner with any person related to any claim or litigation against the Company without the prior consent of the Board of Directors of the Company unless compelled to do so by law.

8. Competition. For so long as you are employed by the Company or any Affiliate (as defined below) and for a period of one year after you cease to be employed by the Company or any Affiliate, you shall not, directly or indirectly, engage in any work or other activity–whether as owner, stockholder, partner, officer, consultant, or otherwise–involving a trademark, product, or process that, in the opinion of the Company's Chief Executive Officer, is similar to a trademark, product or process on which you worked for the Company (or any Affiliate) or obtained knowledge about while working for the Company at any time during the period of employment, if such work or other activity is then, or reasonably expected to become, competitive with that of the Company (or any Affiliate). The restriction in the preceding sentence shall not apply if you have disclosed to the Company in writing all the known facts relating to such work or activity and have received a release in writing from the Board of Directors of the Company allowing you to engage in such work or activity. The Company's Chief Executive Officer shall have sole discretion to determine whether your work or activity for another employer involves trademarks, products, or processes that are similar to trademarks, products, or processes that you worked on for the Company. Ownership by you of five percent (5%) or less of the outstanding shares of stock of any company either (i) listed on a national securities exchange, or (ii) having at least one hundred (100) stockholders shall not make you a 'stockholder' within the meaning of that term as used in this paragraph. For one year after you cease to work for the Company, you will not engage in any work or activity that will cause you to inevitably disclose to anyone not employed by the Company (or an Affiliate) any trade secret or confidential information that belongs to the Company or one of its Affiliates. Nothing in this paragraph shall limit the rights or remedies of the Company arising, directly or indirectly, from such competitive employment, including, without limitation, claims based upon breach of

fiduciary duty, misappropriation, or theft of confidential information. The term 'Affiliate' shall mean the Company and any entity controlling, controlled by, or under common control with the Company.

9. Conflicting Contracts. You represent and warrant that you are not now under any obligation resulting from any contract or arrangement, to any person, firm, or corporation, which is inconsistent or in conflict with this Agreement. Likewise you represent and warrant that you are not now under any obligation resulting from any contract or arrangement to any person, firm, or corporation which would prevent, limit, or impair in any way the performance by you of your obligations to the Company.

10. Solicitation. After you cease to be employed by the Company (or a Company affiliate):

(a) You agree not to solicit, directly or indirectly, business related to the development or sales of pharmaceutical products from any entity, organization, or person which is contracted with the Company, which has been doing business with the Company or from which the Company was soliciting at the time of your termination, or a firm which you knew or had reason to know that the Company was going to solicit business at the time you ceased to be employed by the Company. The restriction set forth in the preceding sentence shall not apply if you have disclosed to the Company in writing all the known facts relating to such solicitation and have received a release in writing from the Board of Directors of the Company to engage in such solicitation.

(b) You agree not to solicit, recruit, hire, or assist in the hiring of any employee of the Company to work for you or another person, firm, corporation, or business.

11. Return of Documents. Upon termination of your employment for any reason, you shall immediately return to the Company all documents and things belonging to the Company. This includes, but is not limited to, trade secrets, confidential information, knowledge, data or know-how, and software containing such information, whether or not the documents are marked 'Confidential.'

12. Remedies. You acknowledge that in the event of breach of this Agreement by you, actual damages to the Company will be impossible to calculate, the Company's remedies at law will be inadequate, and the Company will suffer irreparable harm. Therefore, you agree that any of the covenants contained in this Agreement may be specifically enforced through injunctive relief, but such right to injunctive relief shall not preclude the Company from other remedies which may be available to it. You further agree that should you fail to keep any of the promises made by you in this Agreement, or any way violate this Agreement, the Company shall be entitled to recover all monies the Company is required to spend, including attorneys' fees, to enforce the provisions of this Agreement.

13. Best Efforts and Conflicts of Interest: You are hired with the understanding that Cumberland is your sole employer and you will provide a full-time work effort. You agree to devote your entire professional and business-related time and best efforts to the services required of you by the express and implicit terms of this Agreement, to the reasonable

satisfaction of Cumberland in its sole and complete discretion. Engaging in activities outside of work that create a conflict of interest, or detract from your ability to perform your assigned responsibilities or meet your defined goals and objectives with Cumberland, is a problem and may lead to disciplinary action up to and including termination of employment. If you believe that you are potentially involved in a situation that could create a conflict of interest and affect your ability to adequately perform your job with Cumberland, you should inform your direct supervisor and Cumberland's Human Resources Department immediately.

14. Standards of Business Conduct and Ethics.Cumberland's commitment to a culture of integrity, ethics and compliance with the law is comprised in this policy, which will be provided to you as part of the conditions of your employment. You will have the opportunity to read, discuss and understand this policy prior to accepting and signing its Letter of Agreement.

15. Debarment. You represent and warrant that you have not been debarred and will notify the Company immediately if you are debarred, pursuant to subsection 306(a) or 306(b) of the Federal Food, Drug, and Cosmetic Act.

16. Notice. Any notice required or permitted to be given under this Agreement shall be sufficient if in writing and if sent by registered or certified mail to your residence or to the Company's principal office in the case of the Company.

17 Waiver. The waiver by either party of any provision of this Agreement shall not operate or be construed as a waiver of any subsequent breach.

18. Entire Agreement. This Agreement contains the entire agreement of the parties and may not be changed orally, but only by an agreement in writing signed by the party against whom enforcement of any waiver, change, modification, extension, or discharge is sought.

19. Governance. This Agreement shall be governed by the laws of the State of Tennessee. Any dispute arising out of this Agreement shall be resolved, at the Company's sole option, by courts sitting in Nashville, Tennessee, and you waive any objection to such venue.

20. Enforceability. In the event that any provision of this Agreement shall be held by a court to be unenforceable, such provision will be enforced to the maximum extent permissible, and the remaining portions of this Agreement shall remain in full force and effect.

21. Survival. Notwithstanding any termination of your employment, this Agreement shall survive and remain in effect in accordance with its terms.

This letter agreement may be signed in one or more counterparts, each of which shall be an original and all of which will constitute one and the same instrument.

Mr. Martin E. Cearnal

Re: Employment of Martin E. Cearnal as Executive Vice President, Chief Commercial Officer by Cumberland Pharmaceuticals Inc.

Effective January 1, 2020, this letter agreement (the 'Agreement') will evidence the terms and conditions under which you will be employed by Cumberland Pharmaceuticals Inc. (the 'Company') In consideration of your appointment as Executive Vice President, Chief Commercial Officer of the Company, and other good and valuable consideration, the receipt and sufficiency of which is hereby acknowledged, the parties agree as follows:

1. Compensation.The Company agrees to compensate you as follows:

(a) The Company agrees to pay you on a salary basis for services performed based on an annual rate of three hundred twenty-five thousand dollars ($325,000.00), payable in arrears in equal monthly installments on the 25esimoday of each calendar month of 2020. For each year, thereafter, you will be paid on a salary basis for services performed based on an annual rate determined by the Company in its sole discretion; provided, however, that any obligation to make payments under this Section 1(a) will cease upon termination of your employment for any reason. Notwithstanding the foregoing, nothing in this Section 1(a) alters or is intended to alter the at-will nature of your employment as described in Section 3 of this Agreement.

(b) You will be eligible to participate in any Company-wide employee benefits as approved by the Board of Directors. The terms of your eligibility and participation will be governed by the provisions of the employee benefit plans, as such plans may be amended from time to time in the discretion of the Company's Board of Directors.

(c) You may be eligible for any Company bonus program, based upon performance in meeting your individual objectives and the Company's overall performance, both as determined and approved by the Board of Directors of the Company. Any such bonus will be discretionary and will be subject to the terms of the applicable bonus program, the terms of which program may be modified from year to year in the sole discretion of the Company's Board of Directors.

(d) You will receive a grant of Cumberland Pharmaceuticals common stock, pursuant to a restricted stock agreement (RSA). Such shares will be subject to the RSA and the terms set forth in the incentive compensation plan under which they are awarded. You may, at the Company's sole discretion, receive additional awards of Company equity, which will be subject to their designated agreements and the incentive compensation plans under which they are awarded.

(e) Except as set forth in Section 2, the Company shall not be liable to you for any expense incurred by you unless you receive the Company's prior written consent to reimburse you for such expense.

1.Additional Payments. During the term hereof, you shall be entitled to receive prompt reimbursement for all reasonable and documented expenses incurred in the performance of services in accordance with the expense reimbursement policy of the Company. Such reimbursement policy shall require adequate documentation by you of the expenses and payment by the Company of such amounts shall be made within a reasonable period after the close of the year in which the expenses were incurred.

3. Employment at Will. This Agreement is not intended to and shall not be understood in any manner as affecting or modifying the at-will status of your employment with the Company. As an at-will employee either you or the Company may terminate the employment relationship at any time with or without cause or notice. The obligations of Sections 4, 5, 6, 7, 8, 10, 11 and 12 herein shall survive the termination of the employment relationship or of this Agreement.

4. Confidentiality. All knowledge and information, not already available to the public, which you acquire, have acquired, or will acquire in the course of your employment with the Company with respect to the Company's business, work methods, or pending regulatory matters, or other Company matters that are treated by the Company as confidential, shall be regarded by you as trade secrets, whether or not they are classifiable legally as trade secrets, and shall be treated by you as strictly confidential. Such knowledge and information shall not either directly or indirectly be used, disclosed, or made accessible to anyone by you for any purpose, except in the ordinary course of the Company's business under circumstances in which you are authorized to use or disclose such information. No disclosures of such confidential information shall be made outside of those you are authorized to make in the regular and ordinary course of your duties unless and until you receive prior written permission of the Board of Directors of the Company to make such disclosure.

5. Discoveries and Improvements. During the time that you are employed by the Company, all confidential information, trade secrets, or proprietary information and all other discoveries, inventions, software programs, processes, methods and improvements that are conceived, developed, or otherwise made by you , alone or with others, that relate in any way to the Company's present or planned business or products (collectively the 'Developments'), whether or not patentable or subject to copyright protection and whether or not reduced to tangible form or reduced to practice, shall be the sole property of the Company. You agree to disclose all Developments promptly, fully and in writing to the Company. You agree to keep and maintain adequate and current dated and witnessed written records of all such Developments, in the form

of notes, sketches, drawings, or reports, which records shall be promptly submitted to the Company and shall be and remain the property of the Company at all times. You agree to assign, and hereby do assign, to, the Company all your right, title and interest throughout the world in and to all Developments. You agree that all Developments shall constitute 'Works for Hire' (as such are defined under the U.S. Copyright Laws) and hereby assign to the Company all copyrights, patents and other proprietary rights you may have in any Developments without any obligation on the part of the Company to pay royalties or any other consideration to you for such Developments.

6. Publication. All documents and other writings produced by you during the period of your employment, which relate to work you are doing or have done for the Company or to the business of the Company or its affiliates, shall belong to the Company. You will not publish outside of the Company any such writing without the prior written consent of the Board of Directors of the Company. You will, without further compensation, execute at any time (whether or not you are still employed by the Company) all documents requested of you relating to the protection of such rights, including the assignment of such rights to the Company.

7. Litigation. You shall notify the Company within three business days if no longer employed and immediately if still employed by the Company if you are contacted by any person relating to any claim or litigation against the Company. You shall not communicate in any manner with any person related to any claim or litigation against the Company without the prior consent of the Board of Directors of the Company unless compelled to do so by law.

8. Competition. For so long as you are employed by the Company or any Affiliate (as defined below) and for a period of one year after you cease to be employed by the Company or any Affiliate, you shall not, directly or indirectly, engage in any work or other activity–whether as owner, stockholder, partner, officer, consultant, or otherwise–involving a trademark, product, or process that, in the opinion of the Company's Chief Executive Officer, is similar to a trademark, product or process on which you worked for the Company (or any Affiliate) or obtained knowledge about while working for the Company at any time during the period of employment, if such work or other activity is then, or reasonably expected to become, competitive with that of the Company (or any Affiliate). The restriction in the preceding sentence shall not apply if you have disclosed to the Company in writing all the known facts relating to such work or activity and have received a release in writing from the Board of Directors of the Company allowing you to engage in such work or activity. The Company's Chief Executive Officer shall have sole discretion to determine whether your work or activity for another employer involves trademarks, products, or processes that are similar to trademarks, products, or processes that you worked on for the Company. Ownership by you of five percent (5%) or less of the outstanding shares of stock of any company either (i) listed on a national securities exchange, or (ii) having at least one hundred (100) stockholders shall not make you a 'stockholder' within the meaning of that term as used in this paragraph. For one year after you cease to work for the Company, you will not engage in any work or activity that will cause you to inevitably disclose to anyone not employed by the Company (or an Affiliate) any trade secret or confidential information that belongs to the Company or one of its Affiliates. Nothing in this paragraph shall limit the rights or remedies of the Company arising, directly or indirectly, from

such competitive employment, including, without limitation, claims based upon breach of fiduciary duty, misappropriation, or theft of confidential information. The term 'Affiliate' shall mean the Company and any entity controlling, controlled by, or under common control with the Company.

9. Conflicting Contracts. You represent and warrant that you are not now under any obligation resulting from any contract or arrangement, to any person, firm, or corporation, which is inconsistent or in conflict with this Agreement. Likewise you represent and warrant that you are not now under any obligation resulting from any contract or arrangement to any person, firm, or corporation which would prevent, limit, or impair in any way the performance by you of your obligations to the Company.

10. Solicitation. After you cease to be employed by the Company (or a Company affiliate):

(a) You agree not to solicit, directly or indirectly, business related to the development or sales of pharmaceutical products from any entity, organization, or person which is contracted with the Company, which has been doing business with the Company or from which the Company was soliciting at the time of your termination, or a firm which you knew or had reason to know that the Company was going to solicit business at the time you ceased to be employed by the Company. The restriction set forth in the preceding sentence shall not apply if you have disclosed to the Company in writing all the known facts relating to such solicitation and have received a release in writing from the Board of Directors of the Company to engage in such solicitation.

(b) You agree not to solicit, recruit, hire, or assist in the hiring of any employee of the Company to work for you or another person, firm, corporation, or business.

11. Return of Documents. Upon termination of your employment for any reason, you shall immediately return to the Company all documents and things belonging to the Company. This includes, but is not limited to, trade secrets, confidential information, knowledge, data or know-how, and software containing such information, whether or not the documents are marked 'Confidential.'

12. Remedies. You acknowledge that in the event of breach of this Agreement by you, actual damages to the Company will be impossible to calculate, the Company's remedies at law will be inadequate, and the Company will suffer irreparable harm. Therefore, you agree that any of the covenants contained in this Agreement may be specifically enforced through injunctive relief, but such right to injunctive relief shall not preclude the Company from other remedies which may be available to it. You further agree that should you fail to keep any of the promises made by you in this Agreement, or any way violate this Agreement, the Company shall be entitled to recover all monies the Company is required to spend, including attorneys' fees, to enforce the provisions of this Agreement.

13. Best Efforts and Conflicts of Interest: You are hired with the understanding that Cumberland is your sole employer and you will provide a full-time work effort. You agree to devote your entire professional and business-related time and best efforts to the services

required of you by the express and implicit terms of this Agreement, to the reasonable satisfaction of Cumberland in its sole and complete discretion. Engaging in activities outside of work that create a conflict of interest, or detract from your ability to perform your assigned responsibilities or meet your defined goals and objectives with Cumberland, is a problem and may lead to disciplinary action up to and including termination of employment. If you believe that you are potentially involved in a situation that could create a conflict of interest and affect your ability to adequately perform your job with Cumberland, you should inform your direct supervisor and Cumberland's Human Resources Department immediately.

14. Standards of Business Conduct and Ethics.Cumberland's commitment to a culture of integrity, ethics and compliance with the law is comprised in this policy, which will be provided to you as part of the conditions of your employment. You will have the opportunity to read, discuss and understand this policy prior to accepting and signing its Letter of Agreement.

15. Debarment. You represent and warrant that you have not been debarred and will notify the Company immediately if you are debarred, pursuant to subsection 306(a) or 306(b) of the Federal Food, Drug, and Cosmetic Act.

16. Notice. Any notice required or permitted to be given under this Agreement shall be sufficient if in writing and if sent by registered or certified mail to your residence or to the Company's principal office in the case of the Company.

17 Waiver. The waiver by either party of any provision of this Agreement shall not operate or be construed as a waiver of any subsequent breach.

18. Entire Agreement. This Agreement contains the entire agreement of the parties and may not be changed orally, but only by an agreement in writing signed by the party against whom enforcement of any waiver, change, modification, extension, or discharge is sought.

19. Governance. This Agreement shall be governed by the laws of the State of Tennessee. Any dispute arising out of this Agreement shall be resolved, at the Company's sole option, by courts sitting in Nashville, Tennessee, and you waive any objection to such venue.

20. Enforceability. In the event that any provision of this Agreement shall be held by a court to be unenforceable, such provision will be enforced to the maximum extent permissible, and the remaining portions of this Agreement shall remain in full force and effect.

21. Survival. Notwithstanding any termination of your employment, this Agreement shall survive and remain in effect in accordance with its terms.

This letter agreement may be signed in one or more counterparts, each of which shall be an original and all of which will constitute one and the same instrument.

Mr. Leo Pavliv

Re: Employment of Leo Pavliv as Executive Vice President, Operations and Chief Development Officer by Cumberland Pharmaceuticals Inc.

Effective January 1, 2020, this letter agreement (the 'Agreement') will evidence the terms and conditions under which you will be employed by Cumberland Pharmaceuticals Inc. (the 'Company') In consideration of your appointment as Executive Vice President, Operations and Chief Development Officer of the Company, and other good and valuable consideration, the receipt and sufficiency of which is hereby acknowledged, the parties agree as follows:

1. Compensation.The Company agrees to compensate you as follows:

(a) The Company agrees to pay you on a salary basis for services performed based on an annual rate of four hundred twenty-two thousand dollars ($422,000.00), payable in arrears in equal monthly installments on the 25esimoday of each calendar month of 2020. For each year, thereafter, you will be paid on a salary basis for services performed based on an annual rate determined by the Company in its sole discretion; provided, however, that any obligation to make payments under this Section 1(a) will cease upon termination of your employment for any reason. Notwithstanding the foregoing, nothing in this Section 1(a) alters or is intended to alter the at-will nature of your employment as described in Section 3 of this Agreement.

(b) You will be eligible to participate in any Company-wide employee benefits as approved by the Board of Directors. The terms of your eligibility and participation will be governed by the provisions of the employee benefit plans, as such plans may be amended from time to time in the discretion of the Company's Board of Directors.

(c) You may be eligible for any Company bonus program, based upon performance in meeting your individual objectives and the Company's overall performance, both as determined and approved by the Board of Directors of the Company. Any such bonus will be discretionary

and will be subject to the terms of the applicable bonus program, the terms of which program may be modified from year to year in the sole discretion of the Company's Board of Directors.

(d) You will receive a grant of Cumberland Pharmaceuticals common stock, pursuant to a restricted stock agreement (RSA). Such shares will be subject to the RSA and the terms set forth in the incentive compensation plan under which they are awarded. You may, at the Company's sole discretion, receive additional awards of Company equity, which will be subject to their designated agreements and the incentive compensation plans under which they are awarded.

(e) Except as set forth in Section 2, the Company shall not be liable to you for any expense incurred by you unless you receive the Company's prior written consent to reimburse you for such expense.

2. Additional Payments. During the term hereof, you shall be entitled to receive prompt reimbursement for all reasonable and documented expenses incurred in the performance of services in accordance with the expense reimbursement policy of the Company. Such reimbursement policy shall require adequate documentation by you of the expenses and payment by the Company of such amounts shall be made within a reasonable period after the close of the year in which the expenses were incurred.

3. Employment at Will. This Agreement is not intended to and shall not be understood in any manner as affecting or modifying the at-will status of your employment with the Company. As an at-will employee either you or the Company may terminate the employment relationship at any time with or without cause or notice. The obligations of Sections 4, 5, 6, 7, 8, 10, 11 and 12 herein shall survive the termination of the employment relationship or of this Agreement.

4. Confidentiality. All knowledge and information, not already available to the public, which you acquire, have acquired, or will acquire in the course of your employment with the Company with respect to the Company's business, work methods, or pending regulatory matters, or other Company matters that are treated by the Company as confidential, shall be regarded by you as trade secrets, whether or not they are classifiable legally as trade secrets, and shall be treated by you as strictly confidential. Such knowledge and information shall not either directly or indirectly be used, disclosed, or made accessible to anyone by you for any purpose, except in the ordinary course of the Company's business under circumstances in which you are authorized to use or disclose such information. No disclosures of such confidential information shall be made outside of those you are authorized to make in the regular and ordinary course of your duties unless and until you receive prior written permission of the Board of Directors of the Company to make such disclosure.

5. Discoveries and Improvements. During the time that you are employed by the Company, all confidential information, trade secrets, or proprietary information and all other discoveries, inventions, software programs, processes, methods and improvements that are conceived, developed, or otherwise made by you , alone or with others, that relate in any way to the Company's present or planned business or products (collectively the 'Developments'), whether or not patentable or subject to copyright protection and whether or not reduced to tangible form or reduced to practice, shall be the sole property of the Company. You agree to disclose all

Developments promptly, fully and in writing to the Company. You agree to keep and maintain adequate and current dated and witnessed written records of all such Developments, in the form of notes, sketches, drawings, or reports, which records shall be promptly submitted to the Company and shall be and remain the property of the Company at all times. You agree to assign, and hereby do assign, to, the Company all your right, title and interest throughout the world in and to all Developments. You agree that all Developments shall constitute 'Works for Hire' (as such are defined under the U.S. Copyright Laws) and hereby assign to the Company all copyrights, patents and other proprietary rights you may have in any Developments without any obligation on the part of the Company to pay royalties or any other consideration to you for such Developments.

6. Publication. All documents and other writings produced by you during the period of your employment, which relate to work you are doing or have done for the Company or to the business of the Company or its affiliates, shall belong to the Company. You will not publish outside of the Company any such writing without the prior written consent of the Board of Directors of the Company. You will, without further compensation, execute at any time (whether or not you are still employed by the Company) all documents requested of you relating to the protection of such rights, including the assignment of such rights to the Company.

7. Litigation. You shall notify the Company within three business days if no longer employed and immediately if still employed by the Company if you are contacted by any person relating to any claim or litigation against the Company. You shall not communicate in any manner with any person related to any claim or litigation against the Company without the prior consent of the Board of Directors of the Company unless compelled to do so by law.

8. Competition. For so long as you are employed by the Company or any Affiliate (as defined below) and for a period of one year after you cease to be employed by the Company or any Affiliate, you shall not, directly or indirectly, engage in any work or other activity–whether as owner, stockholder, partner, officer, consultant, or otherwise–involving a trademark, product, or process that, in the opinion of the Company's Chief Executive Officer, is similar to a trademark, product or process on which you worked for the Company (or any Affiliate) or obtained knowledge about while working for the Company at any time during the period of employment, if such work or other activity is then, or reasonably expected to become, competitive with that of the Company (or any Affiliate). The restriction in the preceding sentence shall not apply if you have disclosed to the Company in writing all the known facts relating to such work or activity and have received a release in writing from the Board of Directors of the Company allowing you to engage in such work or activity. The Company's Chief Executive Officer shall have sole discretion to determine whether your work or activity for another employer involves trademarks, products, or processes that are similar to trademarks, products, or processes that you worked on for the Company. Ownership by you of five percent (5%) or less of the outstanding shares of stock of any company either (i) listed on a national securities exchange, or (ii) having at least one hundred (100) stockholders shall not make you a 'stockholder' within the meaning of that term as used in this paragraph. For one year after you cease to work for the Company, you will not engage in any work or activity that will cause you to inevitably disclose to anyone not employed by the Company (or an Affiliate) any trade secret

or confidential information that belongs to the Company or one of its Affiliates. Nothing in this paragraph shall limit the rights or remedies of the Company arising, directly or indirectly, from such competitive employment, including, without limitation, claims based upon breach of fiduciary duty, misappropriation, or theft of confidential information. The term 'Affiliate' shall mean the Company and any entity controlling, controlled by, or under common control with the Company.

9. Conflicting Contracts. You represent and warrant that you are not now under any obligation resulting from any contract or arrangement, to any person, firm, or corporation, which is inconsistent or in conflict with this Agreement. Likewise you represent and warrant that you are not now under any obligation resulting from any contract or arrangement to any person, firm, or corporation which would prevent, limit, or impair in any way the performance by you of your obligations to the Company.

10. Solicitation. After you cease to be employed by the Company (or a Company affiliate):

(a) You agree not to solicit, directly or indirectly, business related to the development or sales of pharmaceutical products from any entity, organization, or person which is contracted with the Company, which has been doing business with the Company or from which the Company was soliciting at the time of your termination, or a firm which you knew or had reason to know that the Company was going to solicit business at the time you ceased to be employed by the Company. The restriction set forth in the preceding sentence shall not apply if you have disclosed to the Company in writing all the known facts relating to such solicitation and have received a release in writing from the Board of Directors of the Company to engage in such solicitation.

(b) You agree not to solicit, recruit, hire, or assist in the hiring of any employee of the Company to work for you or another person, firm, corporation, or business.

11. Return of Documents. Upon termination of your employment for any reason, you shall immediately return to the Company all documents and things belonging to the Company. This includes, but is not limited to, trade secrets, confidential information, knowledge, data or know-how, and software containing such information, whether or not the documents are marked 'Confidential.'

12. Remedies. You acknowledge that in the event of breach of this Agreement by you, actual damages to the Company will be impossible to calculate, the Company's remedies at law will be inadequate, and the Company will suffer irreparable harm. Therefore, you agree that any of the covenants contained in this Agreement may be specifically enforced through injunctive relief, but such right to injunctive relief shall not preclude the Company from other remedies which may be available to it. You further agree that should you fail to keep any of the promises made by you in this Agreement, or any way violate this Agreement, the Company shall be entitled to recover all monies the Company is required to spend, including attorneys' fees, to enforce the provisions of this Agreement.

13. Best Efforts and Conflicts of Interest: You are hired with the understanding that

Cumberland is your sole employer and you will provide a full-time work effort. You agree to devote your entire professional and business-related time and best efforts to the services required of you by the express and implicit terms of this Agreement, to the reasonable satisfaction of Cumberland in its sole and complete discretion. Engaging in activities outside of work that create a conflict of interest, or detract from your ability to perform your assigned responsibilities or meet your defined goals and objectives with Cumberland, is a problem and may lead to disciplinary action up to and including termination of employment. If you believe that you are potentially involved in a situation that could create a conflict of interest and affect your ability to adequately perform your job with Cumberland, you should inform your direct supervisor and Cumberland's Human Resources Department immediately.

14. Standards of Business Conduct and Ethics.Cumberland's commitment to a culture of integrity, ethics and compliance with the law is comprised in this policy, which will be provided to you as part of the conditions of your employment. You will have the opportunity to read, discuss and understand this policy prior to accepting and signing its Letter of Agreement.

15. Debarment. You represent and warrant that you have not been debarred and will notify the Company immediately if you are debarred, pursuant to subsection 306(a) or 306(b) of the Federal Food, Drug, and Cosmetic Act.

16. Notice. Any notice required or permitted to be given under this Agreement shall be sufficient if in writing and if sent by registered or certified mail to your residence or to the Company's principal office in the case of the Company.

17 Waiver. The waiver by either party of any provision of this Agreement shall not operate or be construed as a waiver of any subsequent breach.

18. Entire Agreement. This Agreement contains the entire agreement of the parties and may not be changed orally, but only by an agreement in writing signed by the party against whom enforcement of any waiver, change, modification, extension, or discharge is sought.

19. Governance. This Agreement shall be governed by the laws of the State of Tennessee. Any dispute arising out of this Agreement shall be resolved, at the Company's sole option, by courts sitting in Nashville, Tennessee, and you waive any objection to such venue.

20. Enforceability. In the event that any provision of this Agreement shall be held by a court to be unenforceable, such provision will be enforced to the maximum extent permissible, and the remaining portions of this Agreement shall remain in full force and effect.

21. Survival. Notwithstanding any termination of your employment, this Agreement shall survive and remain in effect in accordance with its terms.

This letter agreement may be signed in one or more counterparts, each of which shall be an original and all of which will constitute one and the same instrument.

Mr. Michael Bonner

Re: Employment of Michael Bonner as Senior Director, Finance & Accounting; Chief Financial Officer by Cumberland Pharmaceuticals Inc.

Effective January 1, 2020, this letter agreement (the 'Agreement') will evidence the terms and conditions under which you will be employed by Cumberland Pharmaceuticals Inc. (the 'Company') In consideration of your appointment as Senior Director, Finance & Accounting; Chief Financial Officer of the Company, and other good and valuable consideration, the receipt and sufficiency of which is hereby acknowledged, the parties agree as follows:

1. Compensation.The Company agrees to compensate you as follows:

(a) The Company agrees to pay you on a salary basis for services performed based on an annual rate of two hundred five thousand five hundred dollars ($205,500.00), payable in arrears in equal monthly installments on the 25esimoday of each calendar month of 2020. For each year, thereafter, you will be paid on a salary basis for services performed based on an annual rate determined by the Company in its sole discretion; provided, however, that any obligation to make payments under this Section 1(a) will cease upon termination of your employment for any reason. Notwithstanding the foregoing, nothing in this Section 1(a) alters or is intended to alter the at-will nature of your employment as described in Section 3 of this Agreement.

(b) You will be eligible to participate in any Company-wide employee benefits as approved by the Board of Directors. The terms of your eligibility and participation will be governed by the provisions of the employee benefit plans, as such plans may be amended from time to time in the discretion of the Company's Board of Directors.

(c) You may be eligible for any Company bonus program, based upon performance in meeting your individual objectives and the Company's overall performance, both as determined and approved by the Board of Directors of the Company. Any such bonus will be discretionary

and will be subject to the terms of the applicable bonus program, the terms of which program may be modified from year to year in the sole discretion of the Company's Board of Directors.

(d) You will receive a grant of Cumberland Pharmaceuticals common stock, pursuant to a restricted stock agreement (RSA). Such shares will be subject to the RSA and the terms set forth in the incentive compensation plan under which they are awarded. You may, at the Company's sole discretion, receive additional awards of Company equity, which will be subject to their designated agreements and the incentive compensation plans under which they are awarded.

(e) Except as set forth in Section 2, the Company shall not be liable to you for any expense incurred by you unless you receive the Company's prior written consent to reimburse you for such expense.

2. Additional Payments. During the term hereof, you shall be entitled to receive prompt reimbursement for all reasonable and documented expenses incurred in the performance of services in accordance with the expense reimbursement policy of the Company. Such reimbursement policy shall require adequate documentation by you of the expenses and payment by the Company of such amounts shall be made within a reasonable period after the close of the year in which the expenses were incurred.

3. Employment at Will. This Agreement is not intended to and shall not be understood in any manner as affecting or modifying the at-will status of your employment with the Company. As an at-will employee either you or the Company may terminate the employment relationship at any time with or without cause or notice. The obligations of Sections 4, 5, 6, 7, 8, 10, 11 and 12 herein shall survive the termination of the employment relationship or of this Agreement.

4. Confidentiality. All knowledge and information, not already available to the public, which you acquire, have acquired, or will acquire in the course of your employment with the Company with respect to the Company's business, work methods, or pending regulatory matters, or other Company matters that are treated by the Company as confidential, shall be regarded by you as trade secrets, whether or not they are classifiable legally as trade secrets, and shall be treated by you as strictly confidential. Such knowledge and information shall not either directly or indirectly be used, disclosed, or made accessible to anyone by you for any purpose, except in the ordinary course of the Company's business under circumstances in which you are authorized to use or disclose such information. No disclosures of such confidential information shall be made outside of those you are authorized to make in the regular and ordinary course of your duties unless and until you receive prior written permission of the Board of Directors of the Company to make such disclosure.

5. Discoveries and Improvements. During the time that you are employed by the Company, all confidential information, trade secrets, or proprietary information and all other discoveries, inventions, software programs, processes, methods and improvements that are conceived, developed, or otherwise made by you , alone or with others, that relate in any way to the Company's present or planned business or products (collectively the 'Developments'), whether or not patentable or subject to copyright protection and whether or not reduced to tangible form or reduced to practice, shall be the sole property of the Company. You agree to disclose all

Developments promptly, fully and in writing to the Company. You agree to keep and maintain adequate and current dated and witnessed written records of all such Developments, in the form of notes, sketches, drawings, or reports, which records shall be promptly submitted to the Company and shall be and remain the property of the Company at all times. You agree to assign, and hereby do assign, to, the Company all your right, title and interest throughout the world in and to all Developments. You agree that all Developments shall constitute 'Works for Hire' (as such are defined under the U.S. Copyright Laws) and hereby assign to the Company all copyrights, patents and other proprietary rights you may have in any Developments without any obligation on the part of the Company to pay royalties or any other consideration to you for such Developments.

6. Publication. All documents and other writings produced by you during the period of your employment, which relate to work you are doing or have done for the Company or to the business of the Company or its affiliates, shall belong to the Company. You will not publish outside of the Company any such writing without the prior written consent of the Board of Directors of the Company. You will, without further compensation, execute at any time (whether or not you are still employed by the Company) all documents requested of you relating to the protection of such rights, including the assignment of such rights to the Company.

7. Litigation. You shall notify the Company within three business days if no longer employed and immediately if still employed by the Company if you are contacted by any person relating to any claim or litigation against the Company. You shall not communicate in any manner with any person related to any claim or litigation against the Company without the prior consent of the Board of Directors of the Company unless compelled to do so by law.

8. Competition. For so long as you are employed by the Company or any Affiliate (as defined below) and for a period of one year after you cease to be employed by the Company or any Affiliate, you shall not, directly or indirectly, engage in any work or other activity–whether as owner, stockholder, partner, officer, consultant, or otherwise–involving a trademark, product, or process that, in the opinion of the Company's Chief Executive Officer, is similar to a trademark, product or process on which you worked for the Company (or any Affiliate) or obtained knowledge about while working for the Company at any time during the period of employment, if such work or other activity is then, or reasonably expected to become, competitive with that of the Company (or any Affiliate). The restriction in the preceding sentence shall not apply if you have disclosed to the Company in writing all the known facts relating to such work or activity and have received a release in writing from the Board of Directors of the Company allowing you to engage in such work or activity. The Company's Chief Executive Officer shall have sole discretion to determine whether your work or activity for another employer involves trademarks, products, or processes that are similar to trademarks, products, or processes that you worked on for the Company. Ownership by you of five percent (5%) or less of the outstanding shares of stock of any company either (i) listed on a national securities exchange, or (ii) having at least one hundred (100) stockholders shall not make you a 'stockholder' within the meaning of that term as used in this paragraph. For one year after you cease to work for the Company, you will not engage in any work or activity that will cause you 1to inevitably disclose to anyone not employed by the Company (or an Affiliate) any trade secret

or confidential information that belongs to the Company or one of its Affiliates. Nothing in this paragraph shall limit the rights or remedies of the Company arising, directly or indirectly, from such competitive employment, including, without limitation, claims based upon breach of fiduciary duty, misappropriation, or theft of confidential information. The term 'Affiliate' shall mean the Company and any entity controlling, controlled by, or under common control with the Company.

9. Conflicting Contracts. You represent and warrant that you are not now under any obligation resulting from any contract or arrangement, to any person, firm, or corporation, which is inconsistent or in conflict with this Agreement. Likewise you represent and warrant that you are not now under any obligation resulting from any contract or arrangement to any person, firm, or corporation which would prevent, limit, or impair in any way the performance by you of your obligations to the Company.

10. Solicitation. After you cease to be employed by the Company (or a Company affiliate):

(a) You agree not to solicit, directly or indirectly, business related to the development or sales of pharmaceutical products from any entity, organization, or person which is contracted with the Company, which has been doing business with the Company or from which the Company was soliciting at the time of your termination, or a firm which you knew or had reason to know that the Company was going to solicit business at the time you ceased to be employed by the Company. The restriction set forth in the preceding sentence shall not apply if you have disclosed to the Company in writing all the known facts relating to such solicitation and have received a release in writing from the Board of Directors of the Company to engage in such solicitation.

(b) You agree not to solicit, recruit, hire, or assist in the hiring of any employee of the Company to work for you or another person, firm, corporation, or business.

11. Return of Documents. Upon termination of your employment for any reason, you shall immediately return to the Company all documents and things belonging to the Company. This includes, but is not limited to, trade secrets, confidential information, knowledge, data or know-how, and software containing such information, whether or not the documents are marked 'Confidential.'

12. Remedies. You acknowledge that in the event of breach of this Agreement by you, actual damages to the Company will be impossible to calculate, the Company's remedies at law will be inadequate, and the Company will suffer irreparable harm. Therefore, you agree that any of the covenants contained in this Agreement may be specifically enforced through injunctive relief, but such right to injunctive relief shall not preclude the Company from other remedies which may be available to it. You further agree that should you fail to keep any of the promises made by you in this Agreement, or any way violate this Agreement, the Company shall be entitled to recover all monies the Company is required to spend, including attorneys' fees, to enforce the provisions of this Agreement.

13. Best Efforts and Conflicts of Interest: You are hired with the understanding that

Cumberland is your sole employer and you will provide a full-time work effort. You agree to devote your entire professional and business-related time and best efforts to the services required of you by the express and implicit terms of this Agreement, to the reasonable satisfaction of Cumberland in its sole and complete discretion. Engaging in activities outside of work that create a conflict of interest, or detract from your ability to perform your assigned responsibilities or meet your defined goals and objectives with Cumberland, is a problem and may lead to disciplinary action up to and including termination of employment. If you believe that you are potentially involved in a situation that could create a conflict of interest and affect your ability to adequately perform your job with Cumberland, you should inform your direct supervisor and Cumberland's Human Resources Department immediately.

14. Standards of Business Conduct and Ethics.Cumberland's commitment to a culture of integrity, ethics and compliance with the law is comprised in this policy, which will be provided to you as part of the conditions of your employment. You will have the opportunity to read, discuss and understand this policy prior to accepting and signing its Letter of Agreement.

15. Debarment. You represent and warrant that you have not been debarred and will notify the Company immediately if you are debarred, pursuant to subsection 306(a) or 306(b) of the Federal Food, Drug, and Cosmetic Act.

16. Notice. Any notice required or permitted to be given under this Agreement shall be sufficient if in writing and if sent by registered or certified mail to your residence or to the Company's principal office in the case of the Company.

17 Waiver. The waiver by either party of any provision of this Agreement shall not operate or be construed as a waiver of any subsequent breach.

18. Entire Agreement. This Agreement contains the entire agreement of the parties and may not be changed orally, but only by an agreement in writing signed by the party against whom enforcement of any waiver, change, modification, extension, or discharge is sought.

19. Governance. This Agreement shall be governed by the laws of the State of Tennessee. Any dispute arising out of this Agreement shall be resolved, at the Company's sole option, by courts sitting in Nashville, Tennessee, and you waive any objection to such venue.

20. Enforceability. In the event that any provision of this Agreement shall be held by a court to be unenforceable, such provision will be enforced to the maximum extent permissible, and the remaining portions of this Agreement shall remain in full force and effect.

21. Survival. Notwithstanding any termination of your employment, this Agreement shall survive and remain in effect in accordance with its terms.

This letter agreement may be signed in one or more counterparts, each of which shall be an original and all of which will constitute one and the same instrument.

Mr. James L. Herman

Re: Employment of James L. Herman as Senior Vice President, National Accounts and Chief Compliance Officer by Cumberland Pharmaceuticals Inc.

Effective January 1, 2020, this letter agreement (the 'Agreement') will evidence the terms and conditions under which you will be employed by Cumberland Pharmaceuticals Inc. (the 'Company') In consideration of your appointment as Senior Vice President, National Accounts and Chief Compliance Officer of the Company, and other good and valuable consideration, the receipt and sufficiency of which is hereby acknowledged, the parties agree as follows:

1. Compensation.The Company agrees to compensate you as follows:

(a) The Company agrees to pay you on a salary basis for services performed based on an annual rate of two hundred sixty thousand dollars ($260,000.00), payable in arrears in equal monthly installments on the 25esimoday of each calendar month of 2020. For each year, thereafter, you will be paid on a salary basis for services performed based on an annual rate determined by the Company in its sole discretion; provided, however, that any obligation to make payments under this Section 1(a) will cease upon termination of your employment for any reason. Notwithstanding the foregoing, nothing in this Section 1(a) alters or is intended to alter the at-will nature of your employment as described in Section 3 of this Agreement.

(b) You will be eligible to participate in any Company-wide employee benefits as approved by the Board of Directors. The terms of your eligibility and participation will be governed by the provisions of the employee benefit plans, as such plans may be amended from time to time in the discretion of the Company's Board of Directors.

(c) You may be eligible for any Company bonus program, based upon performance in meeting your individual objectives and the Company's overall performance, both as determined and approved by the Board of Directors of the Company. Any such bonus will be discretionary and will be subject to the terms of the applicable bonus program, the terms of which program may be modified from year to year in the sole discretion of the Company's Board of Directors.

(d) You will receive a grant of Cumberland Pharmaceuticals common stock, pursuant to a restricted stock agreement (RSA). Such shares will be subject to the RSA and the terms set forth in the incentive compensation plan under which they are awarded. You may, at the Company's sole discretion, receive additional awards of Company equity, which will be subject to their designated agreements and the incentive compensation plans under which they are awarded.

(e) Except as set forth in Section 2, the Company shall not be liable to you for any expense incurred by you unless you receive the Company's prior written consent to reimburse you for such expense.

2. Additional Payments. During the term hereof, you shall be entitled to receive prompt reimbursement for all reasonable and documented expenses incurred in the performance of services in accordance with the expense reimbursement policy of the Company. Such reimbursement policy shall require adequate documentation by you of the expenses and payment by the Company of such amounts shall be made within a reasonable period after the close of the year in which the expenses were incurred.

3. Employment at Will. This Agreement is not intended to and shall not be understood in any manner as affecting or modifying the at-will status of your employment with the Company. As an at-will employee either you or the Company may terminate the employment relationship at any time with or without cause or notice. The obligations of Sections 4, 5, 6, 7, 8, 10, 11 and 12 herein shall survive the termination of the employment relationship or of this Agreement.

4. Confidentiality. All knowledge and information, not already available to the public, which you acquire, have acquired, or will acquire in the course of your employment with the Company with respect to the Company's business, work methods, or pending regulatory matters, or other Company matters that are treated by the Company as confidential, shall be regarded by you as trade secrets, whether or not they are classifiable legally as trade secrets, and shall be treated by you as strictly confidential. Such knowledge and information shall not either directly or indirectly be used, disclosed, or made accessible to anyone by you for any purpose, except in the ordinary course of the Company's business under circumstances in which you are authorized to use or disclose such information. No disclosures of such confidential information shall be made outside of those you are authorized to make in the regular and ordinary course of your duties unless and until you receive prior written permission of the Board of Directors of the Company to make such disclosure.

5. Discoveries and Improvements. During the time that you are employed by the Company, all confidential information, trade secrets, or proprietary information and all other discoveries, inventions, software programs, processes, methods and improvements that are conceived, developed, or otherwise made by you , alone or with others, that relate in any way to the Company's present or planned business or products (collectively the 'Developments'), whether or not patentable or subject to copyright protection and whether or not reduced to tangible form or reduced to practice, shall be the sole property of the Company. You agree to disclose all Developments promptly, fully and in writing to the Company. You agree to keep and maintain adequate and current dated and witnessed written records of all such Developments, in the form of notes, sketches, drawings, or reports, which records shall be promptly submitted to the Company and shall be and remain the property of the Company at all times. You agree to assign, and hereby do assign, to, the Company all your right, title and interest throughout the world in and to all Developments. You agree that all Developments shall constitute 'Works for Hire' (as such are defined under the U.S. Copyright Laws) and hereby assign to the Company all copyrights, patents and other proprietary rights you may have in any Developments without any obligation on the part of the Company to pay royalties or any other consideration to you for such Developments.

6. Publication. All documents and other writings produced by you during the period of your employment, which relate to work you are doing or have done for the Company or to the business of the Company or its affiliates, shall belong to the Company. You will not publish outside of the Company any such writing without the prior written consent of the Board of Directors of the Company. You will, without further compensation, execute at any time (whether or not you are still employed by the Company) all documents requested of you relating to the protection of such rights, including the assignment of such rights to the Company.

7. Litigation. You shall notify the Company within three business days if no longer employed and immediately if still employed by the Company if you are contacted by any person relating to any claim or litigation against the Company. You shall not communicate in any manner with any person related to any claim or litigation against the Company without the prior consent of the Board of Directors of the Company unless compelled to do so by law.

8. Competition. For so long as you are employed by the Company or any Affiliate (as defined below) and for a period of one year after you cease to be employed by the Company or any Affiliate, you shall not, directly or indirectly, engage in any work or other activity–whether as owner, stockholder, partner, officer, consultant, or otherwise–involving a trademark, product, or process that, in the opinion of the Company's Chief Executive Officer, is similar to a trademark, product or process on which you worked for the Company (or any Affiliate) or obtained knowledge about while working for the Company at any time during the period of employment, if such work or other activity is then, or reasonably expected to become, competitive with that of the Company (or any Affiliate). The restriction in the preceding sentence shall not apply if you have disclosed to the Company in writing all the known facts relating to such work or activity and have received a release in writing from the Board of Directors of the Company allowing you to engage in such work or activity. The Company's Chief Executive Officer shall have sole discretion to determine whether your work or activity for another employer involves trademarks, products, or processes that are similar to trademarks, products, or processes that you worked on for the Company. Ownership by you of five percent (5%) or less of the outstanding shares of stock of any company either (i) listed on a national securities exchange, or (ii) having at least one hundred (100) stockholders shall not make you a 'stockholder' within the meaning of that term as used in this paragraph. For one year after you cease to work for the Company, you will not engage in any work or activity that will cause you to inevitably disclose to anyone not employed by the Company (or an Affiliate) any trade secret or confidential information that belongs to the Company or one of its Affiliates. Nothing in this paragraph shall limit the rights or remedies of the Company arising, directly or indirectly, from such competitive employment, including, without limitation, claims based upon breach of fiduciary duty, misappropriation, or theft of confidential information. The term 'Affiliate' shall mean the Company and any entity controlling, controlled by, or under common control with the Company.

9. Conflicting Contracts. You represent and warrant that you are not now under any obligation resulting from any contract or arrangement, to any person, firm, or corporation, which is inconsistent or in conflict with this Agreement. Likewise you represent and warrant that you are not now under any obligation resulting from any contract or arrangement to any person, firm, or corporation which would prevent, limit, or impair in any way the performance by you of your obligations to the Company.

10. Solicitation. After you cease to be employed by the Company (or a Company affiliate):

(a) You agree not to solicit, directly or indirectly, business related to the development or sales of pharmaceutical products from any entity, organization, or person which is contracted with the Company, which has been doing business with the Company or from which the Company was soliciting at the time of your termination, or a firm which you knew or had reason to know that the Company was going to

solicit business at the time you ceased to be employed by the Company. The restriction set forth in the preceding sentence shall not apply if you have disclosed to the Company in writing all the known facts relating to such solicitation and have received a release in writing from the Board of Directors of the Company to engage in such solicitation.

(b) You agree not to solicit, recruit, hire, or assist in the hiring of any employee of the Company to work for you or another person, firm, corporation, or business.

11. Return of Documents. Upon termination of your employment for any reason, you shall immediately return to the Company all documents and things belonging to the Company. This includes, but is not limited to, trade secrets, confidential information, knowledge, data or know-how, and software containing such information, whether or not the documents are marked 'Confidential.'

12. Remedies. You acknowledge that in the event of breach of this Agreement by you, actual damages to the Company will be impossible to calculate, the Company's remedies at law will be inadequate, and the Company will suffer irreparable harm. Therefore, you agree that any of the covenants contained in this Agreement may be specifically enforced through injunctive relief, but such right to injunctive relief shall not preclude the Company from other remedies which may be available to it. You further agree that should you fail to keep any of the promises made by you in this Agreement, or any way violate this Agreement, the Company shall be entitled to recover all monies the Company is required to spend, including attorneys' fees, to enforce the provisions of this Agreement.

13. Best Efforts and Conflicts of Interest: You are hired with the understanding that Cumberland is your sole employer and you will provide a full-time work effort. You agree to devote your entire professional and business-related time and best efforts to the services required of you by the express and implicit terms of this Agreement, to the reasonable satisfaction of Cumberland in its sole and complete discretion. Engaging in activities outside of work that create a conflict of interest, or detract from your ability to perform your assigned responsibilities or meet your defined goals and objectives with Cumberland, is a problem and may lead to disciplinary action up to and including termination of employment. If you believe that you are potentially involved in a situation that could create a conflict of interest and affect your ability to adequately perform your job with Cumberland, you should inform your direct supervisor and Cumberland's Human Resources Department immediately.

14. Standards of Business Conduct and Ethics.Cumberland's commitment to a culture of integrity, ethics and compliance with the law is comprised in this policy, which will be provided to you as part of the conditions of your employment. You will have the opportunity to read, discuss and understand this policy prior to accepting and signing its Letter of Agreement.

15. Debarment. You represent and warrant that you have not been debarred and will notify the Company immediately if you are debarred, pursuant to subsection 306(a) or 306(b) of the Federal Food, Drug, and Cosmetic Act.

16. Notice. Any notice required or permitted to be given under this Agreement shall be sufficient if in writing and if sent by registered or certified mail to your residence or to the Company's principal office in the case of the Company.

17 Waiver. The waiver by either party of any provision of this Agreement shall not operate or be construed as a waiver of any subsequent breach.

18. Entire Agreement. This Agreement contains the entire agreement of the parties and may not be changed orally, but only by an agreement in writing signed by the party against whom enforcement of any waiver, change, modification, extension, or discharge is sought.

19. Governance. This Agreement shall be governed by the laws of the State of Tennessee. Any dispute arising out of this Agreement shall be resolved, at the Company's sole option, by courts sitting in Nashville, Tennessee, and you waive any objection to such venue.

20. Enforceability. In the event that any provision of this Agreement shall be held by a court to be unenforceable, such provision will be enforced to the maximum extent permissible, and the remaining portions of this Agreement shall remain in full force and effect.

21. Survival. Notwithstanding any termination of your employment, this Agreement shall survive and remain in effect in accordance with its terms.

This letter agreement may be signed in one or more counterparts, each of which shall be an original and all of which will constitute one and the same instrument.

Cumberland Pharmaceuticals Inc.

We hereby consent to the incorporation by reference in the Registration Statements on Form S-3 (No. 333-221402) and Form S-8 (No. 333-164376) of Cumberland Pharmaceuticals Inc. of our report dated March 20, 2020, relating to the consolidated financial statements and financial statement schedule which appears in this Form 10-K.

I, A.J. Kazimi, certify that:

a.Designed such disclosure controls and procedures, or caused such disclosure controls and procedures to be designed under our supervision, to ensure that material information relating to the registrant, including its consolidated subsidiaries, is made known to us by others within those entities, particularly during the period in which this report is being prepared;

b.Designed such internal control over financial reporting, or caused such internal control over financial reporting to be designed under our supervision, to provide reasonable assurance regarding the reliability of financial reporting and the preparation of financial statements for external purposes in accordance with generally accepted accounting principles;

c.Evaluated the effectiveness of the registrant's disclosure controls and procedures and presented in this report our conclusions about the effectiveness of the disclosure controls and procedures, as of the end of the period covered by this report based on such evaluation; e

d.Disclosed in this report any change in the registrant's internal control over financial reporting that occurred during the registrant's most recent fiscal quarter (the registrant's fourth fiscal quarter in the case of an annual report) that has materially affected, or is reasonably likely to materially affect, the registrant's internal control over financial reporting; e

a.All significant deficiencies and material weaknesses in the design or operation of internal control over financial reporting which are reasonably likely to adversely affect the registrant's ability to record, process, summarize and report financial information; e

b.Any fraud, whether or not material, that involves management or other employees who have a significant role in the registrant's internal control over financial reporting.

I, Michael P. Bonner, certify that:

a.Designed such disclosure controls and procedures, or caused such disclosure controls and procedures to be designed under our supervision, to ensure that material information relating to the registrant, including its consolidated subsidiaries, is made known to us by others within those entities, particularly during the period in which this report is being prepared;

b.Designed such internal control over financial reporting, or caused such internal control over financial reporting to be designed under our supervision, to provide reasonable assurance regarding the reliability of financial reporting and the preparation of financial statements for external purposes in accordance with generally accepted accounting principles;

c.Evaluated the effectiveness of the registrant's disclosure controls and procedures and presented in this report our conclusions about the effectiveness of the disclosure controls and procedures, as of the end of the period covered by this report based on such evaluation; e

d.Disclosed in this report any change in the registrant's internal control over financial reporting that occurred during the registrant's most recent fiscal quarter (the registrant's fourth fiscal quarter in the case of an annual report) that has materially affected, or is reasonably likely to materially affect, the registrant's internal control over financial reporting; e

a.All significant deficiencies and material weaknesses in the design or operation of internal control over financial reporting which are reasonably likely to adversely affect the registrant's ability to record, process, summarize and report financial information; e

b.Any fraud, whether or not material, that involves management or other employees who have a significant role in the registrant's internal control over financial reporting.

PURSUANT TO 18 U.S.C. SECTION 1350,

In connection with the Annual Report of Cumberland Pharmaceuticals Inc. (the 'Company') on Form 10-K for the fiscal year ended December 31, 2019, as filed with the Securities and Exchange Commission on the date hereof (the 'Report'), I, A.J. Kazimi, Chief Executive Officer, and Michael P. Bonner, Senior Director and Chief Financial Officer, of the Company, certify, pursuant to Section 906 of the Sarbanes-Oxley Act of 2002 (18 U.S.C. section 1350), that, based on my knowledge:

1. The Report fully complies with the requirements of Section 13(a) or 15(d) of the Securities Exchange Act of 1934; e

2. The information contained in the Report fairly presents, in all material respects, the financial condition and results of operations of the Company.

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Nota del redattore: questa pagina viene aggiornata settimanalmente con nuove informazioni relative ai test COVID-19 e ai potenziali trattamenti in fase di sviluppo. Fai clic sulla freccia accanto alla data per espandere il testo.

1 luglio 2020

Gilead ha fissato il suo prezzo per il remdesivir antivirale sperimentale a $ 390 per fiala. Un corso di trattamento di cinque giorni di sei fiale della terapia, che si basa sugli attuali schemi di trattamento, equivarrà a $ 2.340 per paziente, ha dichiarato il CEO di Gilead Daniel O’Day in una lettera aperta. Negli Stati Uniti, tuttavia, il prezzo del trattamento per le compagnie assicurative private sarà di $ 520 per flaconcino, a causa delle caratteristiche uniche del sistema statunitense e degli sconti previsti dai programmi sanitari del governo. Secondo O’Day, questo prezzo eliminerà la necessità di negoziati sui prezzi paese per paese. Gilead ha stipulato accordi con produttori di farmaci generici per fornire cure a un costo inferiore nei paesi in via di sviluppo. Remdesivir ha mostrato risultati promettenti negli studi clinici contro COVID-19.

FibroGen ha iniziato uno studio di fase 2 su pamrevlumab per il trattamento di pazienti COVID-19 ospedalizzati. Pamrevlumab è un anticorpo monoclonale sperimentale che viene anche testato per il trattamento della fibrosi polmonare idiopatica, del carcinoma pancreatico non resecabile localmente avanzato e della distrofia muscolare di Duchenne. Lo studio randomizzato (NCT04432298), che sta attivamente reclutando partecipanti negli Stati Uniti, valuterà la sicurezza e l'efficacia di pamrevlumab in un massimo di 130 pazienti con COVID-19 acuto, rispetto a un placebo. Ulteriori informazioni sull'iscrizione sono disponibili qui.

La Food and Drug Administration degli Stati Uniti ha approvato il lancio dello studio di Fase 3 di Fulcrum Therapeutics sul suo farmaco antinfiammatorio sperimentale losmapimod per il trattamento di pazienti COVID-19 ospedalizzati. Lo studio internazionale randomizzato, chiamato LOSVID, arruolerà circa 400 pazienti COVID-19 a rischio di progredire verso malattie critiche basate sull'età avanzata e un'infiammazione sistemica elevata. I partecipanti saranno randomizzati a 15 mg due volte al giorno di losmapimod o un placebo, oltre alle cure standard, per 14 giorni. La misura principale dello studio è la percentuale di pazienti che progrediscono fino alla morte o all'insufficienza respiratoria entro il giorno 28. I dati di punta dello studio sono attesi all'inizio del 2021.

Catalent e Moderna hanno firmato un accordo per riempire e impacchettare 100 milioni di dosi del candidato al vaccino mRNA di Moderna – noto come mRNA-1273 – con il potenziale di produrre centinaia di milioni in più. Le aziende sperano di poter iniziare a distribuire dosi negli Stati Uniti entro la fine dell'anno. Catalent ha siglato accordi simili con Johnson & Johnson e AstraZeneca.

Il candidato al vaccino COVID-19 di Vaxart è stato selezionato per partecipare a uno studio sui primati finanziato dall'operazione Warp Speed ​​del governo degli Stati Uniti, ha annunciato la compagnia. Vaxart sta sviluppando questo vaccino e altri nella sua pipeline, come compresse orali, piuttosto che come soluzione liquida iniettabile. “Vaxart ritiene che un vaccino con compresse stabili a temperatura ambiente sia più facile da distribuire, conservare e somministrare rispetto ai vaccini iniettabili e possa fornire una risposta significativamente più rapida a una pandemia rispetto ai vaccini iniettabili”, ha dichiarato la società in un comunicato stampa.

Il comando di ricerca e sviluppo medico dell'esercito americano ha assegnato $ 4,7 milioni ad Altimmune per finanziare uno studio di fase 1/2 (NCT04442230) di T-COVID, un trattamento ambulatoriale sperimentale COVID-19. T-COVID è un modulatore immunitario intranasale (somministrato attraverso il naso), progettato per impedire ai pazienti di progredire in una grave malattia. Altimmune prevede di iniziare a reclutare partecipanti per la sperimentazione nelle prossime settimane e di produrre i dati della sperimentazione entro la fine dell'anno.

L'Organizzazione Mondiale della Sanità ha svelato piani per garantire 2 miliardi di dosi di un futuro vaccino COVID-19 entro la fine del 2021. Il piano prevede che i paesi mettano in comune le proprie risorse per investire in un'ampia selezione di vaccini sperimentali, diffondendo così il rischio di scommettere su qualsiasi candidato in particolare. L'OMS stima che saranno necessari 31,3 miliardi di dollari di finanziamenti nei prossimi 12 mesi per eseguire il suo piano. Ad oggi, 3,4 miliardi di dollari sono stati garantiti dai paesi partecipanti.

L'Imperial College di Londra ha dosato il primo partecipante a una sperimentazione di Fase 1 del suo candidato al vaccino COVID-19. Inizialmente i ricercatori hanno in programma di reclutare 15 volontari sani, nei quali testeranno la sicurezza di aumentare le dosi del potenziale vaccino. Successivamente, l'obiettivo è di aumentare il numero di prove a 300 partecipanti, con prove più grandi in programma per la fine dell'anno. Il processo sta reclutando attivamente; Ulteriori informazioni possono essere trovate qui.

Inovio ha recentemente annunciato risultati positivi per il suo candidato al vaccino COVID-19, INO-4800. Secondo la società, il 94% dei 36 volontari sani trattati con il potenziale vaccino in uno studio di fase 1 ha dimostrato una risposta immunologica, ma ha fornito pochi altri dettagli di supporto. INO-4800 è stato anche selezionato per studi preclinici sui primati nell'ambito del programma Operation Warp Speed. La società sta anticipando il lancio di una prova di efficacia di Fase 2/3 entro l'estate.

24 giugno 2020

Il Dipartimento della salute e dei servizi umani degli Stati Uniti ha recentemente pubblicato una scheda informativa che spiega il programma Operation Warp Speed ​​annunciato a metà maggio. Le aziende farmaceutiche selezionate per il programma, che è un partenariato pubblico-privato volto a stimolare lo sviluppo di vaccini, terapeutici e diagnostici COVID-19, avranno accesso prioritario alla capacità produttiva e alle forniture necessarie. L'obiettivo dell'operazione Warp Speed ​​è di fornire 300 milioni di dosi di un vaccino sicuro ed efficace all'inizio del prossimo anno. Sono già stati identificati quattordici candidati al vaccino, di cui sette dei più promettenti saranno scelti per avanzare agli studi nella fase iniziale. Quei candidati che hanno successo nei primi studi passeranno poi ai test in prove su larga scala.

Allo stesso tempo, l'Unione Europea ha lanciato la propria strategia per coordinare lo sviluppo del vaccino per COVID-19, con l'obiettivo di avere vaccini sicuri ed efficaci disponibili entro 12-18 mesi. La Commissione europea dedicherà una parte significativa di un fondo di emergenza di circa 3 miliardi di dollari per far avanzare gli acquisti di potenziali vaccini COVID-19 da parte di aziende, con ulteriore supporto reso disponibile attraverso prestiti della Banca europea per gli investimenti. La commissione ha inoltre proposto uno sforzo globale in cui i paesi ad alto reddito dovrebbero sostenere i paesi a basso e medio reddito nella prenotazione dei vaccini, in modo che i paesi di tutti i livelli di reddito abbiano accesso a misure di salvataggio, quando saranno disponibili.

L'autorità di regolamentazione dei medicinali e dei prodotti sanitari del Regno Unito ha sospeso il reclutamento per studi clinici sull'idrossiclorochina come potenziale trattamento per COVID-19. La decisione segue i dati di due studi, incluso lo studio RECOVERY su larga scala (NCT04381936), che ha scoperto che il farmaco non fornisce alcun beneficio significativo ai pazienti ospedalizzati COVID-19. L'agenzia consiglia a coloro che assumono idrossiclorochina e clorochina per altre condizioni di continuare a farlo, come consigliato dal proprio medico.

Allo stesso modo, l'Organizzazione mondiale della sanità ha sospeso il braccio idrossiclorochina del suo studio globale sulla solidarietà, che sta cercando trattamenti efficaci per i pazienti con COVID-19. La decisione dell'OMS si basava sui risultati trovati nel processo di solidarietà, nonché su quelli del processo di RECUPERO e altre prove esaminate. Secondo l'organizzazione, la sua decisione non si applica all'uso dell'idrossiclorochina come trattamento preventivo tra coloro che sono stati esposti al virus.

Dopo risultati positivi in ​​un altro braccio dello studio RECOVERY, il Regno Unito ha autorizzato il Servizio sanitario nazionale a trattare COVID-19 con desametasone. I risultati dei test annunciati la scorsa settimana hanno mostrato che il medicinale ha ridotto il rischio di morte tra i pazienti che necessitano sia di ventilazione sia di terapie con solo ossigeno. Il governo ha già preso provvedimenti per garantire le forniture di medicinali e attualmente ha abbastanza per curare più di 200.000 persone.

Gilead Sciences inizierà presto l'arruolamento per uno studio in aperto di Fase 2/3 (NCT04431453) per testare il farmaco antivirale remdesivir tra i bambini ospedalizzati con COVID-19. Lo studio valuterà la sicurezza, la tollerabilità, la farmacocinetica di Remdesivir (movimento nel corpo) e l'efficacia tra circa 50 pazienti, dai neonati agli adolescenti, con COVID-19 da lieve a grave. Questo processo si svolgerà in oltre 30 siti negli Stati Uniti e in Europa. Gilead fornisce remdesivir ai bambini con grave COVID-19 sotto uso compassionevole da febbraio.

Clover Biopharmaceuticals ha iniziato uno studio randomizzato di Fase 1 (NCT04405908) del suo candidato al vaccino COVID-19, SCB-2019, in Australia. Lo studio, che sta arruolando circa 150 pazienti, testerà SCB-2019 insieme a farmaci adiuvanti (assistenti) da GlaxoSmithKline e Dynavax. Il primo paziente è stato recentemente dosato e la società prevede risultati preliminari ad agosto.

Sanofi intende iniziare una sperimentazione di Fase 1/2 del suo candidato al vaccino COVID-19 a settembre. Se tutto va bene, la società prevede la piena approvazione all'inizio del 2021. Questa sequenza temporale accelera ciò che la società aveva precedentemente proposto, quando ha accettato di sviluppare il vaccino con GlaxoSmithKline. Sanofi sta inoltre pianificando di iniziare una sperimentazione di Fase 1 entro la fine dell'anno, testando un candidato al vaccino mRNA sviluppato in collaborazione con Translate Bio. In attesa di risultati positivi, punta all'approvazione nella seconda metà del 2021.

Glenmark Pharmaceuticals ha ricevuto l'approvazione per l'uso in emergenza in India del suo favipiravir antivirale influenzale per il trattamento di COVID-19 da lieve a moderato. Questo segna il primo farmaco autorizzato per il trattamento di COVID-19 nel paese. La società intende commercializzare la terapia con il marchio FabiFlu. Glenmark sta conducendo contemporaneamente uno studio di Fase 3 su favipiravir come monoterapia COVID-19 in nove siti in tutta l'India.

17 giugno 2020

Il desametasone ha dimostrato di ridurre il rischio di morte tra i pazienti COVID-19 che necessitano di ossigeno supplementare, secondo i risultati dello studio di Fase 2/3 RECOVERY (NCT04381936), uno studio britannico che sta testando una varietà di potenziali terapie per curare il virus. Il desametasone è uno steroide generico spesso prescritto per il trattamento di condizioni infiammatorie. Durante la sperimentazione, il trattamento ha ridotto il rischio di morte di un terzo tra i pazienti che necessitano di ventilazione e di un quinto solo nei pazienti sottoposti a terapia con ossigeno. Non ha mostrato alcun beneficio nei pazienti che non necessitano di supporto respiratorio. I ricercatori stanno ora lavorando per convalidare e pubblicare i risultati della sperimentazione.

La Food and Drug Administration statunitense ha ora revocato l'autorizzazione all'uso di emergenza per clorochina fosfato e idrossiclorochina solfato per il trattamento di COVID-19. Sulla base delle prove disponibili, l'agenzia ha stabilito che è improbabile che i regimi di dosaggio suggeriti per i due trattamenti producano un effetto antivirale, che le osservazioni sulla riduzione della diffusione virale attribuita al loro uso non siano state replicate in modo coerente e che i recenti dati degli studi clinici non mostrino prove di il loro beneficio nel trattamento di COVID-19. Secondo la lettera della FDA, i benefici noti e potenziali di questi trattamenti non superano i rischi noti e potenziali.

Moderna, in collaborazione con il National Institutes of Health degli Stati Uniti, ha in programma di lanciare uno studio di fase 3 controllato con placebo da 30.000 persone sul suo vaccino candidato COVID-19 a luglio. L'obiettivo principale dello studio è determinare se il vaccino, noto come mRNA-1273, può prevenire la COVID-19 sintomatica. Le misure secondarie metteranno alla prova la capacità del vaccino di prevenire l'infezione o il ricovero in ospedale. Il primo gruppo di volontari sani è stato completamente arruolato nell'attuale studio di Fase 2 (NCT04405076) per testare il vaccino, che ha ottenuto la designazione accelerata dalla FDA a maggio.

I ricercatori delle università di Birmingham e Oxford nel Regno Unito stanno proiettando il namilumab di Izana Bioscience e Remsima (infliximab) di Celltrion Healthcare per il trattamento di COVID-19 nell'ambito dello studio CATALYST multi-braccio e multistadio. Namilumab è un anticorpo monoclonale umano già in fase di sperimentazione clinica in fase avanzata per il trattamento dell'artrite reumatoide, della spondilite anchilosante e della psoriasi a placche. Infliximab è usato per trattare le condizioni infiammatorie, tra cui otto malattie autoimmuni. L'obiettivo dello studio CATALYST è quello di identificare le terapie esistenti che hanno il potenziale per trattare COVID-19 e possono essere incanalate in grandi studi di fase 3 in pazienti ospedalizzati.

L'Agenzia europea per i medicinali ha rilasciato una dichiarazione in cui consiglia ai pazienti di continuare a prendere la pressione sanguigna e i farmaci per il cuore come indicato dai loro medici durante la pandemia. Secondo l'agenzia, l'uso di inibitori dell'enzima di conversione dell'angiotensina e bloccanti del recettore dell'angiotensina non ha mostrato alcun effetto negativo sui pazienti con COVID-19 in numerosi studi. L'EMA afferma che continuerà a monitorare i dati e fornirà consulenza continua sulla sicurezza dei medicinali in collaborazione con altri regolatori e organizzazioni internazionali.

Regeneron ha iniziato i primi studi di Fase 1/2 (NCT04425629 e NCT04426695) per testare REGN-COV2, un cocktail di anticorpi, per il trattamento di COVID-19 in pazienti ospedalizzati e non ospedalizzati. Il programma clinico includerà anche studi che valuteranno la capacità di REGN-COV2 di prevenire COVID-19 in altri due gruppi: soggetti non infetti ad alto rischio di esposizione e individui non infetti con stretta esposizione a un paziente COVID-19. I dati di fase 1/2 verranno utilizzati per guidare il protocollo per gli studi di fase 3 successivi.

AstraZeneca ha concesso in licenza sei potenziali anticorpi COVID-19 della Vanderbilt University e prevede di iniziare a testarne una combinazione entro due mesi. La compagnia ha siglato accordi con l'Autorità di ricerca e sviluppo avanzata biomedica e l'Agenzia per i progetti di ricerca avanzata di difesa, entrambe le agenzie governative statunitensi, per contribuire a portare avanti questo sforzo.

Eli Lilly ha iniziato ad arruolare pazienti in uno studio di Fase 3 (NCT04421027) per testare il suo trattamento contro l'artrite reumatoide Olumiant (baricitinib) in pazienti COVID-19 ospedalizzati. Questo studio, che integrerà altri studi in corso su baricitinib in pazienti COVID-19, valuterà la percentuale di pazienti trattati con 4 mg di Olumiant che muoiono o necessitano di ventilazione entro il giorno 28, rispetto a quelli trattati con placebo. Lilly prevede di arruolare circa 400 pazienti negli Stati Uniti, Germania, Spagna e Messico.

I risultati preliminari di uno studio randomizzato di Fase 1/2 (NCT04352608) hanno mostrato che il candidato al vaccino COVID-19 di Sinovac, CoronaVac, ha indotto una risposta immunitaria tra i pazienti. Secondo la società con sede a Pechino, oltre il 90% dei partecipanti ha generato anticorpi neutralizzanti dopo aver ricevuto il vaccino e che non si sono verificati eventi avversi gravi. La società prevede di far avanzare il vaccino a uno studio di fase 3 “nel prossimo futuro”.

10 giugno 2020

Gilead Sciences ha richiesto l'approvazione nell'Unione europea di remdesivir per il trattamento di COVID-19, secondo l'Agenzia europea per i medicinali, che ha ricevuto una domanda di autorizzazione all'immissione in commercio condizionata per il trattamento. Poiché alcuni dei dati erano già stati sottoposti a revisione periodica, l'agenzia prevede di completare la revisione dei dati in tempi brevi. Se le informazioni presentate sono ritenute sufficienti, l'agenzia collaborerà con la Commissione europea per accelerare potenzialmente l'approvazione della terapia.

L'idrossiclorochina non fornisce alcun beneficio ai pazienti con COVID-19, secondo i risultati preliminari dello studio clinico RECUPERO fase 2/3 (NCT04381936). Lo studio randomizzato, che ha arruolato oltre 11.000 pazienti nel Regno Unito e sta testando una varietà di terapie per curare il virus, ha scoperto che l'antimalarico non ha mostrato alcun effetto benefico sulla durata delle degenze ospedaliere né su altri esiti della malattia. Sulla base di questi risultati, i ricercatori hanno deciso di interrompere l'arruolamento dei pazienti nel braccio idrossiclorochina della sperimentazione.

Mentre continua la controversia sull'idrossiclorochina, The Lancet il diario ha recentemente ritirato l'articolo “Idrossiclorochina o clorochina con o senza un macrolide per il trattamento di COVID-19: un'analisi del registro multinazionale“. I risultati dello studio hanno mostrato che non vi sono stati benefici per il trattamento con idrossiclorochina o clorochina sugli esiti ospedalieri per COVID-19, ma tre autori del documento hanno deciso di ritirarsi in base al fatto che non erano riusciti a completare un audit indipendente dei dati su cui si basavano i loro analisi. Per questo motivo, hanno scritto in una dichiarazione per The Lancet, “non possono più garantire la veridicità delle origini dati primarie”.

Il Ministero della Salute brasiliano ha approvato studi clinici su AstraZeneca e il candidato al vaccino COVID-19 dell'Università di Oxford, rendendolo il primo paese al di fuori del Regno Unito a farlo. Il candidato al vaccino, noto come ChAdOx1 nCoV-19 e AZD1222, è uno dei primi a passare ai test di fase 2. Reuters ha riferito che questo vaccino entrerà simultaneamente in entrambi gli studi di Fase 2 e Fase 3 per accelerarne lo sviluppo. Il primo ciclo di prove, condotto dall'Università Federale di San Paolo e finanziato dalla Fondazione Lemann del Brasile, testerà il vaccino in 2000 volontari che non hanno precedentemente contratto il COVID-19.

Inovio inizierà a testare il suo candidato al vaccino COVID-19, INO-4800, in uno studio di Fase 1/2 in Corea del Sud alla fine di questo mese in collaborazione con l'Istituto internazionale per i vaccini e l'ospedale universitario nazionale di Seoul. Lo studio valuterà la sicurezza, la tollerabilità e la capacità del vaccino di produrre una risposta immunitaria in 40 adulti, di età compresa tra 19 e 50 anni. Inovio prevede di espandere questo processo per includere altre 120 persone di età compresa tra 19 e 64 anni.

Eli Lilly ha collaborato con la biotecnologia di Shanghai Junshi Biosciences per iniziare a testare un secondo potenziale vaccino COVID-19. Simile al primo candidato di Eli Lilly, noto come LY-CoV555, JS016 è anche un anticorpo ingegnerizzato che ha mostrato risultati promettenti negli studi preclinici nella neutralizzazione del virus SARS-CoV-2, che causa COVID-19. Il primo volontario in buona salute in uno studio randomizzato di Fase 1 è stato recentemente somministrato all'Ospedale Huashan affiliato all'Università di Fudan in Cina.

AbbVie ha collaborato con Harbour BioMed, l'Università di Utrecht e il Centro medico Erasmus per sviluppare 47D11, una terapia anticorpale monoclonale per COVID-19. AbbVie supporterà i suoi partner attraverso attività precliniche mentre si prepara allo sviluppo preclinico e clinico della fase successiva. Secondo i termini del loro accordo, AbbVie avrà anche la possibilità di concedere in licenza esclusivamente l'anticorpo per lo sviluppo terapeutico e la commercializzazione in tutto il mondo.

La biotecnologia australiana CSL, insieme all'Università del Queensland (UQ) e alla Coalition for Epidemic Preparedness Innovations (CEPI), hanno unito le forze per accelerare lo sviluppo di un candidato al vaccino COVID-19 sviluppato per la prima volta da UQ. CSL e CEPI finanzieranno la produzione su scala industriale di potenzialmente 100 milioni di dosi di vaccino entro la fine del 2021, qualora il prodotto dovesse ottenere l'approvazione.

La ricerca preliminare mostra che il trattamento del cancro del sangue di AstraZeneca Calquence (acalabrutinib) offre un beneficio ai pazienti ospedalizzati con COVID-19. Dei 19 pazienti con COVID-19 gravi trattati con Calquence, 11 che avevano avuto bisogno di ossigeno supplementare non ne avevano più bisogno e quattro su otto pazienti sottoposti a ventilazione meccanica sono stati portati via con successo. La società ha affermato che i risultati positivi supportano il lancio di un processo globale di Fase 2, annunciato ad aprile.

FibroGen ha arruolato il primo paziente in uno studio di Fase 2/3 in Italia per valutare il trattamento con fibrosi polmonare pamrevlumab per COVID-19 grave. Lo studio valuterà l'effetto di pamrevlumab sull'ossigenazione del sangue in 68 pazienti ospedalizzati che riceveranno pamrevlumab o cure standard. La società sta inoltre pianificando due studi di fase 2 negli Stati Uniti per valutare il pamrevlumab rispetto alle cure standard in pazienti con COVID-19 grave.

3 giugno 2020

Gilead ha annunciato i migliori risultati del suo semplice studio clinico di Fase 3 (NCT04292899) per testare la sicurezza e l'attività antivirale di remdesivir. Secondo i risultati, i pazienti che hanno ricevuto il trattamento con remdesivir per cinque giorni avevano il 65% in più di probabilità di migliorare clinicamente al giorno 11 rispetto a quelli che avevano ricevuto cure standard.

Un rapporto preliminare di 1.059 pazienti che hanno partecipato a un altro studio di Fase 3 chiamato ACTT (NCT04280705), valutando gli effetti di remdesivir per il trattamento di COVID-19, è stato pubblicato in Il New England Journal of Medicine. I primi risultati mostrano che remdesivir è stato superiore a un placebo nel ridurre i tempi di recupero negli adulti ricoverati in ospedale con COVID-19 e infezione del tratto respiratorio inferiore.

Con i primi dati che dimostrano che redemsivir può accelerare i tempi di recupero, alcuni pazienti nel Regno Unito ricoverati in ospedale con COVID-19 che soddisfano criteri specifici saranno presto in grado di accedere alla terapia sperimentale. I pazienti saranno selezionati in base a consigli clinici esperti per il massimo beneficio potenziale. Il piano è supportato dal governo del Regno Unito, da Gilead, dal Servizio sanitario nazionale e dall'Agenzia di regolamentazione per i medicinali e i prodotti sanitari. Remdesivir non è stato ancora approvato per alcuna indicazione.

BerGenBio ha dosato il primo paziente nel suo studio di fase 2, testando l'inibitore orale della chinasi bemcentinib, insieme alle cure standard, in pazienti COVID-19 ospedalizzati. Il candidato al trattamento è il primo ad essere selezionato come parte della piattaforma Accordating COVID-19 Research & Development (ACCORD) del Regno Unito, un'iniziativa progettata per testare rapidamente potenziali terapie COVID-19 nelle prime prove prima di inviarle in studi su larga scala . Il processo sta reclutando circa 120 partecipanti in otto siti nel Regno Unito.

I primi pazienti sono stati dosati in uno studio di Fase 1 (NCT04411628) condotto da Lilly e AbCellera per testare un trattamento anticorpale contro COVID-19 chiamato LY-CoV55. Questo segna il primo studio al mondo sull'uomo che valuta un anticorpo per il trattamento del virus. Lo studio randomizzato a dose singola ascendente sta valutando la sicurezza, la tollerabilità, la farmacocinetica (movimento nel corpo) e la farmacodinamica (effetto sul corpo) di LY-CoV555 somministrata per via endovenosa in pazienti ricoverati con COVID-19. Il processo, che arruolerà circa 40 partecipanti, è attualmente aperto al reclutamento in più siti negli Stati Uniti e dovrebbe essere completato il 23 agosto.

La società ha annunciato che un anticorpo antivirale sperimentale sviluppato da Celltrion per COVID-19 ha mostrato risultati positivi in ​​uno studio preclinico. Lo studio ha testato l'efficacia di una dose alta e bassa del candidato al trattamento in un modello animale. I risultati hanno mostrato che la terapia ha portato a una riduzione di cento volte della carica virale e ha ridotto le lesioni polmonari a un livello normale.

Advent ha prodotto 13.000 dosi di AZD1222, il vaccino sperimentale COVID-19 di AstraZeneca, da utilizzare nei test clinici. Secondo la società manifatturiera con sede in Italia, ha consegnato 4.000 dosi all'Università di Oxford per lo studio di Fase 2/3 COV002 (NCT04400838), che ha lo scopo di testare il potenziale vaccino in oltre 10.000 volontari sani. Non è ancora aperto al reclutamento.

Massachusetts Eye and Ear e Massachusetts General Hospital hanno stretto una partnership con AveXis per sviluppare un nuovo potenziale vaccino genetico, chiamato AAVCOVID, contro COVID-19. L'ospedale condurrà test di sicurezza ed efficacia in studi preclinici, mentre AveXis inizierà a produrre il vaccino. Utilizzerà un approccio di terapia genica, in cui un virus adeno-associato innocuo fornirà un codice genetico alle cellule umane per produrre porzioni di SARS-CoV-2, il virus che causa COVID-19, per suscitare una risposta immunitaria.

PureTech inizierà gli studi clinici sull'uomo per testare il suo trattamento sperimentale LYT-100 (deupirfenidone) nelle persone con complicanze respiratorie a seguito del recupero da infezioni COVID-19. LYT-100, un analogo del trattamento della fibrosi polmonare Esbriet (pirfenidone) è attualmente in fase di sperimentazione in uno studio di fase 1 (NCT04243837) su volontari sani e pazienti con linfedema correlato al carcinoma mammario per sicurezza, tollerabilità e farmacocinetica.

27 maggio 2020

I risultati del primo potenziale vaccino COVID-19 da testare in uno studio clinico di fase 1 (NCT04313127) sono stati recentemente pubblicati sulla rivista The Lancet. Hanno dimostrato che il vaccino COVID-19 (Ad5-nCoV) vettoriale tipo adenovirus 5 era tollerabile e in grado di innescare una risposta immunitaria già 14 giorni dopo la vaccinazione. I ricercatori hanno concluso che il potenziale vaccino merita ulteriori indagini, ma hanno avvertito che sono ancora molto lontani dall'avere un vaccino COVID-19 disponibile per tutti.

Novavax sta arruolando i primi partecipanti a una sperimentazione di Fase 1/2 per testare il suo candidato al vaccino, NVX ‑ CoV2373. Lo studio è stato condotto in due parti, la prima delle quali si sta svolgendo in Australia e sta testando la sicurezza e la risposta immunitaria in volontari sani, dai 18 ai 59 anni. La parte di Fase 2 sarà condotta in più paesi e includerà una più ampia fascia di età per testare la sicurezza, l'immunità e la capacità del vaccino di ridurre la malattia COVID-19.

Glenmark Pharmaceuticals sta lanciando uno studio di Fase 3 in India per verificare se il trattamento precoce con favipiravir e umifenovir migliora l'efficacia della combinazione antivirale in pazienti COVID-19 ospedalizzati. Si prevede che lo studio arruolerà circa 158 partecipanti con COVID-19 moderato, che saranno randomizzati a ricevere favipiravir con o senza umifenovir, oltre alle cure standard.

Covis Pharma ha annunciato l'avvio di uno studio di fase 3 (NCT04377711) per valutare la sicurezza e l'efficacia del farmaco per l'asma Alvesco (ciclesonide) nelle persone con sintomi di COVID-19, di età pari o superiore a 12 anni che non sono ricoverati in ospedale. I ricercatori pensano che il trattamento possa sopprimere la replicazione virale e alleviare i sintomi della malattia. Il trial multicentrico e randomizzato dovrebbe reclutare 400 partecipanti negli Stati Uniti e si stima che sarà completato entro la fine dell'anno.

Un nuovo studio (NCT04303507) condotto dall'Università di Oxford e dall'unità di ricerca sulla medicina tropicale di Mahidol Oxford in Thailandia sta reclutando partecipanti per testare l'effetto della clorochina e dell'idrossiclorochina su COVID-19. Lo studio randomizzato arruolerà circa 40.000 operatori sanitari in Europa, Africa, Asia e Sud America che hanno avuto stretti contatti con pazienti con COVID-19 provato o sospetto. Al momento non ci sono prove conclusive che la clorochina o l'idrossiclorochina possano prevenire o trattare COVID-19.

Octapharma sta lanciando uno studio di fase 3 per verificare se Octagam 10%, la sua terapia con immunoglobuline per via endovenosa, può rallentare o prevenire il deterioramento respiratorio nei pazienti COVID-19. Lo studio multicentrico e randomizzato arruolerà 54 pazienti con COVID-19 grave in circa 10 siti negli Stati Uniti Octagam 10% è un trattamento approvato per la porpora trombocitopenica immune cronica negli adulti.

L'IMV ha selezionato un candidato al vaccino contro COVID-19 che prevede di avanzare negli studi sull'uomo. Il vaccino, chiamato DPX-COVID-19, si basa su epitopi peptidici che hanno mostrato solide risposte immunitarie e anticorpali negli studi preclinici. La società prevede di lanciare uno studio di fase 1 per testare il potenziale vaccino questa estate.

AstraZeneca ha messo a punto accordi per i primi 400 milioni di dosi del suo candidato vaccino in fase di sviluppo presso l'Università di Oxford. Ha già garantito la capacità produttiva per 1 miliardo di dosi e prevede di iniziare le prime consegne a settembre. Il vaccino, chiamato AZD1222, (precedentemente ChAdOx1 nCoV-19) è in fase di test in uno studio di Fase 1/2 (NCT04324606) per determinare la sicurezza, l'efficacia e la risposta immunitaria in oltre 1.000 volontari sani.

20 maggio 2020

Moderna ha annunciato risultati provvisori positivi da uno studio clinico di Fase 1 (NCT04283461) che ha testato il suo potenziale vaccino COVID-19 mRNA-1273. Lo studio, condotto dal National Institutes of Health, sta testando tre diverse dosi di mRNA-1273 in volontari sani di età compresa tra 18 e 55 anni per sicurezza, risposta immunitaria ed effetti avversi. I risultati finora dimostrano che il vaccino è generalmente sicuro e ben tollerato. Moderna sta pianificando uno studio di fase 2 per testare ulteriormente il potenziale vaccino e determinare la dose giusta da utilizzare negli studi cardine che dovrebbero iniziare a luglio. Il processo di Fase 1 sta ancora reclutando volontari sani in Georgia, Maryland e Washington.

NeuroRx sta sponsorizzando uno studio di fase 2b / 3 (NCT04360096) che testerà l'aviptadil in pazienti con COVID-19 in condizioni critiche. L'obiettivo dello studio è identificare i pazienti con COVID-19 con danno polmonare non acuto e trattarli con aviptadil nella speranza di prevenire la progressione da danno polmonare non acuto a acuto e sindrome da distress respiratorio acuto, o ARDS, entrambe le complicanze associate a COVID -19. Lo studio multicentrico, randomizzato, controllato con placebo assumerà circa 144 partecipanti con COVID-19 e prove di danno polmonare. Le iscrizioni non sono ancora aperte.

Stanford Medicine sta attualmente arruolando partecipanti in uno studio di Fase 2 (NCT04331899) per verificare se il peginterferone lambda-1a può aiutare i pazienti a recuperare più velocemente e limitare lo spargimento virale, il che riduce il rischio di trasmissione ad altri. Lo studio randomizzato in aperto sta reclutando circa 120 partecipanti in California, dai 18 ai 64 anni, con una diagnosi iniziale di COVID-19 e sintomi di infezione respiratoria senza difficoltà respiratoria. Il peginterferone lambda-1a è un antivirale che è già stato testato contro i virus che causano l'epatite.

L'Università di Oxford ha avviato uno studio nel Regno Unito che metterà alla prova la capacità di trattamenti esistenti come l'idrossiclorochina e l'azitromicina per prevenire, rallentare o addirittura arrestare la progressione di COVID-19 e ridurre la gravità dei suoi sintomi, evitando i ricoveri ospedalieri in persone di età superiore ai 50 anni.

La FDA ha completato la revisione della nuova applicazione sperimentale di ViralClear per Merimepodib per il trattamento di adulti con COVID-19 avanzato. Ciò significa che la società può ora iniziare la sperimentazione di Fase 2 proposta per testare il potenziale trattamento. Lo studio sarà randomizzato, in doppio cieco e controllato con placebo e dovrebbe essere condotto in più siti negli Stati Uniti. Testerà la sicurezza e l'efficacia di merimepodib negli adulti infetti da SARS-CoV-2 e ricoverato in ospedale richiedendo un supplemento ossigeno.

Risultati intermedi di uno studio multicentrico e randomizzato condotto in Russia per testare Avigan (favipiravir) hanno mostrato che il 60% dei 40 pazienti con COVID-19 che hanno ricevuto il trattamento è risultato negativo per il virus dopo cinque giorni, secondo il Russian Direct Investment Fund, che è finanziare lo studio. Si prevede che il processo includa 330 partecipanti con confermato COVID-19 in siti in tutta la Russia. Avigan è un antivirale sviluppato per la prima volta in Giappone per il trattamento dell'influenza.

Results from an observational study in France show that hydroxychloroquine does not significantly lower admissions to intensive care or death in patients hospitalized with pneumonia due to COVID-19. In addition, a randomized trial in China found that patients with mild to moderate COVID-19 treated with the anti-malarial drug did not clear the virus quicker than those receiving standard care. More adverse events were also recorded in patients treated with hydroxychloroquine. Findings from both studies, published in The BMJ journal, add to growing evidence that hydroxychloroquine may not be effective against COVID-19.

May 13, 2020

Moderna’s investigational mRNA vaccine for COVID-19, called mRNA-1273, was awarded the FDA’s fast-track designation, the first to receive this status, which is intended to speed up the review time for a potential medication. The company anticipates launching a Phase 3 trial testing the vaccine in early summer.

An observational study conducted by the University of Albany and the New York State Department of Health found no benefit to treating COVID-19 patients with hydroxychloroquine. This is at least the third such study to reach this conclusion, according to the FDA. After reviewing the medical records of 1,438 patients from 25 hospitals in the greater New York area, the researchers found that treatment with hydroxychloroquine, azithromycin, or both did not significantly lower the in-hospital death rate. The study was published in the Journal of the American Medical Association.

Novartis e Incyte are rolling out a second Phase 3 trial to test the safety and efficacy of Jakafi (ruxolitinib) compared with standard care in patients with COVID-19 who develop acute respiratory distress syndrome. Jakafi is a prescription medication for polycythemia vera, myelofibrosis, e acute graft-versus-host disease. The trial will be conducted in the U.S. The companies had previously announced a Phase 3 trial called RUXCOVID, which is examining Jakafi’s effectiveness in treating COVID-19-associated cytokine storm. That trial is currently underway.

A new Phase 2 trial is being planned to investigate the effectiveness of remdesivir with Olumiant (baricitinib) in treating COVID-19. It is expected to enroll up to 1,000 participants at 100 sites worldwide. Enrollment has already begun in the U.S. Remdesivir is an investigational broad-spectrum antiviral being developed by Gilead. It is not yet approved anywhere in the world for any indication. Olumiant is an anti-inflammatory by Lilly used to treat some patients with rheumatoid arthritis. The trial, being sponsored by the National Institute of Allergy and Infectious Diseases, follows on the heels of another study that found that remdesivir on its own shortened patients’ recovery time over a placebo.

A Phase 2 trial (NCT04276688) conducted in China tested a combination of three antivirals, Kaletra (lopinavir-ritonavir), an HIV antiviral, ribavirin, a hepatitis C treatment, and interferon beta-1, a treatment used in multiple sclerosis. The trial, completed on March 31, showed that the combo therapy suppressed the virus at day seven. This was five days earlier than in patients who were treated with Kaletra only. The combo was also found to be safe, leading to minor gastrointestinal side effects such as diarrhea and vomiting.

The FDA concesso emergency use authorization for a new laboratory test kit to detect SARS-CoV-2. The kit, called OPTI SARS-CoV-2 RT-PCR, can detect the genetic material of the virus in oral and nasal swabs as well as sputum.

May 6, 2020

The U.S. Food and Drug Administration has granted Gilead Sciences’ remdesivir emergency use authorization for the treatment of COVID-19, the company recently announced. The agency’s decision was based on available data from two global Phase 3 clinical trials.

Top-line results from one of these Phase 3 trials, known as SIMPLE (NCT04292899), showed that a shorter, five-day course of treatment with remdesivir leads to similar improvements in clinical status as a 10-day course of treatment in patients hospitalized with severe COVID-19. The open-label trial is  testing the effects of two dosing durations (five days and 10 days) of the experimental antiviral.

The European Medicines Agency also began a rolling review of remdesivir for COVID-19, with the goal of shortening the review time of the treatment from months to weeks.

The FDA granted emergency use authorization to a new antibody test for COVID-19. The test, developed by Roche, is called Elecsys. It is able to determine with 100% sensitivity and 99.8% specificity whether a person has been exposed to SARS-CoV-2 in the past and developed antibodies against the virus.

The first participants have been dosed in a Phase 1/2 trial in the U.S. that is testing four mRNA vaccine candidates being jointly developed by BioNTech and Pfizer against COVID-19. The first part of the trial is a dose escalation stage that is enrolling up to 360 healthy individuals. The BNT162 vaccine program also includes a similar trial in Germany, which completed dosing of its first group last week.

Massachusetts General Hospital is conducting a clinical study to assess the potential efficacy of inhaled nitric oxide to reverse hypoxemia (abnormally low oxygen levels in the blood) in patients with severe COVID-19. Mallinckrodt Pharmaceuticals is providing both funding and INOmax — nitric oxide gas for inhalation — for the study.

Patients are being enrolled in a Phase 2 trial at Beaumont Hospital in Royal Oak, Michigan, to test a combination of naltrexone and ketamine for treating COVID-19. Researchers will assess whether reducing inflammation with the combo therapy may lessen the severity of COVID-19 symptoms.

AstraZeneca and the University of Oxford are collaborating on developing a potential vaccine against COVID-19 to be developed and distributed globally. The potential vaccine, called ChAdOx1 nCoV-19, is being developed by the University of Oxford and will be manufactured and distributed by AstraZeneca.

April 29, 2020

German regulatory authority Paul-Ehrlich-Institut approved a Phase 1/2 clinical trial for BioNTech and Pfizer‘s BNT162 vaccine program, which is testing four mRNA vaccine candidates to prevent COVID-19. In the first phase of the trial, researchers will test the vaccines in 200 healthy volunteers ages 18 to 55 to determine the optimal dose. The second part will include participants at a higher risk of severe COVID-19.

Asthma medication MN-166 (ibudilast) will be tested in a clinical trial to assess its potential in treating acute respiratory distress syndrome caused by COVID-19. The trial is a collaboration between Yale University and pharmaceutical company MedicNova.

A trial called STOP-COVID19 is expected to start recruiting up to 300 hospitalized patients with COVID-19 in the U.K. in May to test the experimental treatment brensocatib. Insmed, which is developing the treatment for bronchiectasis and other inflammatory diseases, will provide funding and the medication for the trial, which is sponsored by the University of Dundee.

A new trial funded by Amazon and run by Columbia University will assess whether plasma (the liquid portion of the blood devoid of cells) obtained from COVID-19 survivors can be used to prevent SARS-CoV-2 infections or treat COVID-19. The trial aims to recruit 450 people who have been in close contact with COVID-19 patients such as healthcare workers as well as intensive care unit patients.

Astra Zeneca will test the diabetes treatment Farxiga (dapagliflozin) in a trial to assess its potential to decrease the risk of death from serious complications and organ failure in COVID-19 patients. The trial, which is a collaboration with Saint Luke’s Mid America Heart Institute, will enroll 900 participants in the U.S. and European countries that are experiencing high rates of COVID-19 cases.

An experimental treatment by Vivacelle Bio will be made available for compassionate use in COVID-19 patients. The experimental treatment, called VBI-S, is currently being tested in a Phase 2 trial (NCT04257136) people with reduced blood circulation due to sepsis.

Genalyte launched a COVID-19 test to detect antibodies produced by the body against SARS-CoV-2. Cleared by the FDA, the test runs on Genalyte’s Maverick platform.

Quest Diagnostics started offering an antibody testing service for COVID-19 on blood samples. The antibody test, intended for healthcare providers, can determine whether a person has antibodies in their blood against SARS-CoV-2, meaning they have been exposed to the virus and may have some level of immunity against it.

April 22, 2020

Biogen, Broad Institute, and Partners HealthCare are launching a consortium to build and share a COVID-19 biobank. The biobank will contain blood samples of Biogen employees willing to participate in the project who contracted and have recovered from COVID-19. People identified as close contacts of those individuals are also eligible to participate regardless of whether they were confirmed to have COVID-19. The biobank will help scientists understand why some people infected with SARS-CoV-2 become seriously ill while others do not even show any symptoms. A better understanding of the biology of the virus and the response the human body has to it will help speed the quest for potential vaccines and treatments.

Alexion is planning a Phase 3 trial testing Ultomiris (ravulizumab-cwvz) for treating severe COVID-19. The global trial will include approximately 270 hospitalized patients who have severe pneumonia or acute respiratory distress syndrome. Ultomiris is FDA-approved for paroxysmal nocturnal hemoglobinuria and atypical hemolytic uremic syndrome (aHUS).

In the coming weeks, Novartis is planning to start enrollment for its randomized Phase 3 trial testing hydroxychloroquine in hospitalized COVID-19 patients. An estimated 440 patients will be recruited across more than a dozen U.S. sites.

Sinovac has launched a randomized Phase 1 trial in China to test its vaccine candidate against COVID-19. The first group of an estimated total of 144 healthy adults have already been given the first dose of two doses of the experimental vaccine.

The FDA authorized a saliva test for emergency use to diagnose COVID-19. The test was developed by Rutgers University in collaboration with other groups. The test can only be used in a healthcare setting and is not available to purchase for home testing.

LabCorp has received emergency use authorization from the FDA for the first diagnostic test using samples collected from people at home. The at-home kit includes a special cotton swab to collect a sample from the individual’s nose. The sample is then mailed in an insulated package to a LabCorp lab. The products contained in the LabCorp collection kit are the only ones authorized for at-home use at this time.

April 15, 2020

Biohaven Pharmaceuticals will soon start a Phase 2 clinical trial to test intranasal vazegepant in treating lung complications caused by COVID-19. The trial will run in collaboration with Thomas Jefferson University and other institutions.

The FDA has cleared a Phase 2 trial that will test the safety and efficacy of Hope Biosciences’ adipose-derived mesenchymal stem cells to provide immune support against COVID-19. The trial will enroll an estimated 100 front-line healthcare workers and first responders and will test three doses of cells over 14 weeks.

Vaxil has completed the first preclinical experiment testing its COVID-19 vaccine candidate. According to the results, the vaccine candidate showed a favorable immune response in healthy donor blood cells. The company has now begun the next set of experiments to better understand the immune responses and determine dosing, with additional experiments planned.

Sanofi and GlaxoSmithKline are partnering on developing an adjuvanted COVID-19 vaccine. Sanofi is providing its S-protein COVID-19 antigen, based on a recombinant RNA technology that created an exact match to proteins found on the surface of the virus. GSK will contribute its pandemic adjuvant technology, which is intended to boost the immune response and may lead to a stronger and longer-lasting effect than the vaccine alone. The companies are aiming to launch a Phase 1 trial in the second half of this year.

April 8, 2020

The FDA issued an emergency use authorization for an antibody test for COVID-19. Developed by Cellex, the test looks for antibodies in the blood that the body produces against SARS-CoV-2 instead of the virus itself.

Thiolanox (high-dose inhaled nitric oxide therapy) can now be tested in patients infected with SARS-CoV02 as part of a Phase 2 clinical trial (NCT03331445) that began in 2017 to assess its effects in treating difficult lung infections. Mallinckrodt e Novoteris, developers of Thialonax, announced on April 1 that their joint pilot trial was cleared by the Therapeutic Products Directorate of Health Canada. The trial will now be able to recruit participants infected with SARS-CoV-2 at Vancouver Coastal Health Authority facilities to test the therapy’s safety and effectiveness in treating COVID-19.

The FDA approved a randomized, double-blind, placebo-controlled Phase 3 trial (NCT04320615) to evaluate the safety and efficacy of Actemra (tocilizumab) plus standard of care in hospitalized adults with severe COVID-19 pneumonia. Actemra is an anti-rheumatoid medication by Genentech that is also being evaluated in a number of other trials as a potential treatment for COVID-19.

A Phase 3 trial called RUXCOVID is awaiting FDA clearance to evaluate the safety and efficacy of ruxolitinib in COVID-19-associated cytokine storm. The medication was developed by Incyte and is sold under the brand-name Jakafi for polycythemia vera, myelofibrosis, e acute graft-versus-host disease. Two more trials will test ruxolitinib in treating severe acute respiratory syndrome (SARS) caused by COVID-19 (NCT04334044) and COVID-19 pneumonia (NCT04331665). The trials will take place in Mexico and in Canada respectively, but are not yet recruiting patients.

Researchers are working on a new RNA-based immunotherapy to treat COVID-19. The potential treatment would be inhaled by patients and produce therapeutic antibodies in the lungs. Neurimmune e Ethris are hoping to start trials testing the potential treatment by the end of the year.

Preclinical studies have begun in Australia testing potential vaccines against COVID-19. Run by Australia’s Commonwealth Scientific and Industrial Research Organization, these studies are also testing the best way to administer the vaccine.

The Regulatory Affairs Professionals Society has released a COVID-19 Therapeutics Tracker. The tracker is updated weekly with details about new treatment candidates for COVID-19.

April 1, 2020

Several tests for diagnosing COVID-19 have now been granted emergency use authorization (EUA) from the FDA. As of March 31, the Advanced Medical Technology Association estimated that 17 tests had received EUAs, with more in the works. The same day, Bodysphere announced it was rolling out a test that returned results within two minutes, saying it was granted an EUA, but the FDA later refuted that claim. The test at this point has not received any FDA authorization.

The FDA issued a warning last week that it has not authorized any test for people to use at home for COVID-19 and that people should be aware of such fraudulent tests. It also provided a list of fraudulent COVID-19 products including those that claim to prevent or treat the disease.

The agency also announced the creation of an emergency program called the Coronavirus Treatment Acceleration Program to assist in the development of treatments for COVID-19. According to the FDA, as of March 31, it is reviewing 10 therapies already in trials and 15 others in preclinical stages.

Sandoz’s malaria treatment hydroxychloroquine sulfate and Bayer Pharmaceuticals’ chloroquine phosphate have been granted an EUA by the FDA for the treatment of COVID-19. Both companies have donated supplies of the medications to the U.S. Department of Health and Human Services for use. Although clinical trials are needed to prove their efficacy in treating COVID-19, these therapies have shown some benefit in the lab and clinic, according to anecdotal evidence.

Among the trials recently launched for COVID-19 are a global Phase 2/3 trial (NCT04315298) testing rheumatoid arthritis treatment Kevzara (sarilumab) and a U.K.-based Phase 2 trial testing antiviral SNG001, an inhaled formulation of interferon-beta-1a. The first patients have already been treated in both trials. Another Phase 2/3 trial (NCT04315298) testing Kevzara is recruiting an estimated 400 participants in the U.S.

A Phase 2 trial (NCT04311697), taking place in New York and Haifa, Israel, will test aviptadil for the treatment of COVID-19-associated acute respiratory distress syndrome.

Johnson & Johnson announced plans to start a Phase 1 trial by September to test its vaccine candidate Ad26 SARS-CoV-2 against COVID-19. If the trial is successful, the first batch of the vaccine could be available in early 2021 for emergency use, according to the company.

March 27, 2020

Il CDC has developed a diagnostic panel for use by CDC-qualified laboratories in the U.S. and made available under an emergency use authorization (EUA) from the FDA

Other new tests include Roche Diagnostics’ cobas SARS-CoV-2 test, also granted an EUA, and the U.S. Department of Health and Human Services is funding the development of two other diagnostic tests that can detect the presence of SARS-CoV-2 within one hour.

Il National Institute of Allergy and Infectious Diseases is sponsoring a randomized, controlled Phase 2 trial in the U.S. to evaluate the safety and efficacy of the broad-spectrum anti-viral treatment remdesivir di Gilead Sciences to treat the disease. Gilead has also launched two global Phase 3 trials to evaluate remdesivir’s safety and efficacy in adults with COVID-19.

Other treatments being investigated for COVID-19 include a novel mRNA-1273 nanoparticle-encapsulated vaccine (NCT04283461), thalidomide (NCT04273581), sildenafil (NCT04304313), eculizumab (NCT04288713), recombinant human interferon-alpha 1 beta (NCT04293887), bevacizumab (NCT04305106), and antibodies from cured patients (NCT04264858), among others.

Researchers are also looking at new synthetic biology approaches by using self-assembling nanoparticles coated with viral antigens that can precisely target SARS-CoV-2. This approach can potentially overcome some of the limitations of conventional vaccines such as short shelf-life and viral evolution.

What is COVID-19?

COVID-19, short for coronavirus disease 2019, is an infection caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). SARS-CoV-2 is a newly identified pathogen that has not previously been seen in humans and is highly contagious. Though it belongs to the same category of viruses as SARS coronavirus (SARS-CoV) and influenza viruses, SARS-CoV-2 is a different strain with its own characteristics.

COVID-19 was first reported in Wuhan, China, in December 2019, and the outbreak has spread quickly across the world, prompting the World Health Organization (WHO) to declare COVID-19 a pandemic.

How does COVID-19 spread?

Because COVID-19 is a new virus, nobody has prior immunity to it, meaning the entire human population is prone to infection.

SARS-CoV-2 primarily spreads via respiratory droplets when people cough or sneeze. Scientists have yet to understand how easily and sustainably the disease can spread among people. Based on available evidence, researchers do not think that airborne spread is a major transmission route.

Individuals over age 60 are also at the highest risk of developing a severe case of COVID-19, while children do not seem to be at a higher risk than adults.

What are the symptoms of COVID-19?

Common symptoms of COVID-19 begin two to 14 days after exposure. They include fever, tiredness, and dry cough. Other symptoms include sputum production, shortness of breath, sore throat, headache, myalgia (muscle pain) or arthralgia (joint pain), chills, vomiting, and nasal congestion. Less frequent symptoms include diarrea, hemoptysis (coughing up blood from the respiratory tract), and conjunctival congestion.

Most of these symptoms are usually mild, and about 80% of people who get the virus will typically recover without needing any special treatment. However, about 1 in 6 patients become seriously ill and develop breathing difficulties.

What general preventive measures should people take?

The following simple preventive measures can help minimize the spread of COVID-19:

  • Wash your hands often with soap, lathering both the front and the back of the hands and fingers for at least 15 to 20 seconds. If soap is not available, use a hand sanitizer that contains at least 60% alcohol. The European Centre for Disease Prevention and Control produced a poster detailing effective handwashing.
  • Avoid close contact with someone who is ill. (Maintain a distance of at least 6 feet, or 1.8 meters).
  • Stay at home if you are sick.
  • Use a tissue to cover your mouth and nose if you cough or sneeze and dispose of it properly afterward.
  • Disinfect surfaces and objects you touch frequently.
  • Avoid touching your eyes, nose, and mouth with unwashed hands.

The U.S. Centers for Disease Control (CDC) does not recommend that healthy people wear a face mask.

What extra precautions should patients with AADC deficiency take?

There is no indication that AADC deficiency makes patients more vulnerable to COVID-19. However, people living with chronic diseases may be more likely to develop a more serious infection from COVID-19.

These patients should, therefore, exercise caution and take necessary measures to protect themselves, as advised by the CDC. In addition to the general preventive measures listed above, they should avoid crowds and stay home as much as possible.

Patients should see their healthcare providers if any COVID-19-like symptoms are present.

Advice for family members and caregivers

Family members and caregivers of people with chronic diseases such as AADC deficiency should take appropriate precautions and take extra care to avoid bringing COVID-19 home. They should constantly monitor patients and stock medicines and other necessary supplies that can last for several weeks. Storing extra non-perishable food can help minimize trips to the grocery store.

What should sick individuals do?

If symptoms are present and a COVID-19 diagnosis is confirmed, patients should follow these steps to prevent the spread of the infection:

  • Stay at home, preferably in a separate room not shared with others, and isolate themselves, with the exception of getting medical care.
  • Avoid public areas and public transport.
  • Limit contact with pets and animals.
  • Avoid sharing personal items.
  • Cover coughs and sneezes with tissues and dispose of them properly.
  • Sanitize hands regularly.
  • Disinfect surfaces such as phones, keyboards, toilets, and tables.

People should call ahead before visiting the hospital for an appointment. This way, the hospital can take necessary steps to prevent the spread of the infection.

Patients who have confirmed COVID-19 should wear face masks when going out. The WHO’s website has a resource explaining the proper use of a face mask.

What tests are available?

Many tests for the detection of COVID-19 have been made available under the FDA’s emergency use authorization, including rapid tests that are being developed to detect the presence of the virus within minutes.

The Foundation for Innovative New Diagnostics provides an up-to-date list of different manual and automated tests that are available or currently in development.

Is there a treatment?

There are currently no vaccines available for human coronaviruses including COVID-19. This makes the prevention and containment of the virus very important.

Oxygen therapy is the major treatment intervention for patients with severe disease. Mechanical ventilation may be necessary in cases of respiratory failure.

Are there new treatments in the pipeline?

Several clinical trials have been launched or are being planned to test a variety of potential treatments and vaccines for COVID-19. A complete list of all ongoing clinical trials pertaining to the virus is available here.

***

AADC News is strictly a news and information website about the disease. It does not provide medical advice, diagnosis, or treatment. This content is not intended to be a substitute for professional medical advice, diagnosis, or treatment. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a medical condition. Never disregard professional medical advice or delay in seeking it because of something you have read on this website.

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Özge has a MSc. in Molecular Genetics from the University of Leicester and a PhD in Developmental Biology from Queen Mary University of London. She worked as a Post-doctoral Research Associate at the University of Leicester for six years in the field of Behavioural Neurology before moving into science communication. She worked as the Research Communication Officer at a London based charity for almost two years.

Psorilax:Aumentare |crema che ti libera da psoriasi

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Psorilax: prezzo, funziona, recensioni, opinioni, come si usa

Descrizione di questa immagine, anche commentata di seguito

Psoriasi a placche nella parte posteriore.

ICPC-2 S91Visualizza e modifica i dati su Wikidata
ICD-10

L40

ICD-9

696

MIM

177900

DiseasesDB

10895

MedlinePlus

000.434

eMedicine 1943419, 1108072, 1107850, 1107949, 1108220, 331037 e 394752Visualizza e modifica i dati su Wikidata
eMedicine

emerg / 489 derm / 365, derm / 361, derm / 363, derm / 366, derm / 918, radio / 578, pmr / 120

MeSH

D011565

trattamento Terapia della luce ultravioletta (in)Visualizza e modifica i dati su Wikidata
Farmaco Metotrexato, farmaco antinfiammatorio non steroideo, tazarotene (in)etil fumarato (d), desoximetasone (in), apremilast, tacalcitol (in), calcipotriolo e desonideVisualizza e modifica i dati su Wikidata

Wikipedia non fornisce consulenza medica Avviso medico

il psoriasi è una malattia infiammatoria sistemica e cronica immuno-mediata, che colpisce principalmente la pelle(1) ma anche altri organi (articolazioni, sistema cardiovascolare, mucose …). Questa malattia colpisce circa il 3-5% della popolazione europea (2). È accompagnato da infiammazioni simmetriche del derma e dell'epidermide nonché da un eccessivo rinnovamento delle cellule della pelle. A causa delle sue origini multifattoriali, questa condizione è polimorfica nell'aspetto clinico e ha una grande varietà di posizioni. Di eziologia incerta, probabilmente multigene, non è contagiosa e non può essere curata. I trattamenti noti consentono solo di rallentare o ridurre l'infiammazione associata.

La psoriasi presenta un'ampia varietà di fenotipi perché deriva da una combinazione multifattoriale complessa e varia tra meccanismi immunologici, un profilo poligenico e anomalie cellulari della pelle. (3).

Questa dermatosi si sviluppa cronicamente con ricadute intervallate da periodi di remissione di durata variabile (a volte per tutta la vita). L'intensità delle recidive e delle remissioni varia in base a molti fattori (esposizione al sole, stress, pelle danneggiata, ecc.). Le aree sbiancate non lasciano cicatrici e sono solo così in superficie. In realtà mantengono un terreno patologico.

Inoltre non può mai esserci una remissione (senza trattamenti farmacologici): una volta che ha raggiunto un certo livello di evoluzione molto relativa a seconda dell'individuo, la psoriasi si stabilizza e può quindi essere mantenuta per anni o per tutta la vita.

da Fenomeno di Koebner, è probabile che tutti i tipi di psoriasi si diffondano in aree che hanno subito un attacco fisico o chimico (cicatrici, sfregamenti, ustioni, ecc.), la soglia di tolleranza è diventata piuttosto bassa.

Contrariamente alle attuali conoscenze, sette psoriasi su 10 segnalano prurito (prurito) (4). Ma è difficile sapere se non è l'effetto di un affetto secondario a causa dell'indebolimento delle barriere naturali della pelle (allergie, ecc.) O anche di una causa psicologica. Questi pruriti mantengono l'infiammazione all'effetto Koebner.

I diversi tipi(cambiamento | cambia codice)

  • Psoriasi a placche : Chiamato anche psoriasi vulgaris, è la forma più comune di psoriasi (oltre il 90% dei casi(5)) che ha dato il nome alla malattia: “grandi squame”. Nella sua forma classica, la placca elementare si presenta sotto forma di lesioni rosse, eritema, irritate, squamose e infiltrate. Le piastre hanno una distribuzione approssimativamente simmetrica. Sebbene possano riguardare qualsiasi area, si trovano preferibilmente nella regione dei gomiti, delle ginocchia, del cuoio capelluto, delle unghie, del condotto uditivo, della regione lombare o peri-ombelicale(6). Quando le squame si staccano, lasciano aperta la pelle, a volte sanguinante.
  • La psoriasi cade nella parte posteriore.

    Gocce di psoriasi (7): Psoriasi gotta (o psoriasi guttata), come suggerisce il nome, è caratterizzato da una dispersione di piccole gocce di psoriasi in tutto il corpo. Non si osserva alcuna placca se non gocce che hanno il vantaggio, per le loro dimensioni ridotte, di “sbiancarsi” più velocemente e quindi di rimanere “irritanti” per breve tempo. Si trovano su tutte le aree di attrito: parte inferiore dell'addome, parte bassa della schiena (taglia dei pantaloni) avambraccio, circonferenza del torace (reggiseno) ma anche pelo e padiglione esterno dell'orecchio.

  • Psoriasi pustolosa localizzata : Questa dermatosi molto meno frequente riguarda circa il 10% della psoriasi. È stato a lungo considerato distinto dalla psoriasi a causa delle sue diverse manifestazioni cliniche e dell'impossibilità di trovare un comune denominatore genetico, in particolare il PSOR1 a cui è estraneo. Tuttavia, sebbene si verifichi spesso da solo, è sporadicamente associato alla psoriasi comune. Le somiglianze istologiche (esocitosi polinucleare, pustola spongiforme di Kogoj-Lapierre) finiscono per convincere i dermatologi a classificarlo in particolare la psoriasi. Clinicamente questa psoriasi è caratterizzata dall'apparizione di pustole piatte, da bianche a giallastre, amicrobiche, incorporate nell'epidermide e che tendono a diffondersi dando l'impressione di coalescenza (raggruppamento).

    Psoriasi pustolosa localizzata e leucoderma. Le pustole si diffondono e si fondono. Sono costituiti da un infiltrato di leucociti secco che, per effetto dell'accumulo, bombarda la pelle e la rende glabra. Questi raramente colpiscono la superficie posteriore delle dita.

    Durante le eruzioni, queste placche diventano marroni e la pelle si asciuga quindi si sbriciola o lacrime, lasciando il derma dolorosamente nudo. È anche associato a parestesia (formicolio e sensazione di bruciore). Simmetrico nella distribuzione, si trova più spesso alle estremità degli arti dove costituisce la psoriasi palmoplantare pustolosa (PPPP)(8). Tuttavia, possono essere interessate altre aree del corpo, in particolare durante l'assunzione di farmaci. La PPPP riguarda le donne più spesso degli uomini e inizia preferibilmente tra i 50 e i 60 anni(8). Colpisce generalmente i palmi delle mani, l'eminenza del piede e l'arco, più raramente la parte anteriore delle dita delle mani e dei piedi (acropustulosi). Nella fase acuta parliamo di batteridi pustolosi di Andrews durante i quali sono interessati tutti i piedi e le mani, inclusi i lati posteriori. Questa condizione è spesso legata alla sensibilizzazione a causa di un lontano focus dell'infezione. Scompare con esso dopo alcune settimane.

  • Psoriasi pustolosa generalizzata (da Von Zumbusch): la psoriasi volgare può, in rari casi, generalizzare ed essere pericolosa per la vita.
  • Psoriasi inversa o piega della psoriasi : Placca rossa brillante, ben limitata, lucida, liscia, con scaglietti piccoli o nulli. Affetto delle grandi pieghe (inter-gluteo, straripante inguinale nell'area genitale, sotto mammaria, più raramente poplitea e ascellare) e meno spesso piccole pieghe (ombelico)
  • Psoriasi eritrodermica : Colpisce quasi l'intero sistema tegumentario, che è rosso, a volte bagnato, edematoso, coperto da squame sottili. Ci sono segni generali (febbre, anoressia), a volte linfoadenopatia. I rischi sono: infezioni secondarie, disturbi idroelettrolitici, disidratazione. Nella maggior parte dei casi è necessario il ricovero in ospedale.
  • Psoriasi ungueale : Rappresenta la metà dei casi di psoriasi(5). Solo l'1-5% è solo non ufficiale. In questo caso possono essere confusi con una micosi (diagnosi più difficile). Esistono due tipi di sintomi a seconda della posizione: se la matrice è interessata, l'unghia si deforma in increspature o becchi chiamati ditali; Se il letto ungueale è interessato, l'unghia cambia colore (giallo, arancione), si ispessisce (ipercheratosi) o si stacca (onicolisi).

  • Psoriasi blaschko-lineare : La distribuzione della psoriasi avviene lungo linee cellulari mutanti, comparsa di embriogenesi (9). Questa psoriasi a mosaico evidenzia il probabile ruolo di un'anomalia cutanea scarsamente supportata dall'immunità. Inoltre, questa psoriasi a volte appare in risposta a cure mediche.(10).
  • Psoriasi delle mucose : La lingua può essere colpita assumendo un aspetto rialzato con aree ispessite e biancastre localizzate. Anche la mucosa vaginale può essere colpita. Le macchie rosse di solito non si sfaldano e talvolta sono dolorose durante il rapporto. Sono favorevoli alle lesioni che possono bruciare o prudere.
  • sebopsoriasis :
  • Psoriasi ipercheratotica :
  • Psoriasi delle mucose :
  • Psoriasi da pannolino :
  • Psoriasi infantile e infantile :
  • Artrite psoriasica : Infiammazione coniugata che produce sintomi di artrite nei pazienti che hanno sviluppato o svilupperanno la psoriasi. Chiamata anche artrite psoriasica, colpisce circa il 5% (ma la cifra può raggiungere il 25% in alcune pubblicazioni(11)) psoriasico, ed è generalmente associato a lesioni cutanee (che, raramente, possono iniziare dopo i reumatismi). È un reumatismo infiammatorio cronico, deformante, che può essere molto invalidante, di cui sono descritte due forme principali, che possono essere associate:
    • Reumatismi assiali: aspetto molto vicino alla pelvispondilite reumatica: SPA (collo, schiena, sacroiliaco) e si verifica più spesso negli uomini che portano HLA-B27.
    • Reumatismo periferico: aspetto vicino all'artrite reumatoide, con tuttavia una predilezione per l'interfalangea distale (la pelle delle dita, le unghie, sono spesso colpite dalla psoriasi). Nessuna associazione con HLA-B27.

Alcune forme possono svilupparsi a seguito di traumi articolari.

La psoriasi è una malattia complessa. La ricerca scientifica non ha isolato una singola causa ma ha evidenziato i fattori di rischio responsabili della suscettibilità o della vulnerabilità. Sebbene i meccanismi intimi dell'infiammazione che caratterizzano la psoriasi siano sempre più noti, l'effetto fondante del fenomeno rimane poco chiaro. I fattori di rischio, molto numerosi, sono di 2 nature: una strutturale di ordine genetico, l'altra ambientale di ordine infettivo, psico-fisiologico. Sembra che siano le combinazioni di questi fattori poligenici e ambientali che scatenano la malattia.

Una predisposizione genetica(cambiamento | cambia codice)

La psoriasi ha alcuni componenti genetici(12) perché quasi il 30% delle persone colpite ha un familiare affetto dalla stessa malattia(13).
La presenza di molti leucociti nel derma suggerisce l'importante ruolo svolto dal sistema immunitario. L'ipotesi di un meccanismo di autoimmunità è stata mantenuta(14).

Tra i molti geni identificati come potenziali marker di rischio c'è il PSORS (PSORiasis Susceptibility) :

Vari fattori influenzanti(cambiamento | cambia codice)

Questa malattia multigenica ha anche un'alta suscettibilità ambientale. Il che rende difficile chiarire. I fattori di influenza sono numerosi, endogeni ed esogeni. La maggior parte peggiora i sintomi della psoriasi. Alcuni sono identificati come i trigger per i primi razzi.

  • Anomalie cutanee primarie: i cheratinociti psoriasici hanno caratteristiche funzionali diverse da quelle di un soggetto sano (3) ,(2).
  • Stress: l'anamnesi effettuata con i pazienti mostra che i primi effetti visibili della psoriasi seguono uno stress significativo, uno shock emotivo o uno shock emotivo.
  • Infezione: i casi di psoriasi gotta nei bambini associati a infezioni da streptococco sono riportati nella letteratura scientifica(20). Altri studi(21) evocare la possibile influenza dei retrovirus nella patogenesi della psoriasi.
  • Sostanza tossica: l'eccessivo consumo di alcol è un fattore che aggrava la psoriasi.
  • Iatrogenesi: paradossalmente, sempre più persone trattate con anti-TNF-alfa stanno innescando nuove placche di psoriasi o manifestando un deterioramento di vecchie placche(22). Nel 2011 sono stati colpiti fino al 10% delle persone trattate(22). Altri farmaci a volte esacerbano la psoriasi, ma la loro sospensione deve essere discussa caso per caso, che può comportare altri rischi, in particolare cardiovascolari. Questi sono essenzialmente quelli della classe dei beta-bloccanti. Altre molecole sono state segnalate come potenzialmente aggravanti, ma con un rischio inferiore. Questi sono i sartani(23) ed enalapril(rif. desiderato).
  • Ormoni: durante la gravidanza, si osserva generalmente una diminuzione dei breakout con peggioramento a causa di ciò. Il meccanismo invocato è quello di un'immunomodulazione dagli alti livelli di progesterone ed estrogeni che portano a una stimolazione dell'immunità dipendente dai linfociti B ma a una diminuzione dell'attività immunitaria dei linfociti T. Il progesterone è riconosciuto come avere un ruolo immunomodulatore chiave durante la gravidanza(24).
  • Microbiologico: recenti ricerche evidenziano il piccolo numero di alcuni batteri cosiddetti “benefici” nel microbiota intestinale delle persone con artrite psoriasica(25).
  • Il cibo.

Contrariamente alla sua definizione iniziale, la psoriasi non dovrebbe più essere considerata solo come una condizione della pelle, ma come una malattia sistemica che diffonde la sua patogenesi a lungo termine a tutti gli organi del corpo umano. I segni che compaiono sulla pelle sono in realtà solo una parte di un problema di fondo. Oltre alla pelle e alle appendici, può interessare le articolazioni, il sistema cardiovascolare, le mucose(26).

  • Psicosociale: l'effetto sgradevole che ostacola il soggetto nella sua vita quotidiana, può essere particolarmente spiacevole anche attraverso un intenso prurito. Il graffio delle lesioni psoriasiche porta allo spotting emorragico chiamato segno di Auspitz o segno di rugiada sanguinante studiato dal dermatologo Heinrich Auspitz(27)
  • Sessuale: quando la psoriasi si diffonde sui genitali, le relazioni sessuali diventano più delicate perché diventano molto dolorose.
  • Cardiovascolare: i portatori di psoriasi hanno un rischio maggiore di avere un infarto del miocardio, tanto più che il coinvolgimento è diffuso(28). Le forme gravi hanno una mortalità cardiovascolare più elevata(29). Ciò può essere correlato a un disturbo del metabolismo lipidico osservato in pazienti con psoriasi(30) e con infiammazione cronica. Esiste anche una correlazione tra la gravità della malattia della pelle e il rischio di avere stenosi aortica(31).
  • Disturbi del metabolismo lipidico;
  • Danno renale: aumenta anche il rischio di sviluppare a insufficienza renale(32).
  • Articolazioni: come le vittime dell'artrite reumatoide, diventano anche più sensibili al dolore, a causa di una nocicezione rafforzata da una sorta di effetto di “sensibilizzazione”.(33)

L'epidermide si rinnova troppo rapidamente, in soli 4-6 giorni, invece delle solite tre settimane, che causa infiammazione localizzata. Le cellule epidermiche si accumulano sulla superficie della pelle e formano uno strato di forfora bianca chiamata dander. Perfettamente innocui, hanno lo svantaggio di essere antiestetici.

L'esame microscopico di un campione di pelle colpita è di scarsa utilità nella pratica quotidiana, essendo spesso più evidente l'esame clinico.
Questo esame mostra un aumento dello spessore dell'epidermide, la presenza di numerosi vasi sanguigni particolarmente tortuosi nel derma con infiltrazioni in quest'ultimo da parte dei leucociti.

Nella pelle non affetta, l'esame al microscopio è rigorosamente normale.

Non è nota alcuna cura, anche se si consiglia vivamente di esporre al sole le aree colpite dalla psoriasi. Un trattamento proposto consente solo di controllare l'evoluzione della malattia, consentendo una regressione transitoria più o meno completa delle lesioni. Il trattamento è adattato in base alla gravità e all'impatto sulla qualità della vita dei pazienti.

Trattamento locale(cambiamento | cambia codice)

Il trattamento locale consiste nell'applicare una crema nell'area della psoriasi.
I corticosteroidi hanno un effetto favorevole sulla psoriasi, purtroppo spesso le placche ritornano non appena il trattamento viene interrotto. Quest'ultimo genera anche una forma di intorpidimento, che richiede un aumento delle dosi nel tempo. Inoltre, l'effetto non è più solo locale se questi unguenti vengono applicati su aree di grandi dimensioni. Questa forma di trattamento dovrebbe quindi essere limitata a forme acute o altamente sgradevoli, per un breve periodo e su un'area limitata.

L'esposizione al sole ha un chiaro ruolo protettivo. Il calcipotriolo (calcipotriene) è un derivato di vitamina D3. Normalmente, quest'ultimo viene sintetizzato durante l'esposizione della pelle alla luce ultravioletta solare. Questo è quindi un sostituto per questa esposizione (o puvatherapy). Tuttavia, la quantità massima applicabile è limitata perché, a dosi elevate, il calcipotriolo diventa tossico.
Il tazarotene è un derivato della vitamina A disponibile in unguento. La sua tolleranza sarebbe tuttavia inferiore al calcipotriolo(34).

I tar (incluso l'olio di cade) erano precedentemente usati frequentemente nell'applicazione sulla psoriasi ma erano scomodi perché erano particolarmente sporchi.
Il Dithranol è un derivato del catrame. Il dithranol ha una certa efficacia, soprattutto in combinazione con altri trattamenti, ma a volte è irritante e soprattutto scomodo (molto “colorazione”), che ne limita l'uso.

Altri trattamenti includono acido salicilico, bagni, creme idratanti per la pelle.
Questi trattamenti locali possono eventualmente essere combinati.

fototerapia(cambiamento | cambia codice)

L'esposizione al sole molto spesso ha un'influenza favorevole sulla psoriasi(35),(36). Tuttavia, nel 10% dei casi, questa esposizione sarà effettivamente dannosa.(rif. richiesto). Il soggetto dovrebbe quindi evitare il sole o almeno evitare di essere esposto direttamente ai suoi raggi.

La fototerapia alla luce del sole è stata a lungo praticata per il trattamento della psoriasi. La luce UV a una lunghezza d'onda compresa tra 311 e 313 nm è la più efficace ed è per questo motivo che i produttori hanno sviluppato lampade speciali per questo scopo. Il tempo di esposizione deve essere controllato per evitare il sovradosaggio e le ustioni della pelle. Le lampade UVB devono quindi avere un timer che assicuri che il dispositivo si arresti alla fine del trattamento. La quantità di luce necessaria dipende dal tipo di pelle. Il numero di tumori correlati al trattamento è basso. È stato dimostrato che la luce UVB a banda stretta ha un'efficacia paragonabile al trattamento PUVA. L'efficienza della luce a LED blu a una lunghezza d'onda di 453 nm è stata recentemente dimostrata(37),(38). Questa luce blu atossica e priva di UV è ora disponibile come dispositivo medico portatile. La durata del trattamento è determinata da un timer. Questo trattamento di fototerapia non contiene sostanze chimiche o ingredienti attivi.

Si raccomanda anche la fototerapia a raggi ultravioletti B (UVB), che può essere combinata con altre terapie.

Uno dei principali modi di azione della terapia UVB a banda stretta è che provoca danni al DNA sotto forma di dimeri di pirimidina. Questo tipo di fototerapia è interessante per il trattamento della psoriasi perché la formazione di questi dimeri interferisce con il ciclo cellulare e lo interrompe. Questa interruzione del ciclo cellulare indotta dalle radiazioni UVB a banda stretta combatte la rapida divisione delle cellule della pelle, caratteristica della psoriasi. L'attività di molte cellule immunitarie della pelle è anche soppressa dalla fototerapia UVB a banda stretta(40),(41). L'effetto collaterale a breve termine più comune di questa forma di fototerapia è la comparsa di arrossamenti sulla pelle; meno comuni sono prurito, comparsa di vesciche, irritazione oculare sotto forma di infiammazione della congiuntiva o della cornea o herpes labiale a causa della riattivazione del virus dell'herpes a contorno labbra. La protezione degli occhi è generalmente prescritta durante le sessioni di fototerapia.

In tutti i casi, la terapia a raggi ultravioletti (A o B) deve essere eseguita sotto controllo medico. Porta a una soglia di tolleranza variabile da un individuo all'altro che è necessario non superare. Senza questo, il paziente è esposto all'eliodermia e i rischi – bassi – di tumori della pelle (epitelioma, melanomi), rischiano ancora di più in quanto un paziente affetto da psoriasi ha controlli dermatologici molto più di un paziente medio. , che consente di rilevare l'insorgenza precoce della neoplasia.

La luce blu si è dimostrata efficace anche per il trattamento della psoriasi(41),(42). Gli studi hanno dimostrato che la luce blu riduce l'accelerazione della produzione di cellule cheratinocitiche e ha anche proprietà antinfiammatorie. La luce blu fa parte dello spettro della luce visibile ed è quindi priva di UV. Questa terapia non contiene inoltre sostanze chimiche o principi attivi. Durante questo studio clinico di 4 mesi non sono stati osservati effetti collaterali, tuttavia mancano dati di follow-up a lungo termine.

Terapia sistemica(cambiamento | cambia codice)

Per le forme più gravi di psoriasi, i medici possono prescrivere trattamenti per via orale (compressa o capsula) o per iniezione. Questi trattamenti sono chiamati sistemici perché si ritiene che i farmaci si diffondano in tutto il corpo. A seconda del trattamento e del suo modo di agire, potrebbero esserci più o meno effetti collaterali(43).

I trattamenti sistemici sono classificati in due sottocategorie: sistemica non biologica e biologica.

Trattamenti sistemici non biologici(cambiamento | cambia codice)

  • Il metotrexato è un antagonista della vitamina, l'acido folico. È ancora usato soprattutto nell'artrite psoriasica, poco nella psoriasi esclusivamente cutanea.
  • Un retinoide, come l'acitretina, è un derivato sintetico della vitamina A che può essere prescritto in forme di psoriasi da moderate a gravi. Nelle donne in età fertile questo trattamento è teratogeno, non solo durante l'assunzione del farmaco, ma anche durante i due anni (24 mesi) successivi all'ultima dose. Gli effetti collaterali sono generalmente minori.
  • Poiché la psoriasi è considerata vicino alle malattie autoimmuni, un immunosoppressore come la ciclosporina può talvolta produrre effetti positivi, ma i suoi effetti collaterali sono importanti (principalmente a causa dell'indebolimento del sistema immunitario). L'idrossiurea non viene quasi più utilizzata.
  • il , la Food and Drug Administration (FDA) ha concesso l'apremilast (Portare via) in pazienti con psoriasi a placche da moderata a grave che sono candidati per fototerapia o terapia sistemica