TUTTI I MIGLIOR PRODOTTI PER IL BENESSERE

PRINCETON, N.J.–(BUSINESS WIRE)–Bristol-Myers Squibb Company (NYSE: BMY) today announced Japan’s Ministry of Health, Labor and Welfare (MHLW) has approved Opdivo (nivolumab) for the treatment of patients with unresectable advanced or recurrent esophageal cancer that has progressed following chemotherapy.

This approval is based on the Phase 3 ATTRACTION-3 trial, which evaluated Opdivo versus chemotherapy (docetaxel or paclitaxel) for the treatment of patients with unresectable advanced or recurrent esophageal squamous cell carcinoma (ESCC) refractory or intolerant to combination therapy with fluoropyrimidine and platinum-based drugs. For the primary endpoint of overall survival (OS), Opdivo demonstrated a 23% reduction in the risk of death (Hazard Ratio (HR) 0.77; 95% Confidence Interval (CI): 0.62 to 0.96; p=0.019) and a 2.5-month improvement in median OS (10.9 months (95% CI: 9.2 to 13.3)) compared with chemotherapy (8.4 months (95% CI: 7.2 to 9.9)). The safety profile of Opdivo in this trial was consistent with previously reported studies in solid tumors. The ATTRACTION-3 trial was sponsored by Ono Pharmaceutical Co. Ltd. of Japan, Bristol-Myers Squibb’s development partner for Opdivo.

“Alongside our partner, Ono Pharmaceutical, we are proud to offer Opdivo as an alternative to chemotherapy for patients in Japan with esophageal cancer, regardless of their PD-L1 status,” said Fouad Namouni, M.D., head, Oncology Development, Bristol-Myers Squibb. “This first-ever approval of Opdivo in esophageal cancer exemplifies our commitment to advancing treatment options with the potential to extend survival for patients with difficult-to-treat gastrointestinal cancers.”

About ATTRACTION-3

ATTRACTION-3 (ONO-4538-24/CA209-473; NCT02569242) is a Phase 3, multi-center, randomized, open-label global study, evaluating Opdivo versus chemotherapy (docetaxel or paclitaxel) for patients with esophageal cancer refractory or intolerant to first-line combination therapy with fluoropyrimidine and platinum-based drugs. Patient enrollment occurred predominantly in Asia, with the remainder in the United States and Europe. Patients were treated until disease progression or unacceptable toxicity. The primary endpoint of the trial was OS. Secondary endpoints include investigator-assessed objective response rate, progression-free survival, disease control rate, duration of response and safety.

Patients treated in the Opdivo arm showed 12- and 18-month OS rates of 47% (95% CI: 40 to 54) and 31% (95% CI: 24 to 37), respectively, versus 34% (95% CI: 28 to 41) and 21% (95% CI: 15 to 27) among patients in the chemotherapy arm. Survival benefit with Opdivo was observed regardless of tumor PD-L1 expression levels. An exploratory analysis of patient-reported outcomes showed significant overall improvement in quality of life with Opdivo versus chemotherapy.

Fewer treatment-related adverse events (TRAEs) were reported with Opdivo versus chemotherapy, with a rate of 66% of any grade TRAEs for patients receiving Opdivo compared to 95% for patients receiving chemotherapy. Patients in the Opdivo arm also experienced a lower incidence of Grade 3 or 4 TRAEs compared to those in the chemotherapy arm (18% versus 63%), and the percentage of patients experiencing TRAEs leading to discontinuation was the same in both arms (9%).

Data from the study were featured in a Presidential Symposium during the European Society for Medical Oncology 2019 Annual Congress and simultaneously published in The Lancet Oncology.

About Esophageal Cancer

Esophageal cancer is the seventh most common cancer and the sixth most common cause of death from cancer worldwide. The five-year relative survival rate is 8% or less for patients diagnosed with metastatic disease. Globally, an estimated 572,000 new cases of esophageal cancer are diagnosed each year, nearly 80% of which occur in Asia. In Japan, approximately 20,000 cases are diagnosed and 12,000 deaths are caused by esophageal cancer every year. The two most common types of esophageal cancer are adenocarcinoma and squamous cell carcinoma, the latter accounting for approximately 90% of all esophageal cancer cases diagnosed in Japan. The majority of cases are diagnosed in the advanced setting and impact a patient’s daily life, including their ability to eat and drink.

Bristol-Myers Squibb: Advancing Oncology Research

At Bristol-Myers Squibb, patients are at the center of everything we do. The focus of our research is to increase quality, long-term survival for patients and make cure a possibility. Through a unique multidisciplinary approach powered by translational science, we harness our deep scientific experience in oncology and Immuno-Oncology (I-O) research to identify novel treatments tailored to individual patient needs. Our researchers are developing a diverse, purposefully built pipeline designed to target different immune system pathways and address the complex and specific interactions between the tumor, its microenvironment and the immune system. We source innovation internally, and in collaboration with academia, government, advocacy groups and biotechnology companies, to help make the promise of transformational medicines, like I-O, a reality for patients.

About Opdivo

Opdivo is a programmed death-1 (PD-1) immune checkpoint inhibitor that is designed to uniquely harness the body’s own immune system to help restore anti-tumor immune response. By harnessing the body’s own immune system to fight cancer, Opdivo has become an important treatment option across multiple cancers.

Opdivo’s leading global development program is based on Bristol-Myers Squibb’s scientific expertise in the field of Immuno-Oncology, and includes a broad range of clinical trials across all phases, including Phase 3, in a variety of tumor types. To date, the Opdivo clinical development program has treated more than 35,000 patients. The Opdivo trials have contributed to gaining a deeper understanding of the potential role of biomarkers in patient care, particularly regarding how patients may benefit from Opdivo across the continuum of PD-L1 expression.

In July 2014, Opdivo was the first PD-1 immune checkpoint inhibitor to receive regulatory approval anywhere in the world. Opdivo is currently approved in more than 65 countries, including the United States, the European Union, Japan and China. In October 2015, the Company’s Opdivo and Yervoy combination regimen was the first Immuno-Oncology combination to receive regulatory approval for the treatment of metastatic melanoma and is currently approved in more than 50 countries, including the United States and the European Union.

U.S. FDA-APPROVED INDICATIONS FOR OPDIVO^®

OPDIVO^® (nivolumab) as a single agent is indicated for the treatment of patients with unresectable or metastatic melanoma.

OPDIVO^® (nivolumab), in combination with YERVOY^® (ipilimumab), is indicated for the treatment of patients with unresectable or metastatic melanoma.

OPDIVO^® (nivolumab) is indicated for the treatment of patients with metastatic non-small cell lung cancer (NSCLC) with progression on or after platinum-based chemotherapy. Patients with EGFR or ALK genomic tumor aberrations should have disease progression on FDA-approved therapy for these aberrations prior to receiving OPDIVO.

OPDIVO^® (nivolumab) is indicated for the treatment of patients with metastatic small cell lung cancer (SCLC) with progression after platinum-based chemotherapy and at least one other line of therapy. This indication is approved under accelerated approval based on overall response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials.

OPDIVO^® (nivolumab) is indicated for the treatment of patients with advanced renal cell carcinoma (RCC) who have received prior anti-angiogenic therapy.

OPDIVO^® (nivolumab), in combination with YERVOY^® (ipilimumab), is indicated for the treatment of patients with intermediate or poor risk, previously untreated advanced renal cell carcinoma (RCC).

OPDIVO^® (nivolumab) is indicated for the treatment of adult patients with classical Hodgkin lymphoma (cHL) that has relapsed or progressed after autologous hematopoietic stem cell transplantation (HSCT) and brentuximab vedotin or after 3 or more lines of systemic therapy that includes autologous HSCT. This indication is approved under accelerated approval based on overall response rate. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials.

OPDIVO^® (nivolumab) is indicated for the treatment of patients with recurrent or metastatic squamous cell carcinoma of the head and neck (SCCHN) with disease progression on or after platinum-based therapy.

OPDIVO^® (nivolumab) is indicated for the treatment of patients with locally advanced or metastatic urothelial carcinoma who have disease progression during or following platinum-containing chemotherapy or have disease progression within 12 months of neoadjuvant or adjuvant treatment with platinum-containing chemotherapy. This indication is approved under accelerated approval based on tumor response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials.

OPDIVO^® (nivolumab), as a single agent, is indicated for the treatment of adult and pediatric (12 years and older) patients with microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) metastatic colorectal cancer (CRC) that has progressed following treatment with a fluoropyrimidine, oxaliplatin, and irinotecan. This indication is approved under accelerated approval based on overall response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials.

OPDIVO^® (nivolumab), in combination with YERVOY^® (ipilimumab), is indicated for the treatment of adults and pediatric patients 12 years and older with microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) metastatic colorectal cancer (CRC) that has progressed following treatment with a fluoropyrimidine, oxaliplatin, and irinotecan. This indication is approved under accelerated approval based on overall response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials.

OPDIVO^® (nivolumab) is indicated for the treatment of patients with hepatocellular carcinoma (HCC) who have been previously treated with sorafenib. This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials.

OPDIVO^® (nivolumab) is indicated for the adjuvant treatment of patients with melanoma with involvement of lymph nodes or metastatic disease who have undergone complete resection.

IMPORTANT SAFETY INFORMATION

WARNING: IMMUNE-MEDIATED ADVERSE REACTIONS

YERVOY can result in severe and fatal immune-mediated adverse reactions. These immune-mediated reactions may involve any organ system; however, the most common severe immune-mediated adverse reactions are enterocolitis, hepatitis, dermatitis (including toxic epidermal necrolysis), neuropathy, and endocrinopathy. The majority of these immune-mediated reactions initially manifested during treatment; however, a minority occurred weeks to months after discontinuation of YERVOY.

Assess patients for signs and symptoms of enterocolitis, dermatitis, neuropathy, and endocrinopathy, and evaluate clinical chemistries including liver function tests (LFTs), adrenocorticotropic hormone (ACTH) level, and thyroid function tests, at baseline and before each dose.

Permanently discontinue YERVOY and initiate systemic high-dose corticosteroid therapy for severe immune-mediated reactions.

Immune-Mediated Pneumonitis

OPDIVO can cause immune-mediated pneumonitis. Fatal cases have been reported. Monitor patients for signs with radiographic imaging and for symptoms of pneumonitis. Administer corticosteroids for Grade 2 or more severe pneumonitis. Permanently discontinue for Grade 3 or 4 and withhold until resolution for Grade 2. In patients receiving OPDIVO monotherapy, fatal cases of immune-mediated pneumonitis have occurred. Immune-mediated pneumonitis occurred in 3.1% (61/1994) of patients. In patients receiving OPDIVO 1 mg/kg with YERVOY 3 mg/kg, immune-mediated pneumonitis occurred in 6% (25/407) of patients. In RCC patients receiving OPDIVO 3 mg/kg with YERVOY 1 mg/kg, immune-mediated pneumonitis occurred in 4.4% (24/547) of patients. In MSI-H/dMMR mCRC patients receiving OPDIVO 3 mg/kg with YERVOY 1 mg/kg, immune-mediated pneumonitis occurred in 1.7% (2/119) of patients.

In Checkmate 205 and 039, pneumonitis, including interstitial lung disease, occurred in 6.0% (16/266) of patients receiving OPDIVO. Immune-mediated pneumonitis occurred in 4.9% (13/266) of patients receiving OPDIVO: Grade 3 (n=1) and Grade 2 (n=12).

Immune-Mediated Colitis

OPDIVO can cause immune-mediated colitis. Monitor patients for signs and symptoms of colitis. Administer corticosteroids for Grade 2 (of more than 5 days duration), 3, or 4 colitis. Withhold OPDIVO monotherapy for Grade 2 or 3 and permanently discontinue for Grade 4 or recurrent colitis upon re-initiation of OPDIVO. When administered with YERVOY, withhold OPDIVO and YERVOY for Grade 2 and permanently discontinue for Grade 3 or 4 or recurrent colitis. In patients receiving OPDIVO monotherapy, immune-mediated colitis occurred in 2.9% (58/1994) of patients. In patients receiving OPDIVO 1 mg/kg with YERVOY 3 mg/kg, immune-mediated colitis occurred in 26% (107/407) of patients including three fatal cases. In RCC patients receiving OPDIVO 3 mg/kg with YERVOY 1 mg/kg, immune-mediated colitis occurred in 10% (52/547) of patients. In MSI-H/dMMR mCRC patients receiving OPDIVO 3 mg/kg with YERVOY 1 mg/kg, immune-mediated colitis occurred in 7% (8/119) of patients.

In a separate Phase 3 study of YERVOY 3 mg/kg, severe, life-threatening, or fatal (diarrhea of ≥7 stools above baseline, fever, ileus, peritoneal signs; Grade 3-5) immune-mediated enterocolitis occurred in 34 (7%) patients. Across all YERVOY-treated patients in that study (n=511), 5 (1%) developed intestinal perforation, 4 (0.8%) died as a result of complications, and 26 (5%) were hospitalized for severe enterocolitis.

Immune-Mediated Hepatitis

OPDIVO can cause immune-mediated hepatitis. Monitor patients for abnormal liver tests prior to and periodically during treatment. Administer corticosteroids for Grade 2 or greater transaminase elevations. For patients without HCC, withhold OPDIVO for Grade 2 and permanently discontinue OPDIVO for Grade 3 or 4. For patients with HCC, withhold OPDIVO and administer corticosteroids if AST/ALT is within normal limits at baseline and increases to >3 and up to 5 times the upper limit of normal (ULN), if AST/ALT is >1 and up to 3 times ULN at baseline and increases to >5 and up to 10 times the ULN, and if AST/ALT is >3 and up to 5 times ULN at baseline and increases to >8 and up to 10 times the ULN. Permanently discontinue OPDIVO and administer corticosteroids if AST or ALT increases to >10 times the ULN or total bilirubin increases >3 times the ULN. In patients receiving OPDIVO monotherapy, immune-mediated hepatitis occurred in 1.8% (35/1994) of patients. In patients receiving OPDIVO 1 mg/kg with YERVOY 3 mg/kg, immune-mediated hepatitis occurred in 13% (51/407) of patients. In RCC patients receiving OPDIVO 3 mg/kg with YERVOY 1 mg/kg, immune-mediated hepatitis occurred in 7% (38/547) of patients. In MSI-H/dMMR mCRC patients receiving OPDIVO 3 mg/kg with YERVOY 1 mg/kg, immune-mediated hepatitis occurred in 8% (10/119) of patients.

In Checkmate 040, immune-mediated hepatitis requiring systemic corticosteroids occurred in 5% (8/154) of patients receiving OPDIVO.

In a separate Phase 3 study of YERVOY 3 mg/kg, severe, life-threatening, or fatal hepatotoxicity (AST or ALT elevations >5x the ULN or total bilirubin elevations >3x the ULN; Grade 3-5) occurred in 8 (2%) patients, with fatal hepatic failure in 0.2% and hospitalization in 0.4%.

Immune-Mediated Neuropathies

In a separate Phase 3 study of YERVOY 3 mg/kg, 1 case of fatal Guillain-Barré syndrome and 1 case of severe (Grade 3) peripheral motor neuropathy were reported.

Immune-Mediated Endocrinopathies

OPDIVO can cause immune-mediated hypophysitis, immune-mediated adrenal insufficiency, autoimmune thyroid disorders, and Type 1 diabetes mellitus. Monitor patients for signs and symptoms of hypophysitis, signs and symptoms of adrenal insufficiency, thyroid function prior to and periodically during treatment, and hyperglycemia. Administer hormone replacement as clinically indicated and corticosteroids for Grade 2 or greater hypophysitis. Withhold for Grade 2 or 3 and permanently discontinue for Grade 4 hypophysitis. Administer corticosteroids for Grade 3 or 4 adrenal insufficiency. Withhold for Grade 2 and permanently discontinue for Grade 3 or 4 adrenal insufficiency. Administer hormone-replacement therapy for hypothyroidism. Initiate medical management for control of hyperthyroidism. Withhold OPDIVO for Grade 3 and permanently discontinue for Grade 4 hyperglycemia.

In patients receiving OPDIVO monotherapy, hypophysitis occurred in 0.6% (12/1994) of patients. In patients receiving OPDIVO 1 mg/kg with YERVOY 3 mg/kg, hypophysitis occurred in 9% (36/407) of patients. In RCC patients receiving OPDIVO 3 mg/kg with YERVOY 1 mg/kg, hypophysitis occurred in 4.6% (25/547) of patients. In MSI-H/dMMR mCRC patients receiving OPDIVO 3 mg/kg with YERVOY 1 mg/kg, immune-mediated hypophysitis occurred in 3.4% (4/119) of patients. In patients receiving OPDIVO monotherapy, adrenal insufficiency occurred in 1% (20/1994) of patients. In patients receiving OPDIVO 1 mg/kg with YERVOY 3 mg/kg, adrenal insufficiency occurred in 5% (21/407) of patients. In RCC patients receiving OPDIVO 3 mg/kg with YERVOY 1 mg/kg, adrenal insufficiency occurred in 7% (41/547) of patients. In MSI-H/dMMR mCRC patients receiving OPDIVO 3 mg/kg with YERVOY 1 mg/kg, adrenal insufficiency occurred in 5.9% (7/119) of patients. In patients receiving OPDIVO monotherapy, hypothyroidism or thyroiditis resulting in hypothyroidism occurred in 9% (171/1994) of patients. Hyperthyroidism occurred in 2.7% (54/1994) of patients receiving OPDIVO monotherapy. In patients receiving OPDIVO 1 mg/kg with YERVOY 3 mg/kg, hypothyroidism or thyroiditis resulting in hypothyroidism occurred in 22% (89/407) of patients. Hyperthyroidism occurred in 8% (34/407) of patients receiving this dose of OPDIVO with YERVOY. In RCC patients receiving OPDIVO 3 mg/kg with YERVOY 1 mg/kg, hypothyroidism or thyroiditis resulting in hypothyroidism occurred in 22% (119/547) of patients. Hyperthyroidism occurred in 12% (66/547) of patients receiving this dose of OPDIVO with YERVOY. In MSI-H/dMMR mCRC patients receiving OPDIVO 3 mg/kg with YERVOY 1 mg/kg, hypothyroidism or thyroiditis resulting in hypothyroidism occurred in 15% (18/119) of patients. Hyperthyroidism occurred in 12% (14/119) of patients. In patients receiving OPDIVO monotherapy, diabetes occurred in 0.9% (17/1994) of patients. In patients receiving OPDIVO 1 mg/kg with YERVOY 3 mg/kg, diabetes occurred in 1.5% (6/407) of patients. In RCC patients receiving OPDIVO 3 mg/kg with YERVOY 1 mg/kg, diabetes occurred in 2.7% (15/547) of patients.

In a separate Phase 3 study of YERVOY 3 mg/kg, severe to life-threatening immune-mediated endocrinopathies (requiring hospitalization, urgent medical intervention, or interfering with activities of daily living; Grade 3-4) occurred in 9 (1.8%) patients. All 9 patients had hypopituitarism, and some had additional concomitant endocrinopathies such as adrenal insufficiency, hypogonadism, and hypothyroidism. Six of the 9 patients were hospitalized for severe endocrinopathies.

Immune-Mediated Nephritis and Renal Dysfunction

OPDIVO can cause immune-mediated nephritis. Monitor patients for elevated serum creatinine prior to and periodically during treatment. Administer corticosteroids for Grades 2-4 increased serum creatinine. Withhold OPDIVO for Grade 2 or 3 and permanently discontinue for Grade 4 increased serum creatinine. In patients receiving OPDIVO monotherapy, immune-mediated nephritis and renal dysfunction occurred in 1.2% (23/1994) of patients. In patients receiving OPDIVO 1 mg/kg with YERVOY 3 mg/kg, immune-mediated nephritis and renal dysfunction occurred in 2.2% (9/407) of patients. In RCC patients receiving OPDIVO 3 mg/kg with YERVOY 1 mg/kg, immune-mediated nephritis and renal dysfunction occurred in 4.6% (25/547) of patients. In MSI-H/dMMR mCRC patients receiving OPDIVO 3 mg/kg with YERVOY 1 mg/kg, immune-mediated nephritis and renal dysfunction occurred in 1.7% (2/119) of patients.

Immune-Mediated Skin Adverse Reactions and Dermatitis

OPDIVO can cause immune-mediated rash, including Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN), some cases with fatal outcome. Administer corticosteroids for Grade 3 or 4 rash. Withhold for Grade 3 and permanently discontinue for Grade 4 rash. For symptoms or signs of SJS or TEN, withhold OPDIVO and refer the patient for specialized care for assessment and treatment; if confirmed, permanently discontinue. In patients receiving OPDIVO monotherapy, immune-mediated rash occurred in 9% (171/1994) of patients. In patients receiving OPDIVO 1 mg/kg with YERVOY 3 mg/kg, immune-mediated rash occurred in 22.6% (92/407) of patients. In RCC patients receiving OPDIVO 3 mg/kg with YERVOY 1 mg/kg, immune-mediated rash occurred in 16% (90/547) of patients. In MSI-H/dMMR mCRC patients receiving OPDIVO 3 mg/kg with YERVOY 1 mg/kg, immune-mediated rash occurred in 14% (17/119) of patients.

In a separate Phase 3 study of YERVOY 3 mg/kg, severe, life-threatening, or fatal immune-mediated dermatitis (eg, Stevens-Johnson syndrome, toxic epidermal necrolysis, or rash complicated by full thickness dermal ulceration, or necrotic, bullous, or hemorrhagic manifestations; Grade 3-5) occurred in 13 (2.5%) patients. 1 (0.2%) patient died as a result of toxic epidermal necrolysis. 1 additional patient required hospitalization for severe dermatitis.

Immune-Mediated Encephalitis

OPDIVO can cause immune-mediated encephalitis. Evaluation of patients with neurologic symptoms may include, but not be limited to, consultation with a neurologist, brain MRI, and lumbar puncture. Withhold OPDIVO in patients with new-onset moderate to severe neurologic signs or symptoms and evaluate to rule out other causes. If other etiologies are ruled out, administer corticosteroids and permanently discontinue OPDIVO for immune-mediated encephalitis. In patients receiving OPDIVO monotherapy, encephalitis occurred in 0.2% (3/1994) of patients. Fatal limbic encephalitis occurred in one patient after 7.2 months of exposure despite discontinuation of OPDIVO and administration of corticosteroids. Encephalitis occurred in one patient receiving OPDIVO 1 mg/kg with YERVOY 3 mg/kg (0.2%) after 1.7 months of exposure. Encephalitis occurred in one RCC patient receiving OPDIVO 3 mg/kg with YERVOY 1 mg/kg (0.2%) after approximately 4 months of exposure. Encephalitis occurred in one MSI-H/dMMR mCRC patient (0.8%) receiving OPDIVO 3 mg/kg with YERVOY 1 mg/kg after 15 days of exposure.

Other Immune-Mediated Adverse Reactions

Based on the severity of the adverse reaction, permanently discontinue or withhold OPDIVO, administer high-dose corticosteroids, and, if appropriate, initiate hormone-replacement therapy. Across clinical trials of OPDIVO monotherapy or in combination with YERVOY, the following clinically significant immune-mediated adverse reactions, some with fatal outcome, occurred in <1.0% of patients receiving OPDIVO: myocarditis, rhabdomyolysis, myositis, uveitis, iritis, pancreatitis, facial and abducens nerve paresis, demyelination, polymyalgia rheumatica, autoimmune neuropathy, Guillain-Barré syndrome, hypopituitarism, systemic inflammatory response syndrome, gastritis, duodenitis, sarcoidosis, histiocytic necrotizing lymphadenitis (Kikuchi lymphadenitis), motor dysfunction, vasculitis, aplastic anemia, pericarditis, and myasthenic syndrome.

If uveitis occurs in combination with other immune-mediated adverse reactions, consider a Vogt-Koyanagi-Harada-like syndrome, which has been observed in patients receiving OPDIVO and may require treatment with systemic steroids to reduce the risk of permanent vision loss.

Infusion Reactions

OPDIVO can cause severe infusion reactions, which have been reported in <1.0% of patients in clinical trials. Discontinue OPDIVO in patients with Grade 3 or 4 infusion reactions. Interrupt or slow the rate of infusion in patients with Grade 1 or 2. In patients receiving OPDIVO monotherapy as a 60-minute infusion, infusion-related reactions occurred in 6.4% (127/1994) of patients. In a separate study in which patients received OPDIVO monotherapy as a 60-minute infusion or a 30-minute infusion, infusion-related reactions occurred in 2.2% (8/368) and 2.7% (10/369) of patients, respectively. Additionally, 0.5% (2/368) and 1.4% (5/369) of patients, respectively, experienced adverse reactions within 48 hours of infusion that led to dose delay, permanent discontinuation or withholding of OPDIVO. In patients receiving OPDIVO 1 mg/kg with YERVOY 3 mg/kg every 3 weeks, infusion-related reactions occurred in 2.5% (10/407) of patients. In RCC patients receiving OPDIVO 3 mg/kg with YERVOY 1 mg/kg, infusion-related reactions occurred in 5.1% (28/547) of patients. In MSI-H/dMMR mCRC patients receiving OPDIVO 3 mg/kg with YERVOY 1 mg/kg, infusion-related reactions occurred in 4.2% (5/119) of patients.

Complications of Allogeneic Hematopoietic Stem Cell Transplantation

Fatal and other serious complications can occur in patients who receive allogeneic hematopoietic stem cell transplantation (HSCT) before or after being treated with a PD-1 receptor blocking antibody. Transplant-related complications include hyperacute graft-versus-host-disease (GVHD), acute GVHD, chronic GVHD, hepatic veno-occlusive disease (VOD) after reduced intensity conditioning, and steroid-requiring febrile syndrome (without an identified infectious cause). These complications may occur despite intervening therapy between PD-1 blockade and allogeneic HSCT.

Follow patients closely for evidence of transplant-related complications and intervene promptly. Consider the benefit versus risks of treatment with a PD-1 receptor blocking antibody prior to or after an allogeneic HSCT.

Embryo-Fetal Toxicity

Based on their mechanisms of action, OPDIVO and YERVOY can cause fetal harm when administered to a pregnant woman. Advise pregnant women of the potential risk to a fetus. Advise females of reproductive potential to use effective contraception during treatment with an OPDIVO- or YERVOY- containing regimen and for at least 5 months after the last dose of OPDIVO.

Increased Mortality in Patients with Multiple Myeloma when OPDIVO is Added to a Thalidomide Analogue and Dexamethasone

In clinical trials in patients with multiple myeloma, the addition of OPDIVO to a thalidomide analogue plus dexamethasone resulted in increased mortality. Treatment of patients with multiple myeloma with a PD-1 or PD-L1 blocking antibody in combination with a thalidomide analogue plus dexamethasone is not recommended outside of controlled clinical trials.

Lactation

It is not known whether OPDIVO or YERVOY is present in human milk. Because many drugs, including antibodies, are excreted in human milk and because of the potential for serious adverse reactions in nursing infants from an OPDIVO-containing regimen, advise women to discontinue breastfeeding during treatment. Advise women to discontinue breastfeeding during treatment with YERVOY and for 3 months following the final dose.

Serious Adverse Reactions

In Checkmate 037, serious adverse reactions occurred in 41% of patients receiving OPDIVO (n=268). Grade 3 and 4 adverse reactions occurred in 42% of patients receiving OPDIVO. The most frequent Grade 3 and 4 adverse drug reactions reported in 2% to <5% of patients receiving OPDIVO were abdominal pain, hyponatremia, increased aspartate aminotransferase, and increased lipase. In Checkmate 066, serious adverse reactions occurred in 36% of patients receiving OPDIVO (n=206). Grade 3 and 4 adverse reactions occurred in 41% of patients receiving OPDIVO. The most frequent Grade 3 and 4 adverse reactions reported in ≥2% of patients receiving OPDIVO were gamma-glutamyltransferase increase (3.9%) and diarrhea (3.4%). In Checkmate 067, serious adverse reactions (74% and 44%), adverse reactions leading to permanent discontinuation (47% and 18%) or to dosing delays (58% and 36%), and Grade 3 or 4 adverse reactions (72% and 51%) all occurred more frequently in the OPDIVO plus YERVOY arm (n=313) relative to the OPDIVO arm (n=313). The most frequent (≥10%) serious adverse reactions in the OPDIVO plus YERVOY arm and the OPDIVO arm, respectively, were diarrhea (13% and 2.2%), colitis (10% and 1.9%), and pyrexia (10% and 1.0%). In Checkmate 017 and 057, serious adverse reactions occurred in 46% of patients receiving OPDIVO (n=418). The most frequent serious adverse reactions reported in ≥2% of patients receiving OPDIVO were pneumonia, pulmonary embolism, dyspnea, pyrexia, pleural effusion, pneumonitis, and respiratory failure. In Checkmate 032, serious adverse reactions occurred in 45% of patients receiving OPDIVO (n=245). The most frequent serious adverse reactions reported in at least 2% of patients receiving OPDIVO were pneumonia, dyspnea, pneumonitis, pleural effusions, and dehydration. In Checkmate 025, serious adverse reactions occurred in 47% of patients receiving OPDIVO (n=406). The most frequent serious adverse reactions reported in ≥2% of patients were acute kidney injury, pleural effusion, pneumonia, diarrhea, and hypercalcemia. In Checkmate 214, serious adverse reactions occurred in 59% of patients receiving OPDIVO plus YERVOY and in 43% of patients receiving sunitinib. The most frequent serious adverse reactions reported in ≥2% of patients were diarrhea, pyrexia, pneumonia, pneumonitis, hypophysitis, acute kidney injury, dyspnea, adrenal insufficiency, and colitis; in patients treated with sunitinib, they were pneumonia, pleural effusion, and dyspnea. In Checkmate 205 and 039, adverse reactions leading to discontinuation occurred in 7% and dose delays due to adverse reactions occurred in 34% of patients (n=266). Serious adverse reactions occurred in 26% of patients. The most frequent serious adverse reactions reported in ≥1% of patients were pneumonia, infusion-related reaction, pyrexia, colitis or diarrhea, pleural effusion, pneumonitis, and rash. Eleven patients died from causes other than disease progression: 3 from adverse reactions within 30 days of the last OPDIVO dose, 2 from infection 8 to 9 months after completing OPDIVO, and 6 from complications of allogeneic HSCT. In Checkmate 141, serious adverse reactions occurred in 49% of patients receiving OPDIVO (n=236). The most frequent serious adverse reactions reported in ≥2% of patients receiving OPDIVO were pneumonia, dyspnea, respiratory failure, respiratory tract infection, and sepsis. In Checkmate 275, serious adverse reactions occurred in 54% of patients receiving OPDIVO (n=270). The most frequent serious adverse reactions reported in ≥2% of patients receiving OPDIVO were urinary tract infection, sepsis, diarrhea, small intestine obstruction, and general physical health deterioration. In Checkmate 142 in MSI-H/dMMR mCRC patients receiving OPDIVO with YERVOY, serious adverse reactions occurred in 47% of patients. The most frequent serious adverse reactions reported in ≥2% of patients were colitis/diarrhea, hepatic events, abdominal pain, acute kidney injury, pyrexia, and dehydration. In Checkmate 040, serious adverse reactions occurred in 49% of patients (n=154). The most frequent serious adverse reactions reported in ≥2% of patients were pyrexia, ascites, back pain, general physical health deterioration, abdominal pain, and pneumonia. In Checkmate 238, Grade 3 or 4 adverse reactions occurred in 25% of OPDIVO-treated patients (n=452). The most frequent Grade 3 and 4 adverse reactions reported in ≥2% of OPDIVO-treated patients were diarrhea and increased lipase and amylase. Serious adverse reactions occurred in 18% of OPDIVO-treated patients.

Common Adverse Reactions

In Checkmate 037, the most common adverse reaction (≥20%) reported with OPDIVO (n=268) was rash (21%). In Checkmate 066, the most common adverse reactions (≥20%) reported with OPDIVO (n=206) vs dacarbazine (n=205) were fatigue (49% vs 39%), musculoskeletal pain (32% vs 25%), rash (28% vs 12%), and pruritus (23% vs 12%). In Checkmate 067, the most common (≥20%) adverse reactions in the OPDIVO plus YERVOY arm (n=313) were fatigue (62%), diarrhea (54%), rash (53%), nausea (44%), pyrexia (40%), pruritus (39%), musculoskeletal pain (32%), vomiting (31%), decreased appetite (29%), cough (27%), headache (26%), dyspnea (24%), upper respiratory tract infection (23%), arthralgia (21%), and increased transaminases (25%). In Checkmate 067, the most common (≥20%) adverse reactions in the OPDIVO arm (n=313) were fatigue (59%), rash (40%), musculoskeletal pain (42%), diarrhea (36%), nausea (30%), cough (28%), pruritus (27%), upper respiratory tract infection (22%), decreased appetite (22%), headache (22%), constipation (21%), arthralgia (21%), and vomiting (20%). In Checkmate 017 and 057, the most common adverse reactions (≥20%) in patients receiving OPDIVO (n=418) were fatigue, musculoskeletal pain, cough, dyspnea, and decreased appetite. In Checkmate 032, the most common adverse reactions (≥20%) in patients receiving OPDIVO (n=245) were fatigue (45%), decreased appetite (27%), musculoskeletal pain (25%), dyspnea (22%), nausea (22%), diarrhea (21%), constipation (20%), and cough (20%). In Checkmate 025, the most common adverse reactions (≥20%) reported in patients receiving OPDIVO (n=406) vs everolimus (n=397) were fatigue (56% vs 57%), cough (34% vs 38%), nausea (28% vs 29%), rash (28% vs 36%), dyspnea (27% vs 31%), diarrhea (25% vs 32%), constipation (23% vs 18%), decreased appetite (23% vs 30%), back pain (21% vs 16%), and arthralgia (20% vs 14%). In Checkmate 214, the most common adverse reactions (≥20%) reported in patients treated with OPDIVO plus YERVOY (n=547) vs sunitinib (n=535) were fatigue (58% vs 69%), rash (39% vs 25%), diarrhea (38% vs 58%), musculoskeletal pain (37% vs 40%), pruritus (33% vs 11%), nausea (30% vs 43%), cough (28% vs 25%), pyrexia (25% vs 17%), arthralgia (23% vs 16%), decreased appetite (21% vs 29%), dyspnea (20% vs 21%), and vomiting (20% vs 28%). In Checkmate 205 and 039, the most common adverse reactions (≥20%) reported in patients receiving OPDIVO (n=266) were upper respiratory tract infection (44%), fatigue (39%), cough (36%), diarrhea (33%), pyrexia (29%), musculoskeletal pain (26%), rash (24%), nausea (20%) and pruritus (20%). In Checkmate 141, the most common adverse reactions (≥10%) in patients receiving OPDIVO (n=236) were cough and dyspnea at a higher incidence than investigator’s choice. In Checkmate 275, the most common adverse reactions (≥20%) reported in patients receiving OPDIVO (n=270) were fatigue (46%), musculoskeletal pain (30%), nausea (22%), and decreased appetite (22%). In Checkmate 142 in MSI-H/dMMR mCRC patients receiving OPDIVO as a single agent, the most common adverse reactions (≥20%) were fatigue (54%), diarrhea (43%), abdominal pain (34%), nausea (34%), vomiting (28%), musculoskeletal pain (28%), cough (26%), pyrexia (24%), rash (23%), constipation (20%), and upper respiratory tract infection (20%). In Checkmate 142 in MSI-H/dMMR mCRC patients receiving OPDIVO with YERVOY, the most common adverse reactions (≥20%) were fatigue (49%), diarrhea (45%), pyrexia (36%), musculoskeletal pain (36%), abdominal pain (30%), pruritus (28%), nausea (26%), rash (25%), decreased appetite (20%), and vomiting (20%). In Checkmate 040, the most common adverse reactions (≥20%) in patients receiving OPDIVO (n=154) were fatigue (38%), musculoskeletal pain (36%), abdominal pain (34%), pruritus (27%), diarrhea (27%), rash (26%), cough (23%), and decreased appetite (22%). In Checkmate 238, the most common adverse reactions (≥20%) reported in OPDIVO-treated patients (n=452) vs ipilimumab-treated patients (n=453) were fatigue (57% vs 55%), diarrhea (37% vs 55%), rash (35% vs 47%), musculoskeletal pain (32% vs 27%), pruritus (28% vs 37%), headache (23% vs 31%), nausea (23% vs 28%), upper respiratory infection (22% vs 15%), and abdominal pain (21% vs 23%). The most common immune-mediated adverse reactions were rash (16%), diarrhea/colitis (6%), and hepatitis (3%).

In a separate Phase 3 study of YERVOY 3 mg/kg, the most common adverse reactions (≥5%) in patients who received YERVOY at 3 mg/kg were fatigue (41%), diarrhea (32%), pruritus (31%), rash (29%), and colitis (8%).

Recommended Dose Modifications

Interrupt or slow the rate of infusion in patients with mild or moderate infusion reactions. Discontinue in patients with severe or life-threatening infusion reactions.

Endocrine: Withhold YERVOY for symptomatic endocrinopathy. Resume YERVOY in patients with complete or partial resolution of adverse reactions (Grade 0-1) and who are receiving <7.5 mg prednisone or equivalent per day. Permanently discontinue YERVOY for symptomatic reactions lasting 6 weeks or longer or an inability to reduce corticosteroid dose to 7.5 mg prednisone or equivalent per day.

Ophthalmologic: Permanently discontinue YERVOY for Grade 2-4 reactions not improving to Grade 1 within 2 weeks while receiving topical therapy or requiring systemic treatment.

All Other Organ Systems: Withhold YERVOY for Grade 2 adverse reactions. Resume YERVOY in patients with complete or partial resolution of adverse reactions (Grade 0-1) and who are receiving <7.5 mg prednisone or equivalent per day. Permanently discontinue YERVOY for Grade 2 reactions lasting 6 weeks or longer, an inability to reduce corticosteroid dose to 7.5 mg prednisone or equivalent per day, and Grade 3 or 4 adverse reactions.

Immune-Mediated Enterocolitis

Immune-mediated enterocolitis, including fatal cases, can occur with YERVOY. Monitor patients for signs and symptoms of enterocolitis (such as diarrhea, abdominal pain, mucus or blood in stool, with or without fever) and of bowel perforation (such as peritoneal signs and ileus). In symptomatic patients, rule out infectious etiologies and consider endoscopic evaluation for persistent or severe symptoms. Withhold YERVOY for moderate enterocolitis; administer anti-diarrheal treatment and, if persistent for >1 week, initiate systemic corticosteroids (0.5 mg/kg/day prednisone or equivalent). Permanently discontinue YERVOY in patients with severe enterocolitis and initiate systemic corticosteroids (1-2 mg/kg/day of prednisone or equivalent). Upon improvement to ≤Grade 1, initiate corticosteroid taper and continue over at least 1 month. In clinical trials, rapid corticosteroid tapering resulted in recurrence or worsening symptoms of enterocolitis in some patients. Consider adding anti-TNF or other immunosuppressant agents for management of immune-mediated enterocolitis unresponsive to systemic corticosteroids within 3-5 days or recurring after symptom improvement, if other causes are excluded. In patients receiving YERVOY 3 mg/kg in MDX010-20, severe, life-threatening, or fatal (diarrhea of ≥7 stools above baseline, fever, ileus, peritoneal signs; Grade 3-5) immune-mediated enterocolitis occurred in 34 YERVOY-treated patients (7%) and moderate (diarrhea with up to 6 stools above baseline, abdominal pain, mucus or blood in stool; Grade 2) enterocolitis occurred in 28 YERVOY-treated patients (5%). Across all YERVOY-treated patients (n=511), 5 (1%) developed intestinal perforation, 4 (0.8%) died as a result of complications, and 26 (5%) were hospitalized for severe enterocolitis. Infliximab was administered to 5 (8%) of the 62 patients with moderate, severe, or life-threatening immune-mediated enterocolitis following inadequate response to corticosteroids. In patients receiving YERVOY 10 mg/kg in CA184-029, Grade 3-5 immune-mediated enterocolitis occurred in 76 patients (16%) and Grade 2 enterocolitis occurred in 68 patients (14%). Seven (1.5%) developed intestinal perforation and 3 patients (0.6%) died as a result of complications.

Cytomegalovirus (CMV) infection/reactivation has been reported in patients with corticosteroid-refractory immune-mediated colitis. In cases of corticosteroid-refractory colitis, consider repeating infectious workup to exclude alternative etiologies. Addition of an alternative immunosuppressive agent to the corticosteroid therapy, or replacement of the corticosteroid therapy, should be considered in corticosteroid-refractory immune-mediated colitis if other causes are excluded.

Immune-Mediated Hepatitis

Immune-mediated hepatitis, including fatal cases, can occur with YERVOY. Monitor LFTs (hepatic transaminase and bilirubin levels) and assess patients for signs and symptoms of hepatotoxicity before each dose of YERVOY. In patients with hepatotoxicity, rule out infectious or malignant causes and increase frequency of LFT monitoring until resolution. Withhold YERVOY in patients with Grade 2 hepatotoxicity. Permanently discontinue YERVOY in patients with Grade 3-4 hepatotoxicity and administer systemic corticosteroids (1-2 mg/kg/day of prednisone or equivalent). When LFTs show sustained improvement or return to baseline, initiate corticosteroid tapering and continue over 1 month. Across the clinical development program for YERVOY, mycophenolate treatment has been administered in patients with persistent severe hepatitis despite high-dose corticosteroids. In patients receiving YERVOY 3 mg/kg in MDX010-20, severe, life-threatening, or fatal hepatotoxicity (AST or ALT elevations >5× the ULN or total bilirubin elevations >3× the ULN; Grade 3-5) occurred in 8 YERVOY-treated patients (2%), with fatal hepatic failure in 0.2% and hospitalization in 0.4%. An additional 13 patients (2.5%) experienced moderate hepatotoxicity manifested by LFT abnormalities (AST or ALT elevations >2.5× but ≤5× the ULN or total bilirubin elevation >1.5× but ≤3× the ULN; Grade 2). In a dose-finding trial, Grade 3 increases in transaminases with or without concomitant increases in total bilirubin occurred in 6 of 10 patients who received concurrent YERVOY (3 mg/kg) and vemurafenib (960 mg BID or 720 mg BID). In patients receiving YERVOY 10 mg/kg in CA184-029, Grade 3-4 immune-mediated hepatitis occurred in 51 patients (11%) and moderate Grade 2 immune-mediated hepatitis occurred in 22 patients (5%). Liver biopsy performed in 6 patients with Grade 3-4 hepatitis showed evidence of toxic or autoimmune hepatitis.

Immune-Mediated Dermatitis

Immune-mediated dermatitis, including fatal cases, can occur with YERVOY. Monitor patients for signs and symptoms of dermatitis such as rash and pruritus. Unless an alternate etiology has been identified, signs or symptoms of dermatitis should be considered immune-mediated. Treat mild to moderate dermatitis (e.g., localized rash and pruritus) symptomatically; administer topical or systemic corticosteroids if there is no improvement within 1 week. Withhold YERVOY in patients with moderate to severe signs and symptoms. Permanently discontinue YERVOY in patients with severe, life-threatening, or fatal immune-mediated dermatitis (Grade 3-5). Administer systemic corticosteroids (1-2 mg/kg/day of prednisone or equivalent). When dermatitis is controlled, corticosteroid tapering should occur over a period of at least 1 month. In patients receiving YERVOY 3 mg/kg in MDX010-20, severe, life-threatening, or fatal immune-mediated dermatitis (e.g., Stevens-Johnson syndrome, toxic epidermal necrolysis, or rash complicated by full thickness dermal ulceration, or necrotic, bullous, or hemorrhagic manifestations; Grade 3-5) occurred in 13 YERVOY-treated patients (2.5%); 1 patient (0.2%) died as a result of toxic epidermal necrolysis and 1 additional patient required hospitalization for severe dermatitis. There were 63 patients (12%) with moderate (Grade 2) dermatitis. In patients receiving YERVOY 10 mg/kg in CA184-029, Grade 3-4 immune-mediated dermatitis occurred in 19 patients (4%). There were 99 patients (21%) with moderate Grade 2 dermatitis.

Immune-Mediated Neuropathies

Immune-mediated neuropathies, including fatal cases, can occur with YERVOY. Monitor for symptoms of motor or sensory neuropathy such as unilateral or bilateral weakness, sensory alterations, or paresthesia. Withhold YERVOY in patients with moderate neuropathy (not interfering with daily activities). Permanently discontinue YERVOY in patients with severe neuropathy (interfering with daily activities), such as Guillain-Barré-like syndromes. Institute medical intervention as appropriate for management for severe neuropathy. Consider initiation of systemic corticosteroids (1-2 mg/kg/day of prednisone or equivalent) for severe neuropathies. In patients receiving YERVOY 3 mg/kg in MDX010-20, 1 case of fatal Guillain-Barré syndrome and 1 case of severe (Grade 3) peripheral motor neuropathy were reported. Across the clinical development program of YERVOY, myasthenia gravis and additional cases of Guillain-Barré syndrome have been reported. In patients receiving YERVOY 10 mg/kg in CA184-029, Grade 3-5 immune-mediated neuropathy occurred in 8 patients (2%); the sole fatality was due to complications of Guillain-Barré syndrome. Moderate Grade 2 immune-mediated neuropathy occurred in 1 patient (0.2%).

Immune-Mediated Endocrinopathies

Immune-mediated endocrinopathies, including life-threatening cases, can occur with YERVOY. Monitor patients for clinical signs and symptoms of hypophysitis, adrenal insufficiency (including adrenal crisis), and hyper- or hypothyroidism. Patients may present with fatigue, headache, mental status changes, abdominal pain, unusual bowel habits, and hypotension, or nonspecific symptoms which may resemble other causes such as brain metastasis or underlying disease. Unless an alternate etiology has been identified, signs or symptoms should be considered immune-mediated. Monitor clinical chemistries, adrenocorticotropic hormone (ACTH) level, and thyroid function tests at the start of treatment, before each dose, and as clinically indicated based on symptoms. In a limited number of patients, hypophysitis was diagnosed by imaging studies through enlargement of the pituitary gland. Withhold YERVOY in symptomatic patients and consider referral to an endocrinologist. Initiate systemic corticosteroids (1-2 mg/kg/day of prednisone or equivalent) and initiate appropriate hormone replacement therapy. In patients receiving YERVOY 3 mg/kg in MDX010-20, severe to life-threatening immune-mediated endocrinopathies (requiring hospitalization, urgent medical intervention, or interfering with activities of daily living; Grade 3-4) occurred in 9 YERVOY-treated patients (1.8%). All 9 patients had hypopituitarism, and some had additional concomitant endocrinopathies such as adrenal insufficiency, hypogonadism, and hypothyroidism. Six of the 9 patients were hospitalized for severe endocrinopathies. Moderate endocrinopathy (requiring hormone replacement or medical intervention; Grade 2) occurred in 12 patients (2.3%) and consisted of hypothyroidism, adrenal insufficiency, hypopituitarism, and 1 case each of hyperthyroidism and Cushing’s syndrome. The median time to onset of moderate to severe immune-mediated endocrinopathy was 2.5 months and ranged up to 4.4 months after the initiation of YERVOY. In patients receiving YERVOY 10 mg/kg in CA184-029, Grade 3-4 immune-mediated endocrinopathies occurred in 39 patients (8%) and Grade 2 immune-mediated endocrinopathies occurred in 93 patients (20%). Of the 39 patients with Grade 3-4 immune-mediated endocrinopathies, 35 patients had hypopituitarism (associated with 1 or more secondary endocrinopathies, e.g., adrenal insufficiency, hypogonadism, and hypothyroidism), 3 patients had hyperthyroidism, and 1 had primary hypothyroidism. The median time to onset of Grade 3-4 immune-mediated endocrinopathy was 2.2 months (range: 2 days-8 months). Twenty-seven (69.2%) of the 39 patients were hospitalized for immune-mediated endocrinopathies. Of the 93 patients with Grade 2 immune-mediated endocrinopathy, 74 had primary hypopituitarism (associated with 1 or more secondary endocrinopathy, e.g., adrenal insufficiency, hypogonadism, and hypothyroidism), 9 had primary hypothyroidism, 3 had hyperthyroidism, 3 had thyroiditis with hypo- or hyperthyroidism, 2 had hypogonadism, 1 had both hyperthyroidism and hypopituitarism, and 1 subject developed Graves’ ophthalmopathy. The median time to onset of Grade 2 immune-mediated endocrinopathy was 2.1 months (range: 9 days-19.3 months).

Other Immune-Mediated Adverse Reactions

Permanently discontinue YERVOY for clinically significant or severe immune-mediated adverse reactions. Initiate systemic corticosteroids (1-2 mg/kg/day of prednisone or equivalent) for severe immune-mediated adverse reactions. Monitor patients for signs or symptoms of ocular toxicity, which may include blurred vision and reduced visual acuity. Immune-mediated ocular toxicity may be associated with retinal detachment or permanent vision loss. Administer corticosteroid eye drops for uveitis, iritis, or episcleritis. Permanently discontinue YERVOY for immune-mediated ocular disease unresponsive to local immunosuppressive therapy. If uveitis occurs in combination with other immune-mediated adverse reactions, consider a Vogt-Koyanagi-Harada-like syndrome, which has been observed in patients receiving YERVOY and may require treatment with systemic steroids to reduce the risk of permanent vision loss. Fatal or serious graft-versus-host disease (GVHD) can occur in patients who receive a CTLA-4 receptor blocking antibody either before or after allogeneic hematopoietic stem cell transplantation (HSCT). Follow patients closely for evidence of GVHD and intervene promptly. Consider the benefit versus risks of treatment with a CTLA-4 receptor blocking antibody after allogeneic HSCT. In MDX010-20, the following clinically significant immune-mediated adverse reactions were seen in <1% of YERVOY-treated patients: cytopenias, nephritis, pneumonitis, meningitis, pericarditis, uveitis, and iritis. In CA184-029, the following clinically significant immune-mediated adverse reactions were seen in <1% of YERVOY-treated patients unless specified: cytopenias, eosinophilia (2.1%), pancreatitis (1.3%), meningitis, pneumonitis, sarcoidosis, pericarditis, uveitis, and fatal myocarditis. Across 21 dose-ranging trials administering YERVOY at doses of 0.1 to 20 mg/kg (n=2478), the following likely immune-mediated adverse reactions were also reported with <1% incidence unless specified: angiopathy, temporal arteritis, vasculitis, polymyalgia rheumatica, conjunctivitis, blepharitis, episcleritis, scleritis, iritis, leukocytoclastic vasculitis, erythema multiforme, psoriasis, arthritis, autoimmune thyroiditis, neurosensory hypoacusis, autoimmune central neuropathy (encephalitis), myositis, polymyositis, ocular myositis, cytopenias (2.5%), and nephritis.

Embryo-Fetal Toxicity

Based on its mechanism of action, YERVOY can cause fetal harm when administered to a pregnant woman. The effects of YERVOY are likely to be greater during the second and third trimesters of pregnancy. Advise pregnant women of the potential risk to a fetus. Advise females of reproductive potential to use effective contraception during treatment with YERVOY and for 3 months after the last dose.

Lactation

It is not known whether YERVOY is secreted in human milk. Advise women not to breastfeed during treatment with YERVOY and for 3 months after the last dose.

Common Adverse Reactions

The most common adverse reactions (≥5%) in patients who received YERVOY at 3 mg/kg were fatigue (41%), diarrhea (32%), pruritus (31%), rash (29%), and colitis (8%). The most common adverse reactions (≥5%) in patients who received YERVOY at 10 mg/kg were rash (50%), diarrhea (49%), fatigue (46%), pruritus (45%), headache (33%), weight loss (32%), nausea (25%), pyrexia (18%), colitis (16%), decreased appetite (14%), vomiting (13%), and insomnia (10%).

Please see U.S. Full Prescribing Information for OPDIVO and YERVOY, including Boxed WARNING regarding immune-mediated adverse reactions for YERVOY.

Checkmate Trials and Patient Populations

Checkmate 037–previously treated metastatic melanoma; Checkmate 066–previously untreated metastatic melanoma; Checkmate 067–previously untreated metastatic melanoma, as a single agent or in combination with YERVOY; Checkmate 017–second-line treatment of metastatic squamous non-small cell lung cancer; Checkmate 057–second-line treatment of metastatic non-squamous non-small cell lung cancer; Checkmate 032–small cell lung cancer; Checkmate 025–previously treated renal cell carcinoma; Checkmate 214–previously untreated renal cell carcinoma, in combination with YERVOY; Checkmate 205/039–classical Hodgkin lymphoma; Checkmate 141–recurrent or metastatic squamous cell carcinoma of the head and neck; Checkmate 275–urothelial carcinoma; Checkmate 142–MSI-H or dMMR metastatic colorectal cancer, as a single agent or in combination with YERVOY; Checkmate 040–hepatocellular carcinoma; Checkmate 238–adjuvant treatment of melanoma.

About the Bristol-Myers Squibb and Ono Pharmaceutical Collaboration

In 2011, through a collaboration agreement with Ono Pharmaceutical Co., Bristol-Myers Squibb expanded its territorial rights to develop and commercialize Opdivo globally, except in Japan, South Korea and Taiwan, where Ono had retained all rights to the compound at the time. On July 23, 2014, Ono and Bristol-Myers Squibb further expanded the companies’ strategic collaboration agreement to jointly develop and commercialize multiple immunotherapies – as single agents and combination regimens – for patients with cancer in Japan, South Korea and Taiwan.

About Bristol-Myers Squibb

Bristol-Myers Squibb is a global biopharmaceutical company whose mission is to discover, develop and deliver innovative medicines that help patients prevail over serious diseases. For more information about Bristol-Myers Squibb, visit us at BMS.com or follow us on LinkedIn, Twitter, YouTube, Facebook and Instagram.

Celgene and Juno Therapeutics are wholly owned subsidiaries of Bristol-Myers Squibb Company. In certain countries outside the U.S., due to local laws, Celgene and Juno Therapeutics are referred to as, Celgene, a Bristol-Myers Squibb company and Juno Therapeutics, a Bristol-Myers Squibb company.

Cautionary Statement Regarding Forward-Looking Statements

This press release contains “forward-looking statements” within the meaning of the Private Securities Litigation Reform Act of 1995 regarding, among other things, the research, development and commercialization of pharmaceutical products. All statements that are not statements of historical facts are, or may be deemed to be, forward-looking statements. Such forward-looking statements are based on historical performance and current expectations and projections about our future financial results, goals, plans and objectives and involve inherent risks, assumptions and uncertainties, including internal or external factors that could delay, divert or change any of them in the next several years, that are difficult to predict, may be beyond our control and could cause our future financial results, goals, plans and objectives to differ materially from those expressed in, or implied by, the statements. These risks, assumptions, uncertainties and other factors include, among others, Opdivo may not receive regulatory approval from the U.S. Food and Drug Administration or other regulatory authorities for the additional indication described in this release and whether such product candidate for such additional indication described in this release will be commercially successful. No forward-looking statement can be guaranteed. Forward-looking statements in this press release should be evaluated together with the many risks and uncertainties that affect Bristol-Myers Squibb’s business and market, particularly those identified in the cautionary statement and risk factors discussion in Bristol-Myers Squibb’s Annual Report on Form 10-K for the year ended December 31, 2018, as updated by our subsequent Quarterly Reports on Form 10-Q, Current Reports on Form 8-K and other filings with the Securities and Exchange Commission. The forward-looking statements included in this document are made only as of the date of this document and except as otherwise required by applicable law, Bristol-Myers Squibb undertakes no obligation to publicly update or revise any forward-looking statement, whether as a result of new information, future events, changed circumstances or otherwise.

BRUXELLES, 20 febbraio 2020 / PRNewswire / – 7:00 (CET) – informazioni regolamentate – “data-reagente =” 12 “>BRUXELLES, 20 febbraio 2020 / PRNewswire / – 7:00 (CET) – informazioni regolamentate –

• I ricavi hanno raggiunto € 4,9 miliardi (+ 6%, + 7% CER⁽¹⁾) le vendite nette sono aumentate a 4,7 miliardi di euro (+ 6%)
• Redditività sottostante (rEBITDA⁽²⁾) è stato di 1,4 miliardi di euro (+ 2%, + 11% CER) o del 29,1% delle entrate
• Aggiornamento R&S: bimekizumab con tre risultati positivi di Fase 3 nella psoriasi e iniziato un nuovo programma di Fase 3 nell'idradenite suppurativa; Cimzia^® con approvazioni in Cina e Giappone
• Previsioni finanziarie per il 2020: le entrate dovrebbero raggiungere € 5,05 – 5,15 miliardi,
  REBITDA⁽²⁾ 28 – 29% delle entrate, core EPS⁽³⁾ di € 4,80 – 5,20 previsto
• Nuova guida alle vendite di punta per Cimzia^® 2,0 miliardi di euro entro il 2024 e per Vimpat^® 1,5 miliardi di euro entro il 2022
• Nuova composizione del comitato esecutivo di UCB nel 2020

Jean-Christophe Tellier, CEO UCB. “In base alla nostra promettente pipeline in fase avanzata e all'acquisizione di Ra Pharma in sospeso, potremmo potenzialmente lanciare fino a 7 prodotti entro il 2025 per creare valore per il paziente per popolazioni specifiche ora e in futuro. Inoltre, ci concentriamo su quattro aree di sostenibilità che sono fondamentali al nostro successo a lungo termine e al nostro contributo alla società. “” data -eagid = “21”> “Il 2019 è stato un anno di forte crescita e crescita. Pertanto, abbiamo aggiornato la guida alle vendite di punta per Cimzia® e Vimpat® e continuiamo ad accelerare i nostri investimenti in futuri fattori di crescita “, ha affermato Jean-Christophe Tellier, CEO UCB. “In base alla nostra promettente pipeline in fase avanzata e all'acquisizione di Ra Pharma in sospeso, potremmo potenzialmente lanciare fino a 7 prodotti entro il 2025 per creare valore per il paziente per popolazioni specifiche ora e in futuro. Inoltre, ci concentriamo su quattro aree di sostenibilità che sono fondamentali al nostro successo a lungo termine e al nostro contributo alla società “.

Il Consiglio di amministrazione di UCB propone un dividendo di € 1,24 per azione (lordo), + 2%.

Gennaio 2020, è iniziato lo studio di fase 3 su pazienti con trombocitopenia immunitaria (ITP), i primi risultati attesi sono attesi in H 2 2022. “data-reagid =” 29 “> In Gennaio 2020, è iniziato lo studio di fase 3 su pazienti con trombocitopenia immunitaria (ITP), i primi risultati attesi sono attesi in H 2 2022.

Maggio 2019. “data-reactionid =” 32 “> A dicembre è stato lanciato UCB Nayzilam^® (midazolam) Spray nasale ^CIV, il primo e unico trattamento di salvataggio nasale per i gruppi epilettici negli Stati Uniti Nayzilam^® spray nasale è stato approvato negli Stati Uniti a Maggio 2019.

Cina.
A dicembre, Cimzia^® è stato approvato per il trattamento della psoriasi e dell'artrite psoriasica in Giappone. “data-reactionid =” 33 “>Immunologia
Nel mese di luglio, Cimzia^® (certolizumab pegol) è stato approvato in associazione con metotrexato per il trattamento dell'artrite reumatoide attiva da moderata a grave in pazienti adulti in Cina.
A dicembre, Cimzia^® è stato approvato per il trattamento della psoriasi e dell'artrite psoriasica in Giappone.

Giappone, gli Stati Uniti., Corea del Sud, Canada e Australia nonché nell'UE. “data -eagid =” 41 “>Evenity^® (romosozumab) è ora approvato in Giappone, gli Stati Uniti., Corea del Sud, Canada e Australia così come nell'UE.

In ottobre, a seguito della procedura di riesame, il comitato per i medicinali per uso umano (CHMP) dell'Agenzia europea per i medicinali (EMA) ha adottato un parere positivo raccomandando l'autorizzazione all'immissione in commercio.

La storia continua

Europa, Le vendite nette di Keppra® sono state influenzate da un adeguamento locale degli sconti una tantum nella prima metà del 2019 “data-reazioni” = “53”>Keppra^® (Levetiracetam) per l'epilessia, ha riportato un fatturato netto di 770 milioni di euro, che riflette sia il marchio forte e affidabile che la maturità del prodotto. Negli Stati Uniti le vendite nette sono state influenzate dalla concorrenza generica. Nel Europa, Le vendite nette di Keppra® sono state influenzate da un adeguamento locale degli sconti una tantum nella prima metà del 2019

Europa sono stati quasi compensati dalla buona crescita dei mercati internazionali. “data -eagid =” 55 “>Neupro^® (Rotigotina), la patch per il morbo di Parkinson, ha mostrato una leggera riduzione delle vendite nette a 319 milioni di euro. Riduzioni minori negli Stati Uniti, dovute all'ambiente di mercato generico – e Europa sono stati quasi compensati da una buona crescita nei mercati internazionali.

Germania e il supplemento di ferro Niferex^® nel primo trimestre del 2019, e prima che le 'coperture designate riclassificate nelle vendite nette' fossero cresciute del + 13% (+ 9% CER). Questa crescita è stata trainata dalla continua forte performance positiva dei prodotti core di UCB.
Le entrate e le commissioni delle royalties sono diminuite a € 78 milioni da € 92 milioni. Le altre entrate sono aumentate a € 155 milioni dopo € 128 milioni. “Data-reazioni =” 57 “> Nel 2019, entrate e vendite nette aumentato del 6% (+ 7% CER) a 4 913 milioni di euro e rispettivamente a 4 680 milioni di euro (+ 6%; + 7% CER). Le vendite nette prima delle “coperture designate riclassificate in vendite nette” sono aumentate dell'11% (+ 7% CER) a 4 784 milioni di euro. Aggiustato per cessioni nel 2018, principalmente “Innere Medizin” /Germania e il supplemento di ferro Niferex^® nel primo trimestre del 2019, e prima che le 'coperture designate riclassificate nelle vendite nette' fossero cresciute del + 13% (+ 9% CER). Questa crescita è stata trainata dalla continua forte performance positiva dei prodotti core di UCB.
Le entrate e le commissioni delle royalties sono diminuite a € 78 milioni da € 92 milioni. Gli altri ricavi sono aumentati a € 155 milioni dopo € 128 milioni.

Europa e nella spondiloartrite assiale non radiografica attiva (nr-axSpA) negli Stati Uniti, nonché i preparativi per il lancio di Evenity^® nel Europa, Spese di ricerca e sviluppo superiori del 10% di € & nbsp; 1 & nbsp; 272 & nbsp; milioni – trainate da maggiori investimenti in R & amp; D e risultanti in un rapporto di R & amp; D del 26% nel 2019 dopo il 25% nel 2018 e dell'8% in più in generale e amministrativo spese per € 195 milioni, principalmente in relazione al nuovo modello organizzativo implementato nel 2019. Gli altri ricavi operativi sono stati € 48 milioni dopo spese di € 24 milioni nel 2018. I ricavi sono composti da contributi agli investimenti, utili su cessioni , liberazione di accantonamenti e entrate derivanti dalla collaborazione con Amgen in relazione a Evenity^®. Ciò ha comportato un rapporto spese operative (in relazione ai ricavi) del 51% dopo il 50% nel 2018. “data-reazioni” = “59”>Spese operative ha raggiunto 2 527 milioni di euro (+ 9%; + 6% CER) riflettendo un aumento del 15% delle spese di marketing e vendita di 1 108 milioni di euro – guidato dal lancio di Cimzia^® nella psoriasi negli Stati Uniti e Europa e nella spondiloartrite assiale non radiografica attiva (nr-axSpA) negli Stati Uniti, nonché i preparativi per il lancio di Evenity^® nel Europa, Il 10% in più di spese di ricerca e sviluppo di 1 272 milioni di euro – trainati da maggiori investimenti in ricerca e sviluppo e risultante in un rapporto di ricerca e sviluppo del 26% nel 2019 dopo il 25% nel 2018 e 8% in più di spese generali e amministrative di 195 milioni di euro, principalmente connessione con il nuovo modello organizzativo implementato nel 2019. Gli altri ricavi operativi sono stati pari a 48 milioni di euro dopo spese di 24 milioni di euro nel 2018. I proventi sono composti da contributi agli investimenti, utili da cessione, liberazione di accantonamenti e proventi derivanti dalla collaborazione con Amgen in relazione con uniformità^®. Ciò ha comportato un rapporto spese operative (in relazione ai ricavi) del 51% dopo il 50% nel 2018.

Sei anni consecutivi di crescita hanno sottolineato nel tempo le solide prestazioni di UCB. UCB è pronta ad accelerare ulteriormente e ad espandersi per soddisfare le sue ambizioni di valore per il paziente, potenzialmente lanciando sei o sette nuovi prodotti entro il 2025.

Jean-Christophe Tellier, CEO di UCB “data -eagid =” 70 “>” Per supportare le nostre ambizioni, abbiamo evoluto la nostra organizzazione e i nostri modi di lavorare per assicurarci di diventare più agili e collaborare più trasversalmente all'interno della nostra organizzazione. Riteniamo che questa organizzazione evoluta aumenterà la nostra chiarezza operativa ed efficienza e ci preparerà per lanci incentrati sul valore per il paziente “, ha affermato Jean-Christophe Tellier, CEO di UCB

Questa evoluzione si riflette nella nuova composizione del Comitato Esecutivo UCB che è diventato più piccolo, con ruoli più trasversali tra le imprese e le regioni e con una maggiore attenzione alle aree di attività principali dell'azienda.

1o febbraio 2020 la nuova composizione del Comitato Esecutivo di UCB è la seguente: “data -eagid =” 72 “> Da 1o febbraio 2020 la nuova composizione del Comitato esecutivo di UCB è la seguente:

• Jean-Christophe Tellier, Amministratore delegato
• Emmanuel Caeymaex, Vicepresidente esecutivo per le soluzioni immunologiche e capo degli Stati Uniti
• Jean-Luc Fleurial, Vicepresidente esecutivo e direttore delle risorse umane
• Iris Löw-Friedrich, Vicepresidente esecutivo e Chief Medical Officer
• Kirsten Lund-Jurgensen, Vicepresidente esecutivo, Soluzioni di approvvigionamento e tecnologia
• Dhaval Patel, Vicepresidente esecutivo e Direttore scientifico
• Bill Silbey, Vicepresidente esecutivo e consigliere generale
• Detlef Thielgen, Vicepresidente esecutivo, Direttore finanziario e Sviluppo aziendale
• Charl van Zyl, Executive Vice President Neurology Solutions e Head of EU / International

Alexander Moscho, Pascale Richetta, Bharat Tewarie e Jeff Wren hanno lasciato il Comitato Esecutivo e UCB è molto grato per i loro contributi passati. Bill Silbey e Kirsten Lund-Jurgensen è entrato a far parte del Comitato esecutivo nel 2019.
Inoltre, UCB ha annunciato in Luglio 2019 che il Chief Financial Officer dell'azienda, Detlef Thielgen, uscirà da UCB nel primo semestre 2020. È in corso la ricerca di un successore. “data -eagid =” 83 “>Alexander Moscho, Pascale Richetta, Bharat Tewarie e Jeff Wren hanno lasciato il Comitato Esecutivo e UCB è molto grato per i loro contributi passati. Bill Silbey e Kirsten Lund-Jurgensen è entrato a far parte del Comitato esecutivo nel 2019.
Inoltre, UCB ha annunciato in Luglio 2019 che il Chief Financial Officer dell'azienda, Detlef Thielgen, uscirà da UCB nel primo semestre 2020. È in corso la ricerca di un successore.

https://www.ucb.com/investors/UCB-Governance#book-CMP_B_55790“data -eagid =” 84 “> Ulteriori informazioni sul Comitato esecutivo di UCB sono disponibili sul sito Web di UCB: https://www.ucb.com/investors/UCB-Governance#book-CMP_B_55790

http://www.ucb.com/investors/Download-center& nbsp; “data -eagid =” 85 “> Trova i rapporti finanziari FY sul sito Web UCB: http://www.ucb.com/investors/Download-center

Oggi UCB ospiterà una teleconferenza / webcast video alle 08.00 (EST) / 13.00 (GMT) / 14.00 (CET).

https://www.ucb.com/investors/UCB-financials/Full-year-financial-results“data -eagid =” 87 “> I dettagli sono disponibili su https://www.ucb.com/investors/UCB-financials/Full-year-financial-results

Bruxelles, Belgio (www.ucb.com) è una società biofarmaceutica globale focalizzata sulla scoperta e lo sviluppo di farmaci e soluzioni innovativi per trasformare la vita delle persone che vivono con gravi malattie del sistema immunitario o del sistema nervoso centrale. Con oltre 7 persone in circa 40 paesi, la società ha generato ricavi per € 4,9 miliardi nel 2019. UCB è quotata su Euronext Bruxelles (simbolo: UCB). Seguiteci su Twitter: @UCB_news “data -eagid =” 88 “>Informazioni su UCB
UCB, Bruxelles, Belgio (www.ucb.com) è una società biofarmaceutica globale focalizzata sulla scoperta e lo sviluppo di farmaci e soluzioni innovativi per trasformare la vita delle persone che vivono con gravi malattie del sistema immunitario o del sistema nervoso centrale. Con oltre 7 600 persone in circa 40 paesi, la società ha generato ricavi per € 4,9 miliardi nel 2019. UCB è quotata su Euronext Bruxelles (simbolo: UCB). Seguiteci su Twitter: @UCB_news

Given these uncertainties, you should not place undue reliance on any of such forward-looking statements. There can be no guarantee that the investigational or approved products described in this press release will be submitted or approved for sale or for any additional indications or labelling in any market, or at any particular time, nor can there be any guarantee that such products will be or will continue to be commercially successful in the future.

UCB is providing this information, including forward-looking statements, only as of the date of this press release and expressly disclaims any duty to update any information contained in this press release, either to confirm the actual results or to report or reflect any change in its forward-looking statements with regard thereto or any change in events, conditions or circumstances on which any such statement is based, unless such statement is required pursuant to applicable laws and regulations.

Additionally, information contained in this document shall not constitute an offer to sell or the solicitation of an offer to buy any securities, nor shall there be any offer, solicitation or sale of securities in any jurisdiction in which such offer, solicitation or sale would be unlawful prior to the registration or qualification under the securities laws of such jurisdiction.

(1) CER = constant exchange rates

(3) Core EPS = core earnings per share

(4) Due to rounding, some financial data may not add up in the tables.

(5) Due to rounding, some financial data may not add up in the tables.

(6) rEBITDA = recurring Earnings Before Interest, Taxes, Depreciation and Amortization charges

http://www.prnewswire.com/news-releases/ucb-full-year-report-2019-301007945.html” data-reactid=”111″>View original content:http://www.prnewswire.com/news-releases/ucb-full-year-report-2019-301007945.html

SOURCE UCB

https://www.fortunebusinessinsights.com/enquiry/speak-to-analyst/in-vitro-fertilization-ivf-market-102189
” data-reactid=”43″>
Have Any Query? Ask Our Experts: https://www.fortunebusinessinsights.com/enquiry/speak-to-analyst/in-vitro-fertilization-ivf-market-102189

TOC Continued….!
” data-reactid=”51″>TOC Continued….!

https://www.fortunebusinessinsights.com/enquiry/customization/in-vitro-fertilization-ivf-market-102189
” data-reactid=”52″>
Request for Customization: https://www.fortunebusinessinsights.com/enquiry/customization/in-vitro-fertilization-ivf-market-102189

In-vitro Diagnostics (IVD) Market Size, Share & Industry Analysis, By Product Type (Instruments, Reagents & Consumables), By Technique (Immunodiagnostics, Clinical Chemistry, Molecular Diagnostics, Point of Care, Hematology and Others), By Application (Infectious Diseases, Cardiology, Oncology, Gastroenterology, Others), By End User (Clinical Laboratories, Hospitals, Physicians Offices, Others) and Regional Forecast, 2019 – 2026″ data-reactid=”54″>In-vitro Diagnostics (IVD) Market Size, Share & Industry Analysis, By Product Type (Instruments, Reagents & Consumables), By Technique (Immunodiagnostics, Clinical Chemistry, Molecular Diagnostics, Point of Care, Hematology and Others), By Application (Infectious Diseases, Cardiology, Oncology, Gastroenterology, Others), By End User (Clinical Laboratories, Hospitals, Physicians Offices, Others) and Regional Forecast, 2019 – 2026

Assisted Reproductive Technology (ART) Market Size, Share & Industry Analysis, By Technique (In-Vitro Fertilization (IVF), Artificial Insemination (AI-IUI), Frozen Embryo Transfer (FET), and Others), By Procedure (Fresh Donor, Fresh Non-donor, Frozen Donor, and Frozen Non-donor), By End User (Fertility Clinics, and Hospitals) and Regional Forecast, 2019-2026″ data-reactid=”55″>Assisted Reproductive Technology (ART) Market Size, Share & Industry Analysis, By Technique (In-Vitro Fertilization (IVF), Artificial Insemination (AI-IUI), Frozen Embryo Transfer (FET), and Others), By Procedure (Fresh Donor, Fresh Non-donor, Frozen Donor, and Frozen Non-donor), By End User (Fertility Clinics, and Hospitals) and Regional Forecast, 2019-2026

Biomarkers Market Size, Share & Industry Analysis, By Indication (Oncology, Cardiology, Neurology, and Others), By End User (Pharmaceutical & Biotechnology Companies, Diagnostics & Research Laboratories, Hospitals & Specialty Clinics, and Others), and Regional Forecast, 2019-2026″ data-reactid=”56″>Biomarkers Market Size, Share & Industry Analysis, By Indication (Oncology, Cardiology, Neurology, and Others), By End User (Pharmaceutical & Biotechnology Companies, Diagnostics & Research Laboratories, Hospitals & Specialty Clinics, and Others), and Regional Forecast, 2019-2026

Neuroendoscopy Devices Market Size, Share & Industry Analysis, By Product Type (Rigid Neuroendoscopes, Flexible Neuroendoscopes), By Application Type (Transnasal Neuroendoscopy, Intraventricular Neuroendoscopy, Transcranial Neuroendoscopy), By End User (Hospitals, Specialty Clinics, Others) and Regional Forecast, 2019-2026″ data-reactid=”57″>Neuroendoscopy Devices Market Size, Share & Industry Analysis, By Product Type (Rigid Neuroendoscopes, Flexible Neuroendoscopes), By Application Type (Transnasal Neuroendoscopy, Intraventricular Neuroendoscopy, Transcranial Neuroendoscopy), By End User (Hospitals, Specialty Clinics, Others) and Regional Forecast, 2019-2026

Next-Generation Sequencing (NGS) Market Size, Share and Industry Analysis By Type (Products, Instruments & Software, Consumables, Services), By Application (Diagnostics, Research), By End User (Research Institutes, Healthcare Facilities & Diagnostic Centres, Pharmaceutical & Biotechnological Companies, Contract Research Organization) & Regional Forecast, 2019 – 2026

Regenerative Medicine Market Size, Share and Industry Analysis By Product (Cell Therapy, Gene Therapy, Tissue Engineering, Platelet Rich Plasma), By Application (Orthopaedics, Wound Care, Oncology), By Distribution Channel (Hospitals, Clinics) & Regional Forecast, 2019 – 2026″ data-reactid=”58″>Next-Generation Sequencing (NGS) Market Size, Share and Industry Analysis By Type (Products, Instruments & Software, Consumables, Services), By Application (Diagnostics, Research), By End User (Research Institutes, Healthcare Facilities & Diagnostic Centres, Pharmaceutical & Biotechnological Companies, Contract Research Organization) & Regional Forecast, 2019 – 2026

Regenerative Medicine Market Size, Share and Industry Analysis By Product (Cell Therapy, Gene Therapy, Tissue Engineering, Platelet Rich Plasma), By Application (Orthopaedics, Wound Care, Oncology), By Distribution Channel (Hospitals, Clinics) & Regional Forecast, 2019 – 2026

Genomics Market Size, Share and Industry Analysis By Type (Products, Services), Technology (Polymerase Chain Reaction, Next-generation Sequencing, Microarray, Sanger Sequencing), Application (Diagnostics, Research), End-User (Research Institutes, Healthcare Facilities & Diagnostic Centers, Pharmaceutical & Biotechnological Companies, Contract Research Organization (CROs)) & Regional Forecast, 2019 – 2026″ data-reactid=”59″>Genomics Market Size, Share and Industry Analysis By Type (Products, Services), Technology (Polymerase Chain Reaction, Next-generation Sequencing, Microarray, Sanger Sequencing), Application (Diagnostics, Research), End-User (Research Institutes, Healthcare Facilities & Diagnostic Centers, Pharmaceutical & Biotechnological Companies, Contract Research Organization (CROs)) & Regional Forecast, 2019 – 2026

Contract Research Organization (CRO) Services Market Size, Share and Industry Analysis By Service Type (Discovery, Pre-Clinical, Clinical, Laboratory Services), By Application (Oncology, Cardiology, Infectious Disease, Metabolic Disorders, Others), By End User (Pharmaceutical & Biotechnological Companies, Medical Device Companies, Academic & Research Institutes, Others), and Regional Forecast 2019-2026″ data-reactid=”60″>Contract Research Organization (CRO) Services Market Size, Share and Industry Analysis By Service Type (Discovery, Pre-Clinical, Clinical, Laboratory Services), By Application (Oncology, Cardiology, Infectious Disease, Metabolic Disorders, Others), By End User (Pharmaceutical & Biotechnological Companies, Medical Device Companies, Academic & Research Institutes, Others), and Regional Forecast 2019-2026

Immunology Market Size, Share and Industry Analysis By Drug Class (Monoclonal antibody (mAb), Fusion Proteins, Immunosuppressant, Polyclonal antibody (pAb), Others), By Disease Indication (Rheumatoid Arthritis, Psoriatic Arthritis, Plaque Psoriasis, Ankylosing Spondylitis, Inflammatory Bowel Disease, Prophylaxis of Organ Rejection, Others), By Distribution Channel, and Regional Forecast 2019-2026″ data-reactid=”61″>Immunology Market Size, Share and Industry Analysis By Drug Class (Monoclonal antibody (mAb), Fusion Proteins, Immunosuppressant, Polyclonal antibody (pAb), Others), By Disease Indication (Rheumatoid Arthritis, Psoriatic Arthritis, Plaque Psoriasis, Ankylosing Spondylitis, Inflammatory Bowel Disease, Prophylaxis of Organ Rejection, Others), By Distribution Channel, and Regional Forecast 2019-2026

Immunodiagnostics Market Size, Share and Industry Analysis By Product Instruments, Reagents & Consumables), By Application (Oncology & Endocrinology, Hepatitis & Retrovirus, Cardiac Markers, Infectious Diseases), By End user (Clinical Laboratories, Hospitals, Physician’s Offices), By End-user(Hospitals, Dental Clinics, Academic & Research Institutes) and Regional Forecast, 2019 – 2026″ data-reactid=”62″>Immunodiagnostics Market Size, Share and Industry Analysis By Product Instruments, Reagents & Consumables), By Application (Oncology & Endocrinology, Hepatitis & Retrovirus, Cardiac Markers, Infectious Diseases), By End user (Clinical Laboratories, Hospitals, Physician’s Offices), By End-user(Hospitals, Dental Clinics, Academic & Research Institutes) and Regional Forecast, 2019 – 2026

Orthobiologics Market Size, Share and Industry Analysis by Product Type (Viscosupplements, Bone Growth Stimulators, Demineralized Bone Matrix, Synthetic Bone Substitutes, Stem Cells, Allografts), By Application (Spinal Fusion, Maxillofacial & Dental, Soft Tissue Repair, Reconstructive & Fracture Surgery), By End User (Hospitals, Ambulatory Surgical Centers, Speciality Clinics), and Regional Forecast 2019-2026″ data-reactid=”63″>Orthobiologics Market Size, Share and Industry Analysis by Product Type (Viscosupplements, Bone Growth Stimulators, Demineralized Bone Matrix, Synthetic Bone Substitutes, Stem Cells, Allografts), By Application (Spinal Fusion, Maxillofacial & Dental, Soft Tissue Repair, Reconstructive & Fracture Surgery), By End User (Hospitals, Ambulatory Surgical Centers, Speciality Clinics), and Regional Forecast 2019-2026

Fortune Business Insights™ offers expert corporate analysis and accurate data, helping organizations of all sizes make timely decisions. We tailor innovative solutions for our clients, assisting them to address challenges distinct to their businesses. Our goal is to empower our clients with holistic market intelligence, giving a granular overview of the market they are operating in.

Our reports contain a unique mix of tangible insights and qualitative analysis to help companies achieve sustainable growth. Our team of experienced analysts and consultants use industry-leading research tools and techniques to compile comprehensive market studies, interspersed with relevant data.

At Fortune Business Insights™ we aim at highlighting the most lucrative growth opportunities for our clients. We, therefore, offer recommendations, making it easier for them to navigate through technological and market-related changes. Our consulting services are designed to help organizations identify hidden opportunities and understand prevailing competitive challenges.

Fortune Business Insights™
LinkedIn | Twitter | Blogs
” data-reactid=”68″>Contact Us:
Fortune Business Insights™ Pvt. Ltd.
308, Supreme Headquarters,
Survey No. 36, Baner,
Pune-Bangalore Highway,
Pune – 411045, Maharashtra, India.
Phone:
US :+1 424 253 0390
UK : +44 2071 939123
APAC : +91 744 740 1245
Email: sales@fortunebusinessinsights.com
Fortune Business Insights™
LinkedIn | Twitter | Blogs

https://www.fortunebusinessinsights.com/press-release/in-vitro-fertilization-ivf-market-9606
” data-reactid=”69″>Press Release: https://www.fortunebusinessinsights.com/press-release/in-vitro-fertilization-ivf-market-9606

Pune, 20 febbraio 2020 (GLOBE NEWSWIRE) – Il globale Mercato della fecondazione in vitro (FIV) si prevede che le dimensioni raggiungeranno i 36,39 miliardi di USD entro il 2026, con un CAGR del 10,1% entro il 2026. Ciò è attribuibile ai crescenti casi di infertilità tra le persone in tutto il mondo. Questo è più comune nei maschi che nelle femmine. Il valore di mercato è stato di 16,89 miliardi di USD nel 2018. La fecondazione in vitro è un processo di fecondazione in cui lo sperma e le uova vengono recuperati come campione e combinati manualmente nei laboratori. Vari studi dimostrano che quasi mezzo milione di bambini sono nati da questo processo o da altri processi riproduttivi di aiuto. Tali fattori sono responsabili della crescita del mercato della fecondazione in vitro.

Rapporto più recente di Fortune Business Insights ™, intitolato, “Dimensioni del mercato della fecondazione in vitro (IVF), analisi delle quote e del settore, per tipo (IVF convenzionale e IVF con ICSI), per procedura (non donatore fresco, non donatore congelato, donatore fresco e donatore congelato), per fine Utente (ospedali e cliniche della fertilità) e previsioni regionali, 2019-2026 ” fornisce una panoramica a 360 gradi del mercato e dei suoi parametri. Questi includono fattori di crescita, restrizioni, sfide e opportunità. Il rapporto fornisce anche una segmentazione dettagliata del mercato con cifre di mercato come base e previsioni e anche i tassi di crescita annuali composti (CAGR). Oltre a ciò, il rapporto fornisce spunti interessanti sul mercato, sugli sviluppi chiave del settore e sulle altre tendenze del mercato della fecondazione in vitro. Il rapporto è disponibile per la vendita sul sito Web dell'azienda.

Per ulteriori informazioni nell'analisi di questo rapporto, visitare: https://www.fortunebusinessinsights.com/in-vitro-fertilization-ivf-market-102189

Adozione e pratica dello stile di vita sedentario per aggiungere slancio alla crescita del mercato

Al giorno d'oggi, le persone sono più propense agli obiettivi di carriera piuttosto che alla pianificazione familiare, e quindi spesso tendono a optare per le gravidanze tardive. Il numero crescente di tali casi è un fattore trainante del mercato dei fertilizzanti in vitro, come menzionato in precedenza, poiché i casi complicati vengono spesso risolti optando per il trattamento della fecondazione in vitro. Ciò è più comune in nazioni come Regno Unito, Giappone e Stati Uniti. Inoltre, si prevede che l'aumento del numero di infertilità maschile aumenti l'adozione del trattamento per fecondazione in vitro e quindi acceleri la dimensione del mercato della fecondazione in vitro nei prossimi anni. Oltre a ciò, le politiche di rimborso sostenute dal governo e i programmi di sensibilizzazione stanno aiutando la crescita complessiva del mercato della fecondazione in vitro della regione.

Gli analisti di Fortune Business Insights ™ hanno affermato che “le spese e i rischi elevati legati al processo di fecondazione in vitro (IVF) e all'iniezione intracitoplasmatica di spermatozoi (ICSI) possono causare ostacoli al reddito complessivo del mercato della fecondazione in vitro”. Tuttavia, fattori come l'aumento dei casi di obesità tra le persone, l'infertilità tra gli uomini, la pratica dello stile di vita sedentario e altri probabilmente creeranno opportunità di crescita redditizia del mercato della fecondazione in vitro nei prossimi anni.

L'Europa domina il mercato con il numero massimo di casi di trattamento registrati

L'Europa detiene una quota dominante sul mercato della fecondazione in vitro con un fatturato di 7,57 miliardi di USD generato nell'anno 2018. Ciò è attribuibile all'aumento della prevalenza dell'infertilità e alla crescente popolarità del trattamento della fecondazione in vitro nella regione. Dall'altro lato, il mercato del Nord America assisterà a una crescita costante a causa degli alti costi associati al trattamento ICSI e IVF. Secondo i dati FertilityIQ, 2017, negli Stati Uniti, la spesa media di un paziente sottoposto a un singolo ciclo di fecondazione in vitro è di 22.000 USD. Pertanto, i pazienti negli Stati Uniti viaggiano in altri paesi per il trattamento della fecondazione in vitro citando costi inferiori.

Richiedi una copia di prova del rapporto di ricerca: https://www.fortunebusinessinsights.com/enquiry/request-sample-pdf/in-vitro-fertilization-ivf-market-102189

Le aziende stanno investendo nella costruzione di nuovi centri di fertilità per la generazione di entrate

Boston IVF, Pelargos IVF e Monash IVF stanno attualmente dominando il mercato. I produttori del mercato della fecondazione in vitro stanno sviluppando nuovi centri con un trattamento efficiente e di alta qualità in località remote per accelerare la propria generazione di entrate e lasciare il segno nella concorrenza sul mercato. Ciò alla fine accelererà la dimensione complessiva del mercato della fecondazione in vitro.

Significativi sviluppi del settore nel mercato della fecondazione in vitro:

Maggio 2019 – Gli scienziati di Monash IVF hanno sviluppato un nuovo test di screening dell'embrione per ridurre il rischio di aborto spontaneo al momento del trattamento della fecondazione in vitro.

Luglio 2019 – L'apertura di un nuovo centro IVF a servizio completo presso l'ufficio Westshore di Tampa, in Florida, è stata annunciata da Shady Grove Fertility. L'obiettivo principale dietro l'apertura di questo centro è quello di offrire opzioni di trattamento della fertilità accessibili e di alta qualità alla popolazione regionale.

Elenco delle principali società che operano nel mercato della fecondazione in vitro (FIV) includono:

• Monash IVF
• Fertilità Ovation
• Centro IVF Bloom
• Fertilità di Shady Grove
• Centro IVF di Bangkok
• Boston IVF
• Pelargos IVF
• RSMC
• Clinica Group Ambroise Paré
• Altri fornitori di servizi

Hai qualche domanda? Chiedi ai nostri esperti: https://www.fortunebusinessinsights.com/enquiry/speak-to-analyst/in-vitro-fertilization-ivf-market-102189

Tabella dei contenuti dettagliata:

• introduzione
  • Ambito di ricerca
  • Segmentazione del mercato
  • Metodologia di ricerca
  • Definizioni e presupposti
• Sintesi
• Dinamica del mercato
  • Driver di mercato
  • Vincoli di mercato
  • Opportunità di mercato
• Informazioni chiave
  • Prevalenza di infertilità, per paese / regione chiave, 2018
  • Numero di procedure IVF, per Paese / regioni chiave, 2018
  • Numero di cliniche di fertilità registrate, per paesi chiave, 2018
  • Scenario di rimborso, per Paese / regione chiave
  • Principali sviluppi del settore, partenariati, fusioni e acquisizioni
• Analisi di mercato, approfondimenti e previsioni del mercato della fecondazione in vitro globale (IVF), 2015-2026
  • Risultati chiave / Riepilogo
  • Analisi di mercato, approfondimenti e previsioni – per tipo
    • FIV convenzionale
    • FIV con ICSI
  • Analisi di mercato, approfondimenti e previsioni – Per procedura
    • Non donatore fresco
    • Non donatore congelato
    • Donatore fresco
    • Donatore congelato
  • Analisi di mercato, approfondimenti e previsioni – Per utente finale
    • ospedali
    • Cliniche di fertilità
  • Analisi di mercato, approfondimenti e previsioni – Per regione
    • Nord America
    • Europa
    • Asia Pacifico
    • America latina
    • Medio Oriente e Africa

TOC Continua ….

Richiesta di personalizzazione: https://www.fortunebusinessinsights.com/enquiry/customization/in-vitro-fertilization-ivf-market-102189

Dai un'occhiata ai rapporti correlati:

Mercato della diagnostica in vitro (IVD) Dimensioni, condivisione e analisi del settore, per tipo di prodotto (strumenti, reagenti e materiali di consumo), per tecnica (immunodiagnostica, chimica clinica, diagnostica molecolare, punto di cura, ematologia e altri), per applicazione (malattie infettive, cardiologia, oncologia, gastroenterologia, Altri), per utente finale (laboratori clinici, ospedali, uffici medici, altri) e previsioni regionali, 2019-2026

Mercato della tecnologia di riproduzione assistita (ART) Analisi delle dimensioni, della quota e del settore, per tecnica (fecondazione in vitro (IVF), fecondazione artificiale (AI-IUI), trasferimento di embrioni congelati (FET) e altri), per procedura (donatore fresco, non donatore fresco, donatore congelato e non donatori congelati), per utente finale (cliniche per la fertilità e ospedali) e previsioni regionali, 2019-2026

Mercato dei biomarcatori Analisi delle dimensioni, della quota e del settore, per indicazione (oncologia, cardiologia, neurologia e altri), per utente finale (aziende farmaceutiche e biotecnologiche, laboratori di diagnostica e ricerca, ospedali e cliniche specializzate e altri) e previsioni regionali, 2019-2026

Mercato dei dispositivi per neuroendoscopia Analisi delle dimensioni, della quota e dell'industria, per tipo di prodotto (neuroendoscopi rigidi, neuroendoscopi flessibili), per tipo di applicazione (neuroendoscopia transnasale, neuroendoscopia intraventricolare, neuroendoscopia transcranica), per utente finale (ospedali, cliniche specializzate, altri) e previsioni regionali, 2019-2026

Mercato di sequenziamento di nuova generazione (NGS) Dimensioni, quote e analisi del settore per tipo (prodotti, strumenti e software, materiali di consumo, servizi), per applicazione (diagnostica, ricerca), per utente finale (istituti di ricerca, strutture sanitarie e centri diagnostici, società farmaceutiche e biotecnologiche, organizzazione di ricerca a contratto) E previsioni regionali, 2019-2026

Mercato della medicina rigenerativa Dimensioni, quota e analisi del settore per prodotto (terapia cellulare, terapia genica, ingegneria tissutale, plasma ricco di piastrine), applicazione (ortopedia, cura delle ferite, oncologia), canale di distribuzione (ospedali, cliniche) e previsioni regionali, 2019-2026

Mercato della genomica Dimensioni, condivisione e analisi del settore per tipo (prodotti, servizi), tecnologia (reazione a catena della polimerasi, sequenziamento di prossima generazione, microarray, sequenziamento di Sanger), applicazione (diagnostica, ricerca), utente finale (istituti di ricerca, strutture sanitarie e centri diagnostici , Aziende farmaceutiche e biotecnologiche, organizzazione di ricerca a contratto (CRO)) e previsioni regionali, 2019-2026

Mercato dei servizi della Contract Research Organization (CRO) Dimensioni, quote e analisi del settore per tipo di servizio (scoperta, servizi preclinici, clinici, di laboratorio), per applicazione (oncologia, cardiologia, malattie infettive, disturbi metabolici, altro), per utente finale (aziende farmaceutiche e biotecnologiche, società di dispositivi medici , Istituti accademici e di ricerca, altri) e previsioni regionali 2019-2026

Mercato dell'immunologia Dimensione, quota e analisi del settore per classe di farmaci (anticorpo monoclonale (mAb), proteine ​​di fusione, immunosoppressori, anticorpi policlonali (pAb), altri), per indicazione di malattia (artrite reumatoide, artrite psoriasica, psoriasi a placche, spondilite anchilosante, malattia infiammatoria intestinale, Profilassi del rifiuto d'organo, altri), per canale distributivo e previsioni regionali 2019-2026

Mercato immunodiagnostico Dimensioni, quota e analisi del settore per strumenti di prodotto, reagenti e materiali di consumo), per applicazione (oncologia ed endocrinologia, epatite e retrovirus, marker cardiaci, malattie infettive), per utente finale (laboratori clinici, ospedali, uffici medici), per utente finale (Ospedali, cliniche dentali, istituti accademici e di ricerca) e previsioni regionali, 2019-2026

Mercato Ortobiologico Analisi delle dimensioni, della quota e del settore per tipo di prodotto (viscosupplementi, stimolatori della crescita ossea, matrice ossea demineralizzata, sostituti ossei sintetici, cellule staminali, allotrapianti), per applicazione (fusione spinale, maxillo-facciale e dentale, riparazione di tessuti molli, chirurgia ricostruttiva e di frattura), Per utente finale (ospedali, centri di chirurgia ambulatoriale, cliniche specializzate) e previsioni regionali 2019-2026

Riguardo a noi:

Fortune Business Insights ™ offre analisi aziendali esperte e dati accurati, aiutando le organizzazioni di tutte le dimensioni a prendere decisioni tempestive. Adattiamo soluzioni innovative per i nostri clienti, aiutandoli ad affrontare le sfide distinte per le loro attività. Il nostro obiettivo è fornire ai nostri clienti informazioni di mercato olistiche, offrendo una panoramica granulare del mercato in cui operano.

I nostri report contengono un mix unico di intuizioni tangibili e analisi qualitative per aiutare le aziende a raggiungere una crescita sostenibile. Il nostro team di analisti e consulenti esperti utilizza strumenti e tecniche di ricerca leader del settore per compilare studi di mercato completi, intervallati da dati rilevanti.

A Fortune Business Insights ™ miriamo a evidenziare le opportunità di crescita più redditizie per i nostri clienti. Pertanto, offriamo raccomandazioni, rendendo più semplice la navigazione tra i cambiamenti tecnologici e di mercato. I nostri servizi di consulenza sono progettati per aiutare le organizzazioni a identificare opportunità nascoste e comprendere le sfide competitive prevalenti.

Contattaci:
Fortune Business Insights ™ Pvt. Ltd.
308, sede suprema,
Sondaggio n. 36, Baner,
Autostrada Pune-Bangalore,
Pune – 411045, Maharashtra, India.
Telefono:
Stati Uniti: +1 424253 0390
Regno Unito: +44 2071 939123
APAC: +91 744740 1245
E-mail: sales@fortunebusinessinsights.com
Fortune Business Insights ™
LinkedIn | cinguettio | Blog

Comunicato stampa: https://www.fortunebusinessinsights.com/press-release/in-vitro-fertilization-ivf-market-9606

Semi di canapa sono essenziali nell'industria farmaceutica e farmaceutica poiché sono una delle migliori fonti di proteine ​​vegetali, acidi grassi essenziali e contenuto di fibre. Hanno la capacità di migliorare la salute del cuore, innescare la digestione, costruire massa muscolare, curare l'anemia, eliminare l'insonnia e sovvenzionare i problemi di perdita di peso. Quindi, prima di approfondire ulteriormente, diamo un'occhiata da vicino e proviamo a capire:

La canapa, popolarmente conosciuta come canapa industriale, è una variante genetica della Cannabis Savita Plant. Sono coltivati ​​per la sua rafia fibra o i suoi semi commestibili, qui la fibra di rafia indica il materiale peloso di una pianta che è la corteccia interna di un albero. Quando si tratta di canapa, le persone si confondono sul loro contributo e lo confrontano con una pianta di cannabis che funge da fonte di Marijuana e hascisc. Indipendentemente dal fatto, tutti e tre i prodotti – Canapa, Marijuana e hascisc contiene composizione di tetraidrocannabinolo (THC).

La quantità di cannabis utilizzata per la formazione di Canapa contiene meno quantità di THC rispetto a quella utilizzata nella produzione di marijuana e hashish. Per capire meglio in che modo differiscono l'uno dall'altro, daremo un'occhiata a:

Struttura chimica dei semi di canapa:

Canapa è un'angiosperma che appartiene alla famiglia della cannabis e può essere facilmente coltivata in climi temperati, buone condizioni del suolo, fertilizzanti e acqua senza pesticidi ed erbicidi. Il raccolto viene raccolto per quasi 120 giorni (4 mesi) fino a raggiungere un'altezza di 10-15 piedi.

Canapa i semi contengono approssimativamente il 30% di carboidrati, il 25% di proteine, il 15% di fibre insolubili, il carotene, il potassio, il fosforo, il magnesio, lo zolfo, il calcio, il ferro e lo zinco. È rinomata per essere una delle migliori fonti di acidi grassi essenziali con il perfetto equilibrio tra acidi grassi Omega-3 e Omega-6.

La variazione di composizione di canapa il seme è diviso in diversi fattori, alcuni dei quali sono elencati di seguito in un formato tabulare:

1.1 Analisi prossimale dei semi di canapa:

1.2 Proprietà fisiche dell'olio di semi di canapa:

1.3 Proprietà chimiche dell'olio di semi di canapa:

Quindi, dai dati di cui sopra, puoi vedere come Semi di canapa agire come una fonte di fattori nutritivi essenziali rispetto ad altri membri della famiglia della cannabis.

Importanza dei semi di canapa come medicinali:

Secondo la storia, varie parti della pianta di cannabis sono state elaborate per la formazione di Canapa, Marijuana, e hascisc che contengono componenti THC in quantità specifiche. Il THC è un composto che può creare un impatto pericoloso sul tuo corpo in quantità maggiori.

Ma in Canapa semi, la quantità di THC è bassa rispetto ad altre forme di droga come Marijuana e hascisc ed è per questo Canapa i semi sono trattati come super-alimenti sani. Canapa i semi sono ricchi di acidi grassi Omega-3 e Omega-6 nel cui rapporto è noto per essere un anti-farmaco contro malattie cardiache, cancro, diabete e carenze autoimmuni.

Questi colori verde brillante Canapa i semi contengono circa il 90% di acidi grassi polinsaturi. Con questo abbiamo sviluppato una buona comprensione del perché Canapa i semi sono considerati la migliore fonte di acido grasso, quindi ora esaminiamo i loro benefici:

I 10 principali benefici nutrizionali dei semi di canapa ?:

Parlando dei benefici, Canapa i semi sono stati usati per più di migliaia di anni nell'industria medicinale. Sono utilizzati in varie medicine tradizionali e integratori alimentari a causa dei loro effetti positivi e sono molto vitali nel trattamento di diverse condizioni di salute. Diamo un'occhiata ai benefici per la salute di Canapa semi in modo più dettagliato di seguito:

1. Ricco di contenuto proteico:

La ragione per cui Canapa i semi sono utilizzati nelle industrie medicinali a causa del suo ricco contenuto proteico. Contiene tante proteine ​​quanto i semi di soia (che è anche una buona fonte di proteine) i, e. In ogni 30 grammi di semi o 3 cucchiai di Canapa i semi possono contenere contenuto proteico di 9.46 grammi.

Sono considerate la migliore fonte di proteine ​​contenente tutti e nove gli aminoacidi essenziali. Un corpo umano non può formare tutti i nove amminoacidi essenziali che sono i mattoni delle proteine, quindi questa è la ragione Canapa i semi vengono assorbiti attraverso la dieta per ottenere un contenuto proteico sufficiente. L'arginina presente in Canapa i semi grazie alla presenza di aminoacidi migliorano la salute del cuore.

2. Migliora la salute del cuore:

I semi di canapa hanno un impatto maggiore quando si tratta di salute del cuore in quanto possiede una vasta gamma di opzioni di cura tra cui un corretto equilibrio del livello di colesterolo o acidi grassi nel corpo. Canapa i semi contengono il rapporto corretto di acidi grassi Omega-3 e Omega-6 che è di circa 3: 1.

Come suggerisce la ricerca, Canapa i semi sono unici nel loro genere e contengono già l'equilibrio perfetto. Per il normale funzionamento del corpo, il livello di grassi saturi nel corpo è molto essenziale in quanto

• Previene l'aterosclerosi
• Riduce gli infarti e gli ictus
• E molti altri problemi legati al cuore.

Canapa i semi hanno un alto contenuto di fibre che aiuta a eliminare il colesterolo in eccesso dalle pareti delle arterie.

3. Potenzia il sistema digestivo:

Secondo un diario di ingegneria, un rapporto afferma che Canapa i semi sono una meravigliosa fonte di fibre alimentari solubili e insolubili. Il ruolo principale delle fibre insolubili è quello di ammassare le feci e facilitare il passaggio attraverso il percorso digestivo, riducendo quindi i sintomi di diarrea e costipazione.

D'altro canto, le fibre solubili sono soggette a rallentamento del processo di assorbimento del glucosio e aumento dei succhi digestivi e gastrici. La combinazione di questo tipo di fibre nel tuo corpo può aiutarti a evitare problemi di salute da lievi a gravi.

4. Aiuta a alleviare l'insonnia:

Uno dei ruoli più importanti e vitali che Canapa il seme gioca in presenza di un alto contenuto di minerali con l'inclusione del magnesio che tende a creare una sensazione rilassante e rilassante in tutto il corpo.

La presenza di magnesio nel corpo ha diversi benefici per la salute e ormoni che sono responsabili di indurre il sonno.

Uno studio è stato recentemente pubblicato affermando che la serotonina viene prodotta quando il magnesio è amministrato nel corpo e viaggia fino al cervello che a sua volta viene convertito in melatonina (un potente aiuto per il sonno che ti dà una sensazione rilassante e rilassante). Questo è il motivo per cui Canapa i semi sono raccomandati per i pazienti con insonnia.

5. L'olio di canapa può alleviare il disturbo della pelle:

Gli studi suggeriscono che il perfetto equilibrio di acidi grassi Omega-3 e Omega-6 nel corpo aiuta il sistema immunitario a rimanere in forma a lungo termine. Olio di canapa e Semi di canapa sono una buona fonte di acidi grassi polinsaturi ed essenziali.

Il rapporto tra Omega-3 e Omega-6 che ottieni Canapa i semi sono nel rapporto 3: 1 che è della gamma ottimale.

applicando Olio di canapa alla tua pelle ti aiuterà a prevenire problemi legati alla pelle come:

• Eczema
• Acne
• Psoriasi
• Lichen Planus

Sulla base di queste malattie sopra indicate, Canapa l'olio può agire come un'ottima fonte di integratori e può contribuire a una pelle più sana, più forte e catartica che è più resistente alle infezioni virali, batteriche e fungine.

6. Tratta l'anemia:

Puoi trovare ferro dentro Canapa semi che è considerato come uno dei principali contenuti minerali che è parte integrante della formazione della costruzione dei globuli rossi nel corpo umano.

Se il tuo corpo è carente nella formazione di ferro, allora è probabile che potresti soffrire di anemia.

Qui è dove l'assorbimento di Canapa i semi entrano in gioco in quanto contengono la giusta quantità di contenuto di ferro per impedire al corpo di soffrire di anemia.

7. Aumenta la massa muscolare e la crescita muscolare:

Sei un bodybuilder o una persona che sta cercando di guadagnare una buona quantità di fibre muscolari? Canapa seme proteine ​​in polvere è ciò di cui hai bisogno per guadagnare massa muscolare.

Sì, hai sentito bene Canapa i semi contengono tutti e nove gli aminoacidi essenziali che sono considerati i mattoni delle proteine ​​del tuo corpo e proteina è l'elemento chiave necessario per la crescita e la riparazione dei muscoli.

Ecco i nove amminoacidi essenziali di cui stavamo parlando:

• istidina
• isoleucina
• leucina
• lisina
• metionina
• fenilalanina
• treonina
• Triptofano
• valina

8. L'olio di canapa allevia l'artrite:

I ricercatori e molti altri portali di ingegneria lo affermano Canapa l'olio può svolgere un ruolo vitale nel trattamento di qualcuno che soffre di artrite. Quasi il 15% degli americani soffre di questo dolore cronico.

I tipi più comuni di artrite sono:

• Artrite reumatoide (RA): – Questo è un tipo di malattia autoimmune causata nel sistema immunitario di una persona che tende ad attaccare le articolazioni formando infiammazione. Questo tipo di artrite colpisce generalmente le mani e i piedi di una persona e porta a articolazioni dolorose, rigide e gonfie.
• Artrosi (OA): – Questo è un tipo di artrite che colpisce la cartilagine articolare e le ossa causando dolore e rigidità. Questi sono problemi comuni che possono insorgere nel corpo umano che colpiscono le articolazioni dell'anca, del ginocchio e del pollice.

Canapa l'olio è qualcosa che tende a svolgere un ruolo vitale nel sistema immunitario di un corpo umano gestendo il dolore e l'infiammazione. Lo scienziato crede, usando Canapa l'olio potrebbe svolgere un ruolo importante nella gestione del dolore cronico.

9. Cura capelli, pelle e unghie:

Dai semi di canapa, possiamo ottenere Canapa olio che viene ampiamente utilizzato nei prodotti cosmetici e per la cura della pelle a causa dei suoi effetti rassicuranti su varie condizioni della pelle come dermatite, eczema, psoriasi, infiammazione della pelle e molti altri.

Ecco alcuni degli effetti che Canapa i semi cercano di migliorare:

• Ipertensione: La presenza di nove aminoacidi essenziali nell'olio di canapa tende alla formazione di induzione proteica chiamata idrosilato che abbasserà la pressione sanguigna prevenendo così il rischio di ictus e malattie cardiache.
• Riduce la ricorrenza di alcol e droghe: L'olio di canapa è anche noto come olio di cannabidiolo che è un componente non psicoattivo della pianta di cannabis Savita può anche essere usato come scudo per combattere l'alcolismo e contenere le voglie di cocaina.
• Regola gli ormoni: canapa: I semi contengono acido gamma-linoleico che funge da regolatore ormonale per coloro che soffrono di tiroide e pancreas. Aiuta anche a regolare lo squilibrio ormonale.

10. Riduce lo stress e l'ansia:

Ansia, stress e sbalzi d'umore sono sintomi comuni con cui l'uno o l'altro è interessato. Olio di semi di canapa può un prezioso anti-dose per i pazienti chiropratici e tende a curare i disturbi dell'umore.

Se stai seguendo una dieta ricca di proteine, ti aiuterà a superare il disturbo e olio di semi di canapa contiene tutti i minerali e le proteine ​​vitali necessari per alleviare lo stress e l'ansia.

Questi sono alcuni dei punti vitali e più importanti sopra elencati per darti una conoscenza approfondita dei suoi benefici.

Ora, non possiamo semplicemente parlare di tutti i benefici piuttosto che dichiarare alcuni degli effetti collaterali che potrebbe causare, quindi qui potrai presentare alcuni dei pochi effetti collaterali, che Semi di canapa potrebbe causarti:

Effetti collaterali:

Ci sono effetti collaterali minimi associati ai semi di canapa, se si soffre di una sorta di interazione farmacologica, è probabile che possa aumentare il rischio di sanguinamento se assunto insieme agli anticoagulanti.

Un'altra cosa che dovresti tenere a mente, se sei incinta o porti un bambino, si consiglia di consultare il medico che ti guiderà con i farmaci adeguati durante questa fase.

Ora abbiamo finito con tutti i possibili risultati che un seme di canapa può fornirci e siamo vicini all'ultimo possibile stadio del nostro conclusione, Scopriamolo:

Perché dovresti prendere in considerazione l'uso di prodotti a base di semi di canapa?

Come sei consapevole del fatto, quello Semi di canapa sono una potente fonte di proteine ​​con tutti e nove gli aminoacidi essenziali che contengono il rapporto perfetto tra acidi grassi Omega-3 e Omega-6 di un rapporto 3: 1.

Questi semi di canapa sono considerati la pianta più nutriente del mondo e una fonte vitale di proteine ​​per vegani e crudisti. I semi di canapa sono utilizzati anche in numerosi prodotti alimentari e integratori, tra cui Latte di canapa, Proteine ​​in polvere, burro, prodotti insaturi e molti altri.

Non solo prodotti alimentari, ma utilizzando Olio di canapa ti tiene lontano da problemi legati alla pelle per citarne alcuni:

• Eczema
• Acne
• Psoriasi
• Lichen Planus

Ti aiutano a prevenire Artrite reumatoide, artrosi, e molti altri dolori associati alle articolazioni.

Questi Piante di canapa sono considerate le piante più intraprendenti e sostenibili del pianeta con tutte le sue caratteristiche positive e nutrizionali.

Con i suoi numerosi benefici, Semi di canapa stanno alimentando l'ambiente globale con i suoi aiuti nutrizionali.

Image source: The Motley Fool.

Bausch Health Companies Inc. (NYSE:BHC)
Q4 2019 Earnings Call
Feb 19, 2020, 8:00 a.m. ET

Contents:

• Prepared Remarks
• Questions and Answers
• Call Participants

Prepared Remarks:

Operator

Good day and welcome to the Bausch Health Fourth Quarter and Full-Year 2019 Financial Results Conference Call. All participants will be in a listen-only mode. (Operator Instructions) After today’s presentation, there will be an opportunity to ask questions. (Operator Instructions) Please note this event is being recorded.

I would now like to turn the conference over to Arthur Shannon, Senior Vice President of Investor Relations and Global Communications. Please go ahead.

Arthur J. Shannon — Senior Vice President and Head of Investor Relations and Communications

Thank you, Alicia. Good morning, everyone, and welcome to our fourth quarter and full-year 2019 financial results conference call. Participating on today’s call are Chairman and Chief Executive Officer Mr. Joe Papa and Chief Financial Officer Mr. Paul Herendeen. In addition to this live webcast, a copy of today’s slide presentation and a replay of this conference call will be available on our website under the Investor Relations section.

Before we begin, we’d like to remind you that our presentation today contains forward-looking information. We would ask that you take a moment to read the forward-looking statement legend at the beginning of our presentation as it contains important information. This presentation contains non-GAAP financial measures. For more information about these measures, please refer to Slide 2 of the presentation. Non-GAAP reconciliations can be found in the appendix to the presentation posted on our website. Finally, the financial guidance in this presentation is effective as of today only. It is our policy to generally not update guidance until the following quarter and not to update or affirm guidance other than through broadly disseminated public disclosure.

With that, it’s my pleasure to turn the call over to Joe Papa.

Joseph C. Papa — Chairman of the Board and Chief Executive Officer

Thank you, Art, and thanks everyone on the phone for joining us today. Let’s quickly review the topics we will cover today. I’ll begin with a brief summary of our 2019 Company highlights before turning the call over to Paul Herendeen, our CFO. Paul will take us through the fourth quarter and full-year financial results and provide our 2020 guidance. I’ll then review the segment highlights and catalysts before opening the line for questions.

Beginning on Slide 4, in 2019, our theme was pivot to offense or focus on driving organic growth in our core businesses. We have now delivered eight consecutive quarters of organic growth and 2019 was our first full year of reported revenue growth since 2015. Bausch Health grew organically by 4% in 2019 and reported revenues were up 3%. Our largest segment, B&L International delivered its third consecutive year of mid-single-digit organic revenue growth. Salix reported full-year revenue of more than $2 billion for the first time ever. We generated $1.5 billion of cash from operations. We increased R&D investment by 14% compared to 2018 and we used approximately $1.1 billion of cash to pay down roughly $900 million of debt and fund approximately $250 million of bolt-on acquisitions or licensing products. Pivoting to offense also include launching new products and driving their growth and our new products continue to grow.

First, following the launch of Thermage FLX in Asia Pacific, the Thermage franchise saw 73% organic revenue growth compared to 2018. This exceptional growth rate made the Thermage one of the Bausch Health’s Top 10 franchises in 2019. Lumify achieved a weekly market share of approximately 43% in 2019, is the Number 1 physician-recommended product in the redness reliever category. Trulance TRxs grew by 31% year-over-year and we have improved the market access position for approximately 35 million lives since we acquired the product in the first quarter of 2019. Duobrii has been another standout. Weekly TRxs grew by 25% from the third quarter to the fourth quarter of 2019 and we have now achieved 63% commercial access. Overall, the entire Bausch Health team of 22,000 employees delivered on our promise to pivot to offense in 2019 and demonstrated the durability of our business, which we grew both organically and through strategic bolt-on acquisitions. Great effort by the entire Bausch Health team.

Paul’s going to walk you through the fourth quarter and full-year results in more detail. So with that, I’ll turn it over to Paul.

Paul S. Herendeen — Executive Vice President and Chief Financial Officer

Thanks, Joe. A lot to cover. I’ll try to go fast. Good quarter and a good year, a little different approach this quarter. I’m going to start with Slide 5, a summary of the changes in revenue by segment and major business units for both Q4 and the full-year 2019. I’ll then walk down the top level P&L for the quarter and provide some observations about the full year before turning to our guidance for 2020. Quick reminder, when we talk about organic growth, that means excluding the impact of changes in FX rates, the impact of divested and discontinued businesses in the prior-year periods and the impact of acquired businesses.

Okay, Slide 5. In the quarter, we posted 4% organic revenue growth versus Q4 of 2018. Recall that last year we took steps to reduce our channel inventories held at wholesalers and that that had the effect of reducing Q4 ’18 revenue by an estimated $76 million. So, that’s a tailwind for us this quarter. Excluding the impact of the inventory contraction, we still posted top level organic revenue growth of plus 1%. There were a lot of moving parts, but a lot of good stuff within each of our segments.

Let’s start with Salix as it was the largest contributor of organic revenue growth in the quarter, up 17% organically on continued strong performance from Xifaxan, up 29%. Relistor up 29% and Plenvu also contributed growth. We lost exclusivity for Apriso in the quarter and that combined with the continued generic erosion of Uceris offset some of the growth. While not a factor in organic growth, Trulance sales totaled $18 million in the quarter and Salix TRxs were up 69% versus Q4 of ’18. A strong quarter from Salix to wrap up a great year, posting 13% organic revenue growth for the full year versus 2018, despite LOEs.

B&L International segment revenue was up 3% organically in the quarter led by Global Consumer plus 7% organically on strength in Lumify in the US and our global contact lens solution brands Renu and Biotrue Multi-Purpose. Global Surgical was plus 5% organically in the quarter on strength in consumables for the back of the eye and enVista IOLs. Global Vision Care was plus 4% organically in the quarter on strength in ULTRA monthly silicone hydrogel lenses, our AQUALOX Daily SiHy lenses in Japan and Biotrue ONEday lenses. Our international pharma business was essentially flat versus Q4 of ’18 while Global Ophtho Rx declined 2% organically as growth of Vyzulta and Prolensa were more than offset by the decline of the Lotemax brand family due to generic erosion.

For the full year, B&L International grew 5% organically, consistent with our belief that this diverse and durable segment can deliver mid-single-digit growth over time. All five of the B&L International business units posted organic revenue growth for the year, led by Global Consumer up 6% organically on strength of Lumify in the US and our eye vitamins globally, followed by Global Vision Care up 7% organically, with contributions from our Biotrue ONEday lenses, our monthly ULTRA lenses and our AQUALOX Daily SiHy lenses in Japan.

Our international pharma business was up 5% organically on strength in Russia, Egypt and Canada. Global Ophtho Rx was up 2% organically. Unlike in the quarter, for the full year, growth of Vyzulta, Prolensa and a portfolio of our international ophthalmic brands overcame the LOE drag from Lotemax. The Ortho Dermatologics segment declined 1% organically in Q4 of ’19 versus ’18 as spectacular growth in our global aesthetics business Solta, which was up 42%, nearly overcame the 18% decline in medical dermatology. In the Solta business, the Thermage platform is now solidly in the Top 10 products for the entire company and was a significant contributor to companywide growth. LOEs played a big role in the quarterly decline in medical derm, mainly Elidel and Zovirax cream. The balance of promoted products in medical derm including Duobrii, Jublia, Siliq and Bryhali, all grew versus Q4 of 2018. It’s pretty much the same story for the Ortho Derm segment for the full year, strong growth from Global Solta plus 45% organically for the year, more than offset by the decline in medical dermatology. For the full year, medical derm was our business most impacted by LOEs, a minus $121 million growth drag versus 2018.

On the plus side, Jublia was one of the Top 15 contributors to companywide revenue growth in 2019 versus ’18. As the impact of LOEs moderate in this segment, Jublia, together with our brands in growth phase, that’s Duobrii, Siliq and Bryhal, form the core of our medical derm portfolio and the basis for an expected return to growth in this business in 2020.

Finally, the Diversified segment, which declined 5% organically in the quarter as LOEs were a $29 million (Phonetic) drag on the neuro business. Our generics business grew 3% organically in the quarter with authorized generic versions of our branded products that lost exclusivity, mainly Uceris, Apriso, Lotemax and Elidel providing the bulk of that growth. For the full year, Diversified declined 5% organically as a 11% growth of our generics business offset some of the $116 million LOE growth drag in our neuro business.

Total company revenue for the year grew 4% organically, with 2% coming from improved realized net selling prices and 2% from increased volume.

Flip to Slide 6, the P&L summary for the quarter. Our gross margin in the quarter was 71.4%, down about 20 basis points versus Q4 of 2018, mainly due to higher inventory write-offs in Q4 ’19 relative to the prior-year quarter. Note that for the full year, our gross margin was 72.7%, favorable by 80 basis points versus 2018 with mix a big driver, particularly impacted the growth of Xifaxan, but also from improvements associated with our Project CORE activities. Our final guidance for the full year for gross margin was roughly 73%.

Selling and advertising expenses in the quarter were up — are unfavorable on a constant-currency basis by 6% versus Q4 of 2018 due to the addition of Trulance to the Salix portfolio and higher A&P costs in Vision Care to support new launches and in international pharma for product launches, particularly in Canada and Russia. Adjusted G&A expenses on a constant-currency basis were 8% unfavorable in the quarter compared to Q4 of 2018 due to increased cost of business development initiatives and higher ongoing IT costs as we continue to work to improve our global operating systems. I want to point out that in Q4 of 2019, adjusted G&A run rate, is above what I would expect on average the quarterly run rate to be in 2020. The go-forward adjusted G&A run rate is likely between the $163 million we saw in Q4 and the $140 million average over the first three quarters of 2019. R&D was down in the quarter or favorable by 5% on a constant-currency basis. I would not read much into that. It’s just how the timing of expenses fell in both periods. For the full year, R&D was up 15% on a constant-currency basis to $471 million, slightly below our final 2019 guidance for R&D of $480 million. Again, just the timing of how expenses fell. As you’ll see when I get to 2020 guidance, we intend to commit more capital to R&D activities.

Adjusted EBITDA in the quarter was $898 million, up 5% from the year-ago quarter on a constant-currency basis, a solid quarter that enabled us to post adjusted EBITDA of $3.571 billion for the full year, which was plus 4% on a constant-currency basis from 2018 and just below the top end of our final guidance range for 2019.

Turning to Slide 7. I think it’s worth taking a look back at how we did in 2019 relative to the midpoint of our original 2019 guidance, which was $8.4 billion of revenue and $3.425 billion of adjusted EBITDA. Our actual 2019 revenue was $201 million above the midpoint of original guidance with a favorable result a function of four things. The acquisition of Trulance added $55 million, revenue from LOE assets was plus $53 million, our base business was favorable by $115 million, and offsetting the good guys, changes in FX rates reduced revenue by some $22 million. Adjusted EBITDA was $146 million above the midpoint of our original guidance. FX had no impact, Trulance had no impact, the better LOE revenue has added $36 million of profit, the better base performance added $71 million of profit, while investment in R&D and SG&A spending were both a bit above our original view. The biggest single factor in the improved adjusted EBITDA was our gross margin coming in at 120 basis points better than initially forecast, which accounted for roughly $100 million of lift. Point of the story is that, as the year played out, we had some good fortune with the LOE assets, but the lion’s share of the better results came from our commercial units driving improved performance in our base businesses, from our Project CORE activities to improve gross to nets, and from our relentless efforts to improve efficiency in our supply chain, a good year.

Turn to Slide 8, the cash flow summary. Our net cash provided by operating activities in 2019 came in at $1.501 billion, the low end of our expected range as we increased inventories of certain key products and API to ensure uninterrupted supply. Note that at year end, we had $3.244 billion of cash on hand as we completed an offering of $2.5 billion of unsecured notes in late December and had not yet applied those proceeds to the payment of the US Securities Litigation, that’s $1.21 billion and the prepayment of other debt totaling $1.24 billion. Net of those amounts and related fees, our working cash at year end was roughly $750 million.

Similarly on Slide 9, the cash and debt on our balance sheet at year end are inflated due to the timing of the $2.5 billion debt raise and the use of those net proceeds. I think of it like this. Pro forma for the deployment of those funds, our net debt at year end would have been roughly $24.2 billion. Settling the US Securities case, set us back in our progress reducing the quantum of our debt and improving our leverage ratios, but it was absolutely the right thing to do to quantify and settle a significant overhanging uncertainty. Quick aside, just last week, we began the process of calling another $100 million principal amount of bonds. We intend to continue to systematically grind our debt down. One last thing on the balance sheet. During the quarter, we accrued for the settlement of the US stock drop case, other related cases, and ongoing legacy litigation and investigations. The total accrual was for $1.39 billion and is included in GAAP other income and expenses in our P&L. For the avoidance of doubt, we exclude this expense from the computation of adjusted EBITDA and adjusted net income.

Finally and onto the money slides for me, starting with Slide 10, showing our guidance for 2020. Our revenue guidance for 2020 is a range of $8.65 billion to $8.85 billion and that represents a range of growth of plus 1% to plus 3% at current FX rates. Our adjusted EBITDA guidance is a range of $3.5 billion to $3.65 billion, representing a range of growth of minus 2% to plus 2% at current FX rates. I want to cover the other elements of our guidance on this slide before talking about how to think about those revenue and profit growth rates for 2020.

Adjusted SG&A expenses were $2.5 billion in 2019 and we’re guiding to approximately $2.6 billion for 2020. The roughly $100 million or 4% increase is higher than it may be as we look ahead to 2021 and 2022. In our 2020 plan, we rationalized opex across several business units, but we also allocated incremental selling, advertising and promotional resources to some units to support launch products and products in launch phases, including Daily SiHy lenses, Lumify, Duobrii, and Thermage.

In G&A, we are continuing to build out our global IT organization and infrastructure and that comes at a cost, increasing our adjusted G&A in 2020 versus 2019. As we move forward into 2021 and 2022, we should be able to hold the growth of SG&A below that of revenue growth. We’re guiding to roughly $500 million in R&D for 2020, up roughly $30 million from 2019. If you go back to 2017, our investment in R&D totaled $361 million. Over the last few years, we’ve built up the R&D organization and infrastructure to support an increased volume of product to sustain each of our core businesses. That includes reducing the investment intensity in some areas, while increasing commitments to other areas where we had been underinvested over a number of years and that’s specifically GI, B&L Surgical and Optho Rx. While a 6% increase in R&D reduces our near-term earnings and earnings growth, it’s the right thing to do to enhance our prospects to deliver long-term organic growth.

For interest expense, we’re guiding to $1.55 billion, down from $1.6 billion, despite the addition of $1.21 billion of debt to fund the settlement of the US Securities class action. Our tax rate on adjusted earnings was 7.8% in 2019. We expect that rate to be about the same, roughly 8% in 2020. Towards the bottom of the page, note that we’re guiding to capital expenditures in 2020 of roughly $300 million. In the past, I’ve said that our steady state capex might be roughly $160 million to $175 million per year and that the uptick in 2019 was mainly due to investments in connection with the daily silicone hydrogel lens initiative and our build-out of our global IT systems. Over time, we’ve determined that under investment, particularly in our supply chain over the last number of years, necessitate increased investment in 2020 and beyond. It’s our current view that after roughly $300 million of investment in 2020, we will likely see capex requirements decrease in 2021 and again in 2022 are steady state, a few years out, maybe closer to $225 million of capex per year.

Contingent consideration milestones and license agreements totaled $58 million in 2019 and we’re guiding to roughly $100 million in 2020. The increase was related to a forecast sales milestone on Relistor and payments related to the recently acquired rights to Xipere and NOV03.

Finally, restructuring and other. In 2019, these items totaled $52 million. In 2020, we’re guiding to $75 million. I’d point out that this item represents our estimate of restructuring costs, some systems integration and settlement of legal cases and investigations.

Turning to Slide 11, the bridge from 2019 actual results to our 2020 guidance. First, focus on the LOE impact. We are forecasting a $275 million of growth drag from the basket of LOE assets in 2020. The good news here is that we are finally close to putting the impact of the large bucket of LOEs behind us. In 2007 (Phonetic) versus ’16, the growth drag was $486 million. In ’18 versus ’17, it was $289 million. In ’19 versus ’18, it was $360 million. Over the last three years, our revenue growth was trammeled by more than $1.1 billion of LOE drag. In 2020, we expect the drag to moderate to $275 million. And here is the good part. That’s based on us realizing revenues on the LOE basket of $237 million in 2020 and while that amount will decline into 2021 versus 2020, the drag will be substantially reduced. We did not add any new LOEs to the LOE basket in 2020. And looking out over the period from ’21 to ’23, we expect the impact of future LOE assets to be quite manageable.

The base performance of plus a $100 million — excuse me, $415 million is impacted in negative ways by a few things that I called out on our last call and a few others worth noting. First, there is the non-recurrent portion of the improvements in gross to nets that we saw in 2019 and especially in Q3 that are a headwind to 2020 growth. Next, the trajectory of the — is the trajectory of Glumetza. Glumetza had been a strong performer through the first three quarters of 2019 before as we forewarned, it dropped almost in half in Q4 and is now expected to trend downward from there in future quarters. Next and one I had not previously called out for you, we had terrific performance in our generics business in 2019 with major contributions from the authorized generic versions of Uceris and Elidel. As more generic versions of these products have launched, we will see significant declines in revenue for our AGs in 2020. Think of the AGs as us stretching the tail of brands that lose exclusivity. It’s good, but it’s fleeting.

One other bit of color. The base performance could have been better, but our guidance includes an estimate of a meaningful headwind on our Asia-Pac region, especially China, associated with the coronavirus situation. Our revenue guidance includes a roughly $50 million coronavirus impact. That’s an estimate and we’ll see how this plays out over 2020. Obviously this impacted our adjusted EBITDA guidance as well. So, these items are part of the reason why the revenue growth in 2020 implied by guidance is only in the range of 1% to 3% at current FX rates.

Turning to the EBITDA bridge at the bottom of the page, the currency LOE in R&D impacts are self-explanatory. Within the base performance, we’re absorbing the roughly $100 million or 4% increase in SG&A and the coronavirus impact on our revenue expectations impacts our adjusted EBITDA as well. All these items together are drivers of the adjusted EBITDA growth rates implied by our guidance ranges being below that of our revenue growth rate.

That’s it for me. Back to you, Joe.

Joseph C. Papa — Chairman of the Board and Chief Executive Officer

Thank you, Paul. On Slide 12, there is a lot of information, but the important message to highlight is we have now delivered three consecutive years of mid-single-digit organic revenue growth for B&L International. B&L International was up 6% in 2017, up 4% in 2018, and up 5% in 2019.

Turning to Slide 13, Global Vision Care has been a strong performer and I want to highlight two products that have been key drivers of the growth in this business, Biotrue ONEday and ULTRA contact lenses. We’ve shown five-year reported revenue for each in the charts on the bottom of Slide 13. On the left, from 2015 to 2019, Biotrue ONEday lenses had a 22% compound annual growth rate and in organic revenue grew by 23% in 2019. On the right, our ULTRA lenses had a 32% CAGR over the past five years and grew organically by 24% in 2019. We’ve called out the significant milestones that drove incremental growth, including the launches of lenses for astigmatism, presbyopia, and extended wear. This strong performance underscores the durability of these products and the strength of the Bausch & Lomb brand. We are seeing increased market share in US Vision Care. This business gained 1.6 share points to 11% unit share for the month of December 2019 versus a 9.4% share in December 2018. Finally, we plan to launch our daily silicone hydrogel lenses in the US later this year. Silicone hydrogel lenses are one of the fastest growing segments of the content — of its market.

Turning to Slide 14 for an update on Global Consumer, I want to highlight two franchises. First, our top-selling eye vitamin portfolio in the US Ocuvite and PreserVision grew organically by 4% in 2019 and had a CAGR of about 7% from 2015 to 2019. And second, Lumify, the Number 1 physician-recommended product in the redness reliever category had sales of $63 million in 2019 and achieved a weekly market share of approximately 43%.

On Slide 15, we highlighted enVista’s performance in our Global Surgical business. The enVista family of intraocular lenses or IOLs are clear artificial lenses that eye surgeons use to replace a person’s natural lenses when it becomes too cloudy due to a cataract. enVista grew organically by 36% in 2019. The chart below provides enVista’s reported revenue for the past five years, which grew at a 22% CAGR. We also launched an enVista toric in 2019, which we’ve shown on the bottom right. Looking ahead to the 2020 catalysts, we expect to launch an extended depth of focus intraocular lens platform in 2020. With the introduction of this platform, we will be entering the premium IOL segment, outside the US. And finally, we expect to launch a pre-loaded IOL injector platform for enVista IOLs in the second quarter of 2020.

Moving now to Slide 16, before we go through the key highlights for Salix, I want to address two updates. First, after reviewing our GI portfolio in light of market opportunities, we decided to increase promotional focus of Xifaxan and Trulance and have discontinued promoting Doptelet and Lucemyra. Also, we recently received notice that Norwich Pharmaceuticals have filed an ANDA for rifaximin 550-milligram tablets. Alfasigma and Bausch Health will file suit against Norwich, alleging patent infringement and will trigger a 30-month stay of approval. We remain confident in the strength of the 23 patents covering Xifaxan and we will continue to vigorously defend our intellectual property.

The chart on the right shows Xifaxan TRx growth over the past nine quarters. As you can see, TRxs grew by 7% from 2017 (Phonetic) to 2018 and by 8% from 2018 to 2019. For IBS-D specifically, TRxs grew by 15% in 2019 compared to 2018. Moving now to Relistor, TRxs grew by 6% in 2019 and beginning in 2020, we recently improved Relistor’s Oral market access position for more than 50 million lives. Finally, Trulance. TRxs grew by greater than 30% in 2019 and since the acquisition, we have improved the market access position for approximately 35 million lives. We are seeing progress in the IBS-D branded market where Trulance new Rx market share grew by — from 3.9% to 6.4% in 2019.

Onto Slide 17, Ortho Dermatologics. First, Duobrii TRxs were up 25% in the fourth quarter compared to the third quarter and we’re very pleased with this launch. As we show in the chart on the bottom left, within two quarters of launch, Duobrii is capturing approximately 40% of new patients who were started on a first-line branded topical or oral psoriasis product. When you look at Duobrii against these three competitors listed, we believe it gives a perspective on the opportunity for Duobrii and the potential savings that could result from delaying the need to start patients on a biologic. Also, I am delighted to say that Duobrii is now at 63% commercial access for the United States and we gain — as we gain incremental coverage, we expect to reduce couponing support and expect gross to nets will improve over time. Importantly, average selling price increased from the third quarter and we ended the year with a higher ASP. We are clearly moving in the right direction. We are very enthusiastic about the opportunity for Duobrii, primarily because for the first time, we can offer psoriasis patients a topical product with a high potency corticosteroid that they can treat to clearance, rather than being limited to a certain duration of time.

Moving now to Siliq, TRxs grew by 100% in 2019 compared to the prior year and we achieved 67% (Phonetic) commercial access. Bryhali TRxs were up 60% in the second half of 2019 compared to the first half and Bryhali now has 71% commercial access. We believe access rates of 60% to 70% demonstrate that managed care recognizes the value and the efficacy of our psoriasis products in helping to improve patients’ lives. On the right, we highlight a new cash-pay model for our prescription dermatology products in United States that’s now available online at dermatology.com. Telemedicine and e-commerce are available on the platform as of yesterday. Iconic products such as Retin-A will be available on dermatology.com as well as new products like Altreno. The platform was launched with a portfolio of 15 products and we plan to expand the number of cash-pay products over time. We believe that dermatology.com has the potential to meet patient needs and help grow our dermatology business.

Turning to Slide 18, our aesthetics business Global Solta grew organically by 42% in the fourth quarter of 2019 versus the fourth quarter of 2018 and 45% in the full year, driven by the global expansion of Thermage FLX. Thermage is a non-invasive radio frequency therapy that can address the signs of aging skin. You can see the trend in the chart on the left with a 46% CAGR from 2017. Looking ahead to 2020 and beyond, we expect to see continued global expansion for Thermage FLX, including geographic expansion in the EU.

On Slide 19, you can see we have a good number of late-stage development programs in each of our core business segments. We increased R&D investment in 2019 versus 2018 and allocated a greater percentage of our R&D budget to Bausch & Lomb and Salix on a full-year basis. Launching new products will drive our future growth and we are pleased to have active late-stage pipeline of innovative new products with potential to expand our eye health GI in dermatology portfolio.

I’ve talked about some of the programs along the way, but I want to highlight a couple of them in more detail. Before we turn to Slide 20, at the beginning of 2018, we identified the Significant Seven as key drivers of future growth and these seven products grew collectively by 68% in 2019. While we are pleased with that growth, limiting ourselves to seven products and excluding growth products like Biotrue, ULTRA, PreserVision, enVista IOL, Thermage, Aplenzin, Trulance and Xifaxan doesn’t give a complete picture of the expected drivers of our future revenue growth. Accordingly, we will continue to report revenue for our Top 10 products for each business and in overall for Bausch Health, but would no longer report combined revenue for the Significant Seven.

Let’s turn to Slide 20 for additional detail on our promising late-stage programs in GI and eye health. Amiselimod is a late-stage oral compound that targets the S1P receptor, which plays an important role in autoimmune diseases such as inflammatory bowel disease. Approximately 1.6 million Americans currently suffer from IBD and as many as 70,000 new patients are diagnosed in US annually. We entered into an exclusive licensing agreement with Mitsubishi to develop and commercialize amiselimod in April 2019. In January ’20, we completed an FDA-approved cardiovascular clinical trial protocol that compared amiselimod to placebo and moxifloxacin. The primary endpoint demonstrated that amiselimod had no effect on QT interval prolongation and no other secondary safety signals were identified. We expect to initiate a multi-arm, randomized, placebo-controlled Phase 2 study in 2020 in ulcerative colitis for amiselimod.

On Slide 21, we highlight NOV03 which we recently licensed in for the US and Canada. NOV03 is a non-aqueous eye drop for the treatment of dry eye. The prescription dry eye market represents a great opportunity with 6.8% of the US adult population projected to have diagnosed dry eye disease and prevalence will increase with age. If approved, NOV03 will be the first new prescription treatment for dry eye disease with mechanism of action that is different from currently available products. A Phase 2 study has already been completed which showed significant and clinically meaningful improvements in both signs and symptoms of dry eye disease. There is a Phase 3 study under way and we expect to initiate a second Phase 3 study later this year.

To wrap up, on Slide 22, we have provided an overview of the 2020 vision for our three core businesses, which includes both a look back and what has driven performance and a look ahead to what is coming into focus for 2020.

First Bausch & Lomb. We expect mid-single-digit growth to continue for 2020 based on five years of organic revenue growth for ULTRA, Biotrue and Ocuvite and PreserVision and new products like Lumify and Vyzulta. Looking ahead, we see significant opportunities into SiHy launch in the US and EU and the rest of the world, the ramp of our enVista IOL platform and the expected launch of an extended depth of focus for the IOL platform.

Next in Salix, while absorbing the headwinds from Apriso and Glumetza in 2020, our GI business will be based on two years of high-single TRx growth for Xifaxan, increased market share for Trulance, and double-digit growth driven by market access for our Relistor Oral business. In 2020, we are planning to look forward to also the Plenvu ramp-up, continue to develop of new formulations and indications for rifaximin and pipeline expansion including dolcanatide and amiselimod.

Third in Ortho Dermatologics, we expect this business to return to growth in 2020 based on a 73% organic revenue growth for the Thermage franchise, weekly Duobrii TRx growth and increased commercial access, driving improved gross to nets and the continued ramp of launch products including Siliq, Bryhali, and Altreno. Looking head, we see opportunity in building out the cash-pay model with more products, telemedicine and e-commerce and the launch of ARAZLO.

Finally, we continue to expect to deliver on our three-year CAGRs on a constant-currency basis and from the midpoint of 2019 guidance, we expect revenue to grow at 4% to 6% CAGR and adjusted EBITDA to grow at 5% to 8% CAGR.

With that, operator, let’s open up the line for questions.

Questions and Answers:

Operator

(Operator Instructions) The first question today comes from Terence Flynn of Goldman Sachs. Please go ahead.

Terence Flynn — Goldman Sachs — Analyst

Great. Thanks for taking the questions. Maybe two for me. Just wondering at a high level, what’s embedded in your 2020 guidance for net pricing across the portfolio, how that compares to 2019. And then on SiHy, the launch in Japan, I was wondering, any details you can share on market share and then how we should think about pricing, and positioning as you approach the US launch. Thank you.

Joseph C. Papa — Chairman of the Board and Chief Executive Officer

Okay. Let me start on our pricing — net pricing. Our expectation is that we’ll have somewhere in that 2% range approximately. That’s very consistent with what we saw in our 2019 information. Net pricing was approximately 2%. We expect it to be something comparable to that. Now, there will be some variation between product A and product B, but on balance there.

In terms of the SiHy market share gains in Japan, we’re pleased with our initial launch in Japan. There were some issues that we had to deal with as we launched a new product, but on balance, we are pleased with what we’ve seen in terms of that launch and as Paul said in previous quarters are — importantly as we look at the Japan market, we believe the SiHy market as a percentage of Japan is about 15% and is growing by about 31%, so — the SiHy market that is. So, we think it’s an important contributor to growth and will be an important contributor for a long time and also as we launch here in the US later this year. The US is a little smaller percentage of total market in the US. It’s less than I think 13%, but we also see it growing quickly. So, we’re excited about what that means for us. We probably aren’t going to say anything about pricing yet on the SiHy Daily, but I think you could take it that we’ll be competitive with the other products out in the marketplace in the US SiHy Daily business.

Next question, operator?

Operator

(Operator Instructions) The next question comes from David Amsellem of Piper Sandler. Please go ahead.

David Amsellem — Piper Sandler — Analyst

Thanks. I wanted to focus on Xifaxan and looking at the IQVIA retail data in January, it looks like the growth trajectory of prescriptions is a little more muted compared to 2019. So, I’m wondering if there’s any indication that the franchise is maturing in any way and how should we think about the trajectory of volumes for both IBS and AG as we move more into 2020. Thanks.

Joseph C. Papa — Chairman of the Board and Chief Executive Officer

Sure. I’ll start with that one. We always see some normal variation in the early year, especially as patients have the donut hole questions and different reimbursement challenges as we start the year. So, we don’t see anything specifically happening there that is unusual relative to what we’ve seen in the past. I think as you think about trajectory, I mean, if you — one of the comments I made was talking about Xifaxan specifically relative to IBS-D. I remind you that within IBS-D, we were growing, I think, it was mid double digits, somewhere around 15%.

And importantly, we believe the opportunity there is still very significant for us with Xifaxan. I remember that the IBS-D category, for example, has about 9 million — I’m sorry, has about 12 million antispasmodic prescriptions and as we’ve looked at that, we’re less than, let’s call it, 10% of that business. Therefore, we believe we’ve got a great product for IBS-D patients where with the episodic treatment, you can potentially get these patients to just move off of these products like the antispasmodics like Bentyl dicyclomine and actually get relief from — long-term relief from use of Xifaxan. And so, we’re going to continue to promote that area and we continue to expect to see that growth going on into the future to be clear.

Operator, next question?

Operator

Your next question comes from Ken Cacciatore of Cowen & Company.

Ken Cacciatore — Cowen & Company — Analyst

Good morning and congratulations on all the progress. I know from time to time you’re asked about splitting or selling some of the businesses, but I was wondering as you get more credit for your performance in the underlying value of all the entity and everything that you’re doing, your equity is clearly responding. So, just wanted to know strategically how you view your equity. Is it something that you would think about using to deleverage. Is it something you’re thinking about in terms of maybe larger acquisitions? Just wanted to get your thoughts on that. Thank you.

Paul S. Herendeen — Executive Vice President and Chief Financial Officer

Yeah. Thanks for the question, Ken. It’s Paul. Yeah, our equity has responded. It kind of opens the door to potentially using that equity in some way. I’d say that for now, I mean, we have a great deal of runway to continue to run our businesses and using equity to reduce our leverage just based on a quantum of our debt and what it would take in order to make a meaningful change, probably not the path we go down.

Now using equity in the context of a value-generative transaction, obviously, would have to be the right transaction and something we were incredibly excited about, but we would indeed consider that. I want to touch on, because it’s interesting. We haven’t heard the question as often about splitting the Company up over the last, I’d say, several months as the stock has performed better, but I think when you look longer term, the trend in — the overall trend in financial markets is for a preference on the part of investors for pure plays and we own a bunch of great businesses that are today together and I think that they are stronger — we are stronger with those businesses together today in light of our capital structure, but as we look down the road someday, down the road, there may be opportunities to pursue more pure plays with respect to one or more of our businesses, but that’s just something that’s down the road.

Ken Cacciatore — Cowen & Company — Analyst

Thank you.

Joseph C. Papa — Chairman of the Board and Chief Executive Officer

Operator, next question please.

Operator

The next question comes from Umer Raffat of Evercore.

Umer Raffat — Evercore — Analyst

Hi (Technical Issues) my question. I have two if I may, one for you, Joe, maybe both for you Joe, OK. Joe, clearly characterized the pivot to be offense and the EBITDA growth of 5% to 8%, but in light of the guidance for this year and in light of our raging investor debate on whether the base business is truly a growth business in the first place, I’m curious, do you feel strongly that the 5% to 8% CAGR is achievable, especially, this year tracks at the midpoint of the guidance.

And secondly, I was very curious about the S1P1 press release you guys put out in January, not only because I could still never find the trial online anywhere. So, I was curious where it was actually done and — but also, it seemed to me that the issue with the drug was cardiovascular adverse events and not exactly a QT signal. So, I was curious that FDA asked to do a QT study as a clearing event for larger trials? Thank you so much.

Joseph C. Papa — Chairman of the Board and Chief Executive Officer

Okay. So, I’ll start on the first part of the question of what we’re thinking — pivot to offense and guidance, but I am going to also turn it over to Paul who has worked his way through that. And then, I’ll comment on the S1P modulator. So the simple answer to your question on the CAGRs, are we confident, the answer is yes. We continue to look at that revenue guidance of 4% to 6% growth and then the 5% to 8% on the EBITDA as something that is achievable and I’m going to let Paul comment more about that specifically. But the simple answer is yes, and Paul, do you want to make some specific comments, and I’ll come back on the amiselimod.

Paul S. Herendeen — Executive Vice President and Chief Financial Officer

Yeah, sure. I mean and thanks for the question, because we — Umer, because we do get this question a fair amount. Joe said in his remarks. So that’s a refresh of what we meant when we said 4% to 6% and 5% to 8%, it was off the midpoint of our original 2019 guidance at constant currency. If you adjust that, you could come up with a range of targets for 2022 in order to meet that CAGR in the range of say $9 billion — circa $9.4 billion to $9.95 billion at revenue, $3.9 billion to $4.29 billion (Phonetic) for adjusted EBITDA. Yeah, we continue to believe that we can and will produce revenue and adjusted EBITDAs in that range.

I mean, that’s our current belief. Obviously, not a forecast or a bit of guidance that we take lightly. It is fully supported by our bottoms up long-term view of what we think we can do with each of our businesses. I want to point out because people lose sight of this. As I said it was off the midpoint of 2019 guidance. I spent some time in my prepared remarks talking about how we did in 2019 relative to that original midpoint. We did better. So, that helps us along the road. I think people are going to look at our revenue forecast, revenue off of our guidance range of plus 1% to plus 3% and adjusted EBITDA of minus 2% to plus 2%, say, gee, you’re not on track to say — first of all, we’ve said this a million times. It’s not linear and we are focused on where we need to be in 2022 in order to be able to achieve those targets that we set for ourselves and we remain confident that we can achieve those targets. The good news is, we had a great 2019. The bad news is part of that was through LOEs that continued on. We’re delighted to have earned the profit and have generated the cash from those LOEs, but that goes away. And so, it has a bit of a growth track for us in 2020. Net-net, we are on track.

Joseph C. Papa — Chairman of the Board and Chief Executive Officer

On the second part of your question, Umer, on the S1P modulator amiselimod, the trial that we did was an FDA-approved protocol that we had gone and had the FDA approve the protocol. So, we had that in place. We wanted to solve that question or answer that question so that we were assured that there was no Q2 elongation issue. As you know, the cat products in this category have had that problem and we wanted to make sure that that was not going to happen with this product. We had a belief that it wasn’t, but we finished — we wanted to finish the definitive trial for amiselimod to get to that answer. So, that is the reason we did it. There was no request or anything. It was just, we had asked and had that as part of the information that we acquired when we received the product from Mitsubishi on amiselimod. So, I think that answers that part of the question. On the rest of it, we will publish this trial. It has not been published yet, but it will be published and presented in a poster session in the not too distant future. And I think that was the other part of the question.

Okay. Operator, next question please.

Operator

The next question comes from Gregg Gilbert of SunTrust.

Greg Fraser — SunTrust — Analyst

Thank you. It’s Greg Fraser on for Gregg Gilbert. On Xifaxan, can you comment on payer coverage for the IBS indication and whether there is any room for improvement there? And can you also please comment on your initiatives to drive higher growth for the HE indication? Thank you.

Joseph C. Papa — Chairman of the Board and Chief Executive Officer

Sure. We have very strong coverage for Xifaxan. Overall, it’s 98.7%. HE is a little bit stronger, but at that level, it’s essentially universal coverage. I mean, we’ve got very strong coverage on Xifaxan. There is some variation from plan A to plan B, but we’re very pleased with that. On the question of HE, our view is that, we are going to continue to try to improve the compliance and adherence to the product. We have great data that says that if a patient stays compliant with Xifaxan, you can reduce rehospitalization for hepatic encephalopathy and if we’re able to do that, obviously we could save the healthcare system tremendous amount of dollars. So that’s our plan and our focus and we continue to go out and share that data with plan so that they can help lower the cost.

Our fundamental belief though is that as healthcare plans and there’s mergers where the medical and the pharmaceutical comes together, we believe we’re going to have even more traction of that as we look at the opportunity to not only lower the total cost of the patient from the point of view of both the drug cost and the cost of rehospitalization, etc. So, that’s our plan and that’s how we’ve been working on it. We think it’s going to be important for patients going into the future with hepatic encephalopathy, and that — you may recall from our previous comments, we’re even looking at trying to get to some of these patients before the actual hepatic encephalopathy by going after some clinical trial evidence that we see in patients who have psoriasis. So, a lot more work. So, stay tuned to that for the future.

Next question, operator.

Operator

The next question comes from Jason Gerberry of Bank of America.

Jason Gerberry — Bank of America — Analyst

Good morning, thanks for taking my questions. So, quick question on Xifaxan. I think previously in September, you communicated around a 10% to 12% range of growth with minimal contribution from Project CORE. I just wanted to confirm if that’s still the fundamental outlook. And then just on the Significant Seven, is the change in disclosure more or less, hey, this is indicative of our broader pipeline value or is there a diminished outlook as it pertains to the $1 billion target end of 2022? Thanks.

Joseph C. Papa — Chairman of the Board and Chief Executive Officer

Paul, why don’t you take the first part of that?

Paul S. Herendeen — Executive Vice President and Chief Financial Officer

Yeah. Yeah, on the first part of that, I think, what we said was, we kind of continue to believe that Xifaxan would in 2020 versus 2019 that the way — the best way to forecast that would be to think about TRxs growth and use that as a proxy for unit growth and I think we continue to believe that that can be in the high single digits. And to that, you need to add a couple of hundred basis points of net price increase and the reason it’s only a couple hundred basis points is that non-recurring part of the revenue that we saw in 2019 related to the non-durable part of the improvements in gross to nets, some of it is reflected in absolutely improved net selling and step selling price increases that we’ve realized in ’19. But some of it is, it just goes away and becomes kind of a growth headwind. So, net net, I think we pretty much said high single digits units and a couple of hundred basis points of growth. So, circa 10%.

Joseph C. Papa — Chairman of the Board and Chief Executive Officer

On the second part of your question on Significant Seven, the way we look that is, if you go back historically, in 2018, early 2018, we identified seven products that we felt were the key growth drivers for us and as we thought about that, we had great success. This year, it was up 68%, achieved $269 million and expect to see it continue to grow, to be clear going forward. But what we felt is that, that’s going to leave out some really important growth drivers, like Xifaxan, like Trulance, like Thermax, like Biotrue, ULTRA, PreserVision, enVista, Aplenzin and we really came up with a group of not seven, but actually I could be fair, say, so closer to 15 products that are clear drivers for our future.

Now, we’re not going to comment specifically about those, but my point was that, there are some big opportunities there for for the future relative to where we saw the future of this business and specifically you get a product like Xifaxan, our largest product growing double digits, really is a meaningful contributor and you can’t leave that out of the equation as you’re thinking about the future for our business. So, that was really the issue. It was — no concerns about our expectations for the future on that one.

Chris Schott? Next question?

Operator

The next question comes from Chris Schott of JPMorgan. Please go ahead.

Chris Schott — JPMorgan — Analyst

Great, thanks very much. Maybe, first question was — maybe one for Paul, and just following up with the potential for a split and some of those comments you made investor appetite for pure plays. You mentioned that’s a trend to think about down the road, but just maybe a little more color on what you’d need to see to enable a split. Is this simply just a matter of getting leverage to a lower level or is there something fundamentally we need to think about in the businesses before you would consider maybe separating out into individual kind of units as compared to the portfolio you have today.

My second question, which is a quick one on the second Xifaxan filer. Just any color about this filer relative to Sandoz as you think about the defense of that franchise over time? Thanks very much.

Paul S. Herendeen — Executive Vice President and Chief Financial Officer

Yeah, Chris. Thanks for the question. I’ll, obviously take the first one. Yeah, leverage — I would say, our level of leverage today is a — makes it — would make it challenging to pursue something where we spin out one of our entities or whatever. It’s not impossible, but it would make it a fairly significant challenge. That is the primary thing that we’d sit there and say, it becomes more clear for us with the passage of time. And yeah, I don’t think I’m saying anything here that’s groundbreaking. Pure play is a thing. I mean people pure play. We get it. We own businesses that are very attractive and very attractive in their own right, as we’re sitting here today, and for the near term and we continue to believe that we are based on our cap structure stronger together and we’ll continue to evaluate opportunities for providing that pure play as we go forward.

Joseph C. Papa — Chairman of the Board and Chief Executive Officer

On the second part of your question, the new Xifaxan filer, as I mentioned in my comments, that company is Norwich. My understanding, although we don’t have all the information yet, is they filed specifically on both the IBS-D and HE. Our belief is that we have 23 patents. So, when we initially settled with the largest generic company Teva, we had 22 patents. We have now supplemented that with another patent. So, we have 23 patents. So, we feel very strong about our intellectual property position, relative to this filing and we don’t see anything specifically different from this — from what they filed versus what Teva filed. So, we continue to believe we’ve got a strong intellectual property position. So, no other specifics or any differences that we’ve observed.

Operator, I have time for one more question, please.

Operator

The last question comes from Akash Tewari of Wolfe Research.

Akash Tewari — Wolfe Research — Analyst

Hey, guys. Thanks so much. So, look, if we take into account the $275 million LOE impact, the roughly $160 million kind of inventory true-up accrual benefit you had in 2019 that might not necessarily carry over. It looks like you need over $500 million in new product sales year-over-year to kind of hit the midpoint of your guidance on reps. Can you walk us through where that growth is coming from? I’m assuming maybe like a $150 million is on Xifaxan, but what’s the contribution on the Significant Seven, what’s the contribution on Thermage etc., etc. Any color would be really appreciated.

And then, just a bit on the cash flow, there was a bit of dip in Q4. I’d love a bit more color on what happened and then how we should think about it in 2020. It looks like your 2020 cash flow from operations is $1.5 billion, which is a bit lower than what I had expected. So, if there is any color on that, we’d really appreciate it. Thanks.

Joseph C. Papa — Chairman of the Board and Chief Executive Officer

Okay. I’m going to start, but Paul, we’re going to — there is a quite a few questions. We’re going to have to take pieces here. I think the fundamental first question is, where can we grow and how can we grow in 2020 and beyond and what I would simply go back to is that, as we look at our business, we think the overall B&L International business is going to grow at that mid-single-digit rate. I think your characterization of Xifaxan growing ballpark 10%. I think that’s a fair characterization. Solta, I think, you saw the growth that we experienced with Solta in 2019. We clearly think that that’s a great opportunity. And then, the final area I’d say is the derm returning to growth is a really important message. If you think about our business, the B&L business, the Salix business have been important to us, but we’ve had a headwind with dermatology as that dermatology grows, especially, with some of the new programs — new products like Duobrii plus the derm.com — dermatology.com contribution to our business, we think, are all going to be important parts of that growth for the future and obviously we got less LOEs versus we had in the past, but, Paul, anything you want to add to that portion or talk a little bit about cash flow with it.

Paul S. Herendeen — Executive Vice President and Chief Financial Officer

Well, sure. I mean, I actually — I do want to talk about the kind of the growth and where is it going to come from. First is, I think you stated a number of — on the kind of an inventory issue that was we are well above what it really was. In 2019 V ’18, the aggregate amount that it was kind of an one-timer if you will, of us taking those wholesale inventories down, was $76 million. Big number in the quarter, a couple of hundred basis points of volume growth that was based on that relative — basically what was a relative expansion, although was — we are not in expansion at all. And for the year, yeah, it was also baked into our year versus 2018, but not as big a factor on a total revenue base of $8.6 billion odd (Phonetic). If you look at the bridge on Slide 11 of our presentation, that $415 million of increase coming off from what we call base performance is obviously net of any pipeline things that that would have come up. So, that bridge shows you, I think, how we will get to — in the aggregate at a companywide basis, how we’ll get to within our revenue guidance.

With respect to cash flow, I mean, I don’t want to start (Phonetic) with 2019 because as I said on my prepared remarks, we were at $1.501 billion. So just at the low end of our guidance range and to be superclear, that is for cash generated from operations and that’s on a GAAP basis. The primary difference between us — it being $1.5 billion and being $1.55 billion or $1.6 billion was that we did at the end of the year have more inventory than we had perhaps been thinking about when we started the year and that was based on specific decisions that we took to increase inventories of both finished goods and API for key products to ensure that we had consistency of supply. You’ll get our balance sheet later this year. You’ll see the increase in our inventory at the end of the year and that was a primary driver.

Looking ahead to 2020, we have all the factoids that you essentially need to make a — come up with a forecast for cash flow from ops. You got our adjusted EBITDA from the guidance range, you’ve got our interest expense. You’ve got restructuring and other. You’ve got milestones and license agreements. You have a pretty good idea of what our taxes will be based on our guidance there and the one wildcard is working capital. We will grow in 2020 V 2019 and accordingly, that growth if you assume we are currently at the right level of adjusted working capital, which I would comment on in a minute that you would add to working capital. So, you’ll do that math, and you’re going to come out somewhere near $1.5 billion. That’s the way the math works out. I mean the pieces that you can’t see or can’t forecast as well as we can, is the interaction, or the impact of accruals and other things that are very difficult to forecast, but I think the $1.5 billion will be consistent. I mean, interesting if you look at the history, in 2018, it was $1.501 billion and in ’20 — ’19, it was $1.501 billion and we’re guiding to a $1.5 billion in 2020. It’s what we expect today. It could be more than that, but we are — we’ll just have to wait and see how that year plays out.

On my last comment, I said about inventory and working capital. I want to — do provide additional texture. Over time, we are going to drive our inventory balance down. We made some progress and we’ve now taken some strategic steps that have moved us in the opposite direction. Longer term, we will be able to unlock cash from our balance sheet by better managing our inventory balances. We’re not seeing it in 2019 and I am essentially telling you, we’re not going to see it in a significant way in 2020.

Joseph C. Papa — Chairman of the Board and Chief Executive Officer

Stop there. Okay. Let me just thank everyone for joining us and we’ll see you soon as we will be on the road for the next few months at the various healthcare conference. Thank you everyone for joining. Have a great day, everyone.

Operator

(Operator Closing Remarks)

Duration: 64 minutes

Call participants:

Arthur J. Shannon — Senior Vice President and Head of Investor Relations and Communications

Joseph C. Papa — Chairman of the Board and Chief Executive Officer

Paul S. Herendeen — Executive Vice President and Chief Financial Officer

Terence Flynn — Goldman Sachs — Analyst

David Amsellem — Piper Sandler — Analyst

Ken Cacciatore — Cowen & Company — Analyst

Umer Raffat — Evercore — Analyst

Greg Fraser — SunTrust — Analyst

Jason Gerberry — Bank of America — Analyst

Chris Schott — JPMorgan — Analyst

Akash Tewari — Wolfe Research — Analyst

More BHC analysis

All earnings call transcripts

On Oct. 8, Anelise Dao posted a picture to Instagram of herself smiling in the sunshine. She’s wearing a black crop top, and her purple ombré floats to her left shoulder. Intricate black tattoos and long pink nails decorate her fingers, which hold a delicate white rose. At first glance, she could be at Coachella.

But below the smile, the shirt, the nails, and the rose, several large white bandages cover Dao’s stomach. A feeding tube protrudes above her navel. Her bracelets are a mix of dangling silver charms and white hospital bands.

“I am beautiful,” she wrote, “Lines, tubes, scars and all.”

The post, a mashup of the bleak reality of illness and the motivational conventions of Instagram, nails the aesthetic of social media’s latest conquerer: the chronic illness influencer.

Instagram and YouTube accounts dedicated to long-term medical conditions are gaining hundreds of thousands of followers. They share grim, and sometimes glamorous, pictures from the hospital, detailed health confessionals, and words of inspiration.

Instagram users have tagged posts with #chronicillness 2.6 million times. YouTube videos from patients about changing feeding tubes rack up millions of views. Hospital-bed snapshots like Dao’s accrue thousands of likes.

The explosion reflects an increase in chronic illness. The majority of people in the United States—60 percent, according to the U.S. Centers for Disease Control—now suffer from one such sickness, up from 50 percent a decade ago. Just under half the population has been diagnosed with multiple conditions. Ongoing illnesses already account for the majority of health care spending across the globe, and the World Health Organization expects that to grow exponentially in the years to come.

As more people are getting sick, they’re talking about it more often online, especially on Instagram and YouTube. They’re finding community, followings, business opportunities—and skeptics and trolls.

Influencers say the chronic illness community—“spoonies,” as they refer to themselves—has grown massively in the past three years.

“I didn’t know what the term ‘chronic illness’ or ‘invisible illness’ meant before 2016,” said Jameisha Prescod, who runs @youlookokaytome (9,680 followers). In mid-December, she wrote an Instagram post about meeting a fellow lupus sufferer: “Do you remember the first time you spoke to someone else with the same chronic illness as you?… It’s so hard to explain. It’s almost euphoric.”

Kassandra Shore writes about Ehlers-Danlos Syndrome, a group of disorders that produce defects in the body’s connective tissues, at @just.my.genes (4,700 followers). She said she started her Instagram page as a way to update friends and family on her condition last July after a major surgery. Well-meaning relatives couldn’t understand why she would seem fine at a party but need to go to the hospital so often. The fear of publicizing such an intimate journey kept her from opening the account to the public for months. When she did, fellow EDS patients started messaging her, and her following grew.

Shore posted a collage of her most-liked photos from 2019 in late December. All but one showed her in a hospital—standing beside an IV pole, in a hospital bed intubated after surgery, or close to the camera with half a dozen tubes curving into her chest.

Other pages like the Chronic Love Club (@chronicloveclub, 33,600 followers) take submissions from followers and post them to showcase different experiences. Sick Sad Girlz Club (@sicksadgirlz, 7,650 followers), a similar account, featured Lena Dunham talking about her obsessive compulsive disorder, endometriosis, EDS, fibromyalgia, and chronic Lyme in April 2019 (“I have never been well,” she wrote).

At least one person has reported IllnessFakers to Reddit for harassment, but it remains active. Moderators have written into the forum’s rules that they condemn harassment and prohibit posting a target’s personal information, like a home address or a phone number. The forum only allows discussion by pre-approved members, though how someone qualifies is unclear.

“We are NOT here to simply bash spoonies,” moderators wrote. “We are here to call out those who are either overtly faking outright, or exaggerating their problems in such an over-the-top and extreme way that it makes the whole community look bad and silences the voices of those who don’t have the most followers or feel they cannot speak because they don’t have a port or wheelchair or whatever.”

The doubters infuriate advocates for the chronically ill, who say they already struggle to convince their doctors that their symptoms are real. Prescod thinks they are motivated by self-hatred.

“Most of the people who are on (r/IllnessFakers) are people who are sick,” she said. “They’ll say, ‘I have this, and this other person on Instagram definitely doesn’t.’ I think it’s sad. I assumed at first it was people who were well. Everyone presents differently.”

Nevertheless, she and other high-profile spoonies live in dread of being called out on the forum. “I tend to get scared that I’ll be on there one day,” Prescod admitted.

Shore said she actually crafts her Instagram posts with the forum in mind, making sure there’s no room to question whether she’s truly unwell.

“I share just enough to ‘prove’ that this stuff is legitimate. Sharing videos and sharing photos of things as they happen can be helpful. I don’t share my doctors’ names or medication names,” she said. “What’s complicated about chronic illness is that you can be sick one day and be fine in the next couple days.”

In the war between the spoonies and the skeptics, the influencers seem to be winning so far, buoyed by their growing numbers and greater social acceptance of illness—possibly fueled by celebrities talking about their own health struggles with Lyme disease, endometriosis, and autoimmune diseases.

Even corporations are getting in on the action. Nitika Chopra (@nitikachopra, 41,800 followers) has worked with Tide and Dove on sponsored Instagram posts this year. CVS advertised a giveaway on another influencer’s page in August, as did a trendy breathing mask. Some influencers told The Daily Beast they’ll promote the Mighty Pack, a backpack for feeding tubes and other medical equipment, pro bono or in exchange for a pack.

In 2018, Chopra founded Chronicon, a convention for people with chronic illnesses; $150 tickets for the first one, in late October in New York City, sold out three weeks in advance, she said. Panel discussions included topics like “Am I Sick Enough?” and “Chronically Capable of Love” and “The Business of Being You,” which instructed listeners on how to build a following by sharing stories of your chronic illness and monetizing that audience.

“I felt like I was the only person who had psoriasis or psoriatic arthritis, which isn’t true, but every time I met someone else who had it, they felt the same way. Why is that the case?” she told The Daily Beast.

Chopra, a beauty blogger and former talk show host, geared the event towards a younger, Instagram-savvy crowd. The event’s website was awash in millennial pink, as were the name cards emblazoned with the slogan “Breaking the cycle of isolation.” Attendees could partake in hair health consultations and load up their plates under a banner reading “Fight the good fight with good food.”

Speakers’ titles ranged from “board certified OBGYN” to “wellpreneur + teacher.” Former What Not To Wear host Stacy London gave the keynote, calling the event “the community I’ve always hoped for.” A “Chronically Conscious Celebration”—also known as a party—followed. The media company Healthline sponsored the event, and Chopra said Chronicon turned talking about her health into a full-time job.

Ardra Shephard, a blogger and Instagrammer (@MS_trippingonair, 7,000 followers) who writes about her battle with multiple sclerosis, has inked a deal for a show based on her material with the Canadian production studio Shaftesbury, she told The Daily Beast. Since she went public four years ago, blogging and social media have become her livelihood, she said. WebMD made a short film about her, “Tripping On Air: My Trip Through Life With MS”. She also sells merchandise, though she said revenue from it was minimal.

Shephard believes the movement will only grow.

“We don’t see those stories of young people with chronic illness in media,” she said. “We still leave out disability in inclusion. It’s the next big social justice movement.”

Peer-reviewed studies have shown that support groups help chronic illness patients rely less on their doctors and increase their activity levels, and researchers at the National Institute of Health observed that some doctors found social media an effective tool for working with chronic patients on self-management of their own illnesses.

But there’s no guarantee that connecting with fellow sufferers will be good for someone.

The Mayo Clinic warns that patients gathering in support groups may exacerbate each other’s symptoms if they fall prey to “conversations dominated by griping,” “inappropriate or unsound medical advice,” or “competitive comparisons of whose condition or experience is worse.” The online analogue poses similar risks. Writers have described how joining Facebook groups dedicated to chronic illnesses held their focus hostage to the worst possible outcomes that others had suffered.

The American Chronic Pain Association (ACPA) runs support groups across the country. There’s no online component to them at all, said founder and CEO Penney Cowan. “You don’t have the same amount of control in an online group as you do in person,” she told The Daily Beast.

Cowan said talking about physical symptoms during ACPA support group sessions is prohibited in order to redirect participants’ attention to the things they can control and empower them.

Dr. David Stukus, a pediatric allergist with Nationwide Children’s Hospital in Columbus, Ohio, has seen his patients benefit from online communities.

“If you can find others out there that know what it’s like to go through what you’re going through, that’s extremely powerful, and there is a lot of benefit in the emotional support patients get and in tips for daily living that they’re not going to get from your doctor,” he said.

“That said, nobody should be giving out individual specific medical advice online, period,” he cautioned. “Whether you’re a qualified doctor, patient, or anybody else, there are too many important nuances that can influence somebody’s care management that you can’t get from a direct message or a Facebook group.”

Stukus—who corrects false and exaggerated health claims through his Twitter and Instagram accounts—agrees that influencers can hold outsize sway over struggling followers.

“It’s a lot easier to trust somebody who tells an emotional story as opposed to somebody who’s spouting science in a professional way that maybe doesn’t relate to people,” Stukus said. “But somebody’s personal anecdote is really just their own story, and it may have no bearing whatsoever on anybody else in this world.”

Feldman thinks the potential for misinformation is great. That’s why, even though he has never even visited Reddit, he believes a forum like IllnessFakers is a net benefit to society.

“The stuff in real life, the doxxing—that I would have much more trouble with,” he said. “You want to confront the behavior, you don’t want to destroy a person’s life or stalk them. If you do, you want to ask yourself why this has become such a powerful mission.”

But, he added, “it seems like the number of vague ailments that people are reporting is increasing so massively that it’s actually a public service to nip these in the bud.

“Some make no medical sense—after decades of medical intervention, they never get better, and a cause is never found. Yet despite chronic fatigue syndrome, people still manage to fly across the world and give talks and write books. They seem to have enviable energy.”

That kind of comment angers the influencers, who say they are constantly grappling with the tension between appearance and reality. Are they obligated to perform their illnesses? Does looking beautiful in a selfie mean you’re not sick?

“I parked in a handicapped spot two weeks after one of my major spine surgeries, and a woman and her husband yelled at me that I should be ashamed of myself,” Shore said.

“Part of what people like about these Instagram accounts is that they can see someone on a train sitting in handicapped spot, and previously they would have said, ‘Oh, they’re young. They don’t deserve to sit there,’” she added.

“But the more they see of us, the more they understand you can look totally OK on the outside and still have health issues that are very limiting.”

Editor’s note: Ehlers-Danlos Syndrome weakens the body’s connective tissues. A previous version of this story misstated its symptoms. Ardra Shephard has reached a TV deal with Shaftesbury. A previous version of this story misidentified the studio. We regret the errors.

didascalia

Mighty Patch crea adesivi che aspirano tutto il sudiciume dai pori come una calamita, senza rompere la pelle.

fonte

Hero Cosmetics

• Non devi spendere una fortuna per ottenere ottimi prodotti per la cura della pelle che funzionano.
• Ho chiesto al team dello shopping Insider di condividere i loro prodotti per la cura della pelle preferiti di sempre per combattere l'acne – il tutto a meno di $ 25.
• Ancora a caccia? Puoi trovare i nostri 16 marchi di cura della pelle preferiti da acquistare qui.

La cura della pelle può essere un argomento delicato. Ognuno ha preoccupazioni diverse, ma alla fine tutti abbiamo lo stesso obiettivo di sentirci e apparire belli nella nostra pelle.

La verità è che, nonostante tutte le riviste e i siti web ti dicano il contrario, non è necessario spendere centinaia di dollari per la cura della pelle per vedere i risultati. A volte è più semplice (ed economico) davvero meglio.

Ho chiesto ai miei colleghi di condividere i prodotti per la cura della pelle abbordabili che usano e amano, perché chi meglio di ricevere consigli da un gruppo esigente di revisori dei prodotti?

Di seguito troverai 25 prodotti per la cura della pelle a meno di $ 25 che il team di acquisti Insider giura.

Salviette detergenti semplici per il viso

fonte

Amazon

$ 4,46, disponibile su Target e Walmart

Il passo più importante nella prevenzione dell'acne (se almeno me lo chiedi) è rimuovere trucco, sporco e sporcizia dai pori prima di andare a letto. Personalmente trovo che queste salviette per il trucco siano le migliori per il lavoro, ma a volte uso anche l'acqua micellare Simple e un dischetto di cotone riutilizzabile se ho un po 'più di tempo. Le salviette sono semplicemente super convenienti. – Sally Kaplan, senior editor

Lozione tampone Mario Badescu

fonte

Ulta

$ 19, disponibile a Ulta, Sephora e Nordstrom

Per l'acne cistica che si presenta ogni mese, userò questo liquido resistente. È molto acquoso, quindi devo stratificarlo quasi come un siero, ma mi aiuta a liberarmi dai dossi rossi arrabbiati più velocemente e meglio della Lozione Essiccante del marchio; Trovo che la Lozione Essiccante sia migliore per i punti bianchi. – Jada Wong, senior editor

Unguento antibiotico originale di neosporina

fonte

Walmart

$ 6,97, disponibile su Walmart, Target e Amazon

Per i punti bianchi che scelgo (scusate tutti i derm che ho amato prima …), provo a curarlo con un po 'di neosporina. A questo punto, quella whitehead è diventata una lesione aperta, quindi un unguento antibiotico aiuta ad accelerare il processo di guarigione. – Jada Wong, senior editor

Uso questo trucco dal liceo, ed è ancora il mezzo più veloce ed efficace che ho trovato per le imperfezioni di guarigione che ho riscontrato. Accelera il processo, nega totalmente la secchezza, non ostruisce i pori e mi impedisce di toccarli più e di introdurre più germi. – Mara Leighton, giornalista senior

Detergente schiumogeno glicolico Mario Badescu

fonte

Ulta

$ 16, disponibile su Ulta, Sephora e Nordstrom

Non è tanto che ho visto i risultati passare a questo, a parte il fatto che non succede nulla con la mia faccia, nel miglior modo possibile. Quando lo uso non ho alcuna preoccupazione su come apparirà il mio viso. Qualunque cosa sia fatta, è grandiosa. – Breton Fischetti, vicepresidente del commercio

Mighty Patch Hydrocolloid Acne Assorbente Pimple Spot Dot

fonte

Hero Cosmetics

$ 12,50 per 36 patch, disponibili su Amazon

Questa è la mia soluzione ideale per quei brufoli arrabbiati e pieni di pus che spuntano sul tuo viso nei momenti più inopportuni. Gli adesivi assorbono i liquidi cattivi dai brufoli e puoi vedere direttamente i risultati: quando togli l'adesivo il mattino successivo (o anche solo poche ore, a seconda della natura del brufolo), l'adesivo diventa bianco con il pus ha assorbito e il brufolo si è notevolmente sgonfiato.

Dato che sono chiari, li ho persino indossati durante il giorno per lavorare, e nessuno batte un occhio. Sebbene siano più costosi della maggior parte degli altri marchi, ho scoperto che queste particolari patch sono molto più efficaci nel curare il brufolo e hanno anche aderito meglio alla pelle. – Connie Chen, giornalista senior

La mia vita sarebbe stata drasticamente migliore al liceo se questi esistessero allora. Sono incredibili nel ridurre le dimensioni e la gravità delle imperfezioni intense durante la notte – e contrasta la mia tendenza a prenderle, che mantiene le paure di nuovi germi cattivi o di cicatrici a lungo termine fuori dall'equazione. – Mara Leighton, giornalista senior

Detergente viso schiumogeno delicato Cetaphil

fonte

Bersaglio

$ 7,99, disponibili su Target e Ulta

Cetaphil è, letteralmente, l'unica cosa che ho messo in faccia (oltre a SPF, ovviamente). Ho una pelle molto sensibile, così spesso i lavaggi facciali amati contro l'acne mi fanno scoppiare Di Più.

Ho usato il tradizionale detergente per il viso delicato di Cetaphil per anni, ma di recente sono passato al detergente schiumogeno delicato e ho notato immediatamente una differenza. Ho una pelle mista, quindi la mia fronte è grassa e soggetta a sfoghi, mentre il resto del mio viso è costantemente asciutto. La formula in schiuma è il perfetto equilibrio tra la lotta contro l'olio sulla mia fronte senza seccare il resto del viso. La prima volta che ho usato Gentle Foam Cleanser, mi sono svegliato sinceramente scioccato nel vedere una fronte priva di brufoli senza sentirmi stretto e asciutto. Considerando che ho messo in totale due prodotti sul mio viso, sono fiducioso che Cetaphil sia un campione per la pelle sensibile. – Emily Hein, collega della squadra di shopping

Acqua tonificante leggera ad alta umidità Muji

fonte

Muji

$ 21,99, disponibile su Amazon

La mia faccia sembrerebbe un esoscheletro se non fosse per questo toner estremamente idratante. La linea skincare di Muji è l'eroe sconosciuto del marchio, ma scriverei un intero musical su questo prodotto se avessi l'energia creativa. È estremamente idratante, delicato sulla pelle sensibile e funge anche da toner e idratante, particolarmente utile durante l'estate quando si desidera solo uno strato sottile e leggero di prodotto sul viso. – Sally Kaplan, senior editor

Maschera da nuvola in cotone Saturday Skin

fonte

Sephora

$ 6, disponibile da Sephora

Le maschere per il viso sono un modo divertente e conveniente per trattare la tua pelle quando ha bisogno di una piccola spinta. Di recente ho provato questa maschera per il sabato Skin Skin e ha fatto miracoli per la mia pelle jet-lag. Oltre all'adorabile confezione, questa maschera super-idratante è ricca di prebiotici e probiotici per dare alla tua pelle una forte idratazione e luminosità. – Remi Rosmarin, giornalista

Lozione Essiccante Mario Badescu

fonte

Mario Badescu

$ 17, disponibile su Amazon, Ulta e Sephora

La lozione essiccante di Mario Badescu è magica. È un trattamento per l'acne che asciuga i punti bianchi mentre dormi, quindi sono praticamente scomparsi la mattina dopo. Una bottiglia di questa roba mi dura circa sei mesi circa. – Ellen Hoffman, direttore esecutivo

Toner all'acqua di rose Fleur & Bee

fonte

Fleur & Bee

$ 18, disponibile su Amazon

Di recente ho iniziato a utilizzare questo toner di una nuova azienda totalmente vegana perché ero stanco di affrontare la mia acne adulta. Mi piace davvero quanto sia sottile ma dolce il profumo dell'olio di fiori di rosa e che aiuta a gestire la mia pelle grassa durante il giorno. Inoltre, so esattamente cosa mi sto mettendo in faccia. – Francesca Rea, produttrice di contenuti

Differin Adapalene Gel 0,1%

fonte

Amazon

$ 12,88, disponibile su Amazon, Target e Walmart

Differin è un retinoide che, fino a poco tempo fa, per ottenere era necessaria una prescrizione. Il mio dermatologo me lo ha raccomandato come soluzione alternativa per una prescrizione quasi identica che in genere costa $ 233. Da quando lo uso, la consistenza della mia pelle è la migliore che sia mai stata – nessun urto ruvido e irregolare. Mi ha anche aiutato a schiarire la pelle in pochi giorni durante le vacanze. È il mio trattamento topico da banco più affidabile. Puoi trovare una recensione completa qui. – Mara Leighton, giornalista senior

Lozione idratante viso CeraVe PM

fonte

Amazon

da $ 24,76 per due, disponibile su Amazon, Ulta e Target

A volte il meglio è semplice, come nel caso di questa semplice lozione CeraVe. È leggero, ma ancora molto idratante e ha una consistenza morbida come la seta che si sente benissimo sul tuo viso. Come risultato del mio lavoro e di una vera curiosità per la cura della pelle, cerco sempre nuovi prodotti con una gamma di ingredienti diversi. Adoro avere questa lozione come mio controllo; la sua formula semplice può essere stratificata su tutto e so che posso sempre contare su di essa per una pelle costantemente morbida. – Remi Rosmarin, giornalista

Idratante giornaliero Aveeno positivamente radiante SPF 15

fonte

Aveeno

da $ 12,98, disponibile su Amazon e target

Ho usato creme idratanti per farmacie a buon mercato, creme idratanti fantasiose che costano più di quanto sono disposto ad ammettere su Internet e tutto il resto. E devo consegnarlo ad Aveeno; questo è l'unico che ho usato costantemente dal liceo. Sono sempre sorpreso da come pochi di quei fantasiosi idratanti includano SPF, ma questo lo fa e mi sento leggero e mai grasso sulla mia pelle, il che lo rende uno dei miei go-to-go, specialmente in estate. – Ellen Hoffman, direttore esecutivo

Come menziona Ellen, Aveeno merita davvero elogi per questo. Ho provato la mia giusta dose di creme idratanti nella vita (abbastanza per entrare nella terra di Sephora VIB solo al liceo), e mentre ho le mie costose schizzi di lozione, probabilmente non smetterò mai di immagazzinarlo nel mio mobiletto del bagno.

Aggiunge una luminosità visibile, rende la mia pelle notevolmente più morbida e non ha mai ostruito i pori. È un po 'più costoso rispetto alle altre marche di farmacie, ma se hai intenzione di fare acquisti all'estremità più economica dello spettro, questo è il migliore che otterrai. – Mara Leighton, giornalista senior

Tonymoly I am Real Sheet Masks

fonte

Tony Moly

da $ 3, disponibile su Amazon e Ulta

Quando sono andato a Seoul, in Corea, per la prima volta, ero una persona ignorante che non aveva mai usato una maschera per il viso o una maschera per il viso (lo so, lo so, è pazzo!). Prima di partire, ho chiesto ai miei amici cosa avrei dovuto riportare dal mio viaggio, e tutti dicevano la stessa cosa: le maschere in foglio di Tonymoly. Così andai diligentemente nell'affollato quartiere dello shopping di Seoul e vagai per il negozio di cura della pelle dopo il negozio di cura della pelle, carico di campioni gratuiti fino a quando trovai Tonymoly e comprai tre pacchetti.

Ora uso regolarmente queste maschere di Tonymoly (specialmente in inverno) per idratare la pelle. Poiché gli ingredienti sono a base vegetale e delicati, anche queste maschere non irritano la mia pelle. – Malarie Gokey, vicedirettore

Maschera di argilla segreta azteca

fonte

Segreto azteco

$ 7,99, disponibile a Bersaglio e Amazon

Questa maschera di argilla preferita dai cult a buon mercato è una gemma che si nasconde all'aperto. È l'argilla di bentonite al 100%, che succhia olio e sporcizia dai pori come un magnete. E, combinato con aceto di mele, restituisce alla pelle ruvida una consistenza liscia come il bambino. Nel tempo, l'esfoliazione può anche uniformare il tono della pelle. Mi ha portato in un posto dove posso andare comodamente con o senza trucco. Puoi trovare la mia recensione completa qui.

Lo uso da cinque a 10 minuti una o due volte sul viso ogni settimana, o più frequentemente come una striscia di pori fai-da-te per il mio naso. Preferisco usarlo con l'aceto di mele piuttosto che con l'acqua, e sto attento a non lasciarlo mai più a lungo della quantità raccomandata, quindi la mia pelle non inizia a compensare la secchezza producendo più olio. – Mara Leighton, giornalista senior

Brickell Purificante per il viso al carbone purificante per uomo

fonte

Brickell

$ 25, disponibile su Amazon

Ho usato per la prima volta Charcoal Face Wash di Brickell dopo averlo ricevuto in una Birchbox e una volta esaurito il piccolo campione, ne ho rapidamente acquistati altri. Questo è il mio detergente per il viso preferito perché, a differenza della maggior parte dei detergenti economici, non toglie l'umidità. Il carbone fa un ottimo lavoro di pulizia profonda dei miei pori e la miscela di menta piperita e oli di eucalipto dona una sensazione davvero rinfrescante e corroborante. – Amir Ismael, giornalista

Sapone da barra Emu Noble Formula 2% Pyrithione Zinc (ZnP)

fonte

Formula nobile

$ 12,99, disponibile su Amazon e Walmart

Se vuoi che il tuo viso sia perfettamente pulito (non è affatto un'esagerazione) dopo un solo utilizzo, prova questo sapone esfoliante. Ha il 2% di zinco piritione, che ha proprietà antifungine e antibatteriche, quindi chiunque soffra di acne, eczema e dermatite seborroica può trarne beneficio. Altri ingredienti benefici includono olio d'oliva per idratare la pelle, olio di emu per combattere l'infiammazione e il gonfiore e calendula per curare la pelle secca e danneggiata.

Lo uso da più di un mese ed è sempre rassicurante usarlo alla fine della giornata quando voglio davvero ripulire l'olio e lo sporco che si sono accumulati sul mio viso. – Connie Chen, giornalista senior

Devo trovarlo nella frana dei prodotti su Amazon su raccomandazione del mio dermatologo. È l'unica saponetta che ho finito e successivamente sostituita nella memoria recente. È modesto, ma funziona eccezionalmente bene. Lo uso solo per il mio corpo e lo zinco piritione al 2% chiarisce mentre la farina d'avena esfolia, e l'emu e l'olio d'oliva lasciano la pelle idratata anziché spogliata. Per dirla semplicemente, fa esattamente quello che vorresti che facesse. – Mara Leighton, giornalista senior

Siero di acido glicolico puro L´Oreal Paris Revitalift al 10%

fonte

L'Oreal

$ 23,84, disponibile su Amazon

Dopo una combinazione di viaggi, stress e troppi dessert durante le vacanze, ho sperimentato uno dei peggiori breakout che ho avuto negli anni. Ho provato tutti i miei prodotti per la cura della pelle più fantasiosi nel tentativo di chiarirlo, e mentre acceleravano il processo, non hanno fatto nulla per le macchie scure e le cicatrici che erano rimaste indietro. Dopo solo tre giorni di utilizzo di questo siero di acido glicolico, le macchie erano meno evidenti e hanno persino bloccato alcuni brufoli ormonali più recenti che stavano tentando di apparire. Le prime applicazioni pungono un po ', ma per me vale la pena tollerare i risultati. – Ashley Phillips, editrice di stile e bellezza

Idratante viso semplice tipo a pelle con SPF 15

fonte

Walmart

$ 11,54, disponibile su Sephora

Uso l'idratante viso semplice con SPF 15 ogni giorno per proteggere la mia pelle dai raggi del sole. Proprio come qualsiasi altro prodotto Simple, non ha coloranti, profumi o sostanze chimiche strane che possono irritare la pelle. Si assorbe rapidamente nella mia pelle e non si sente mai grassa, il che è importante se sei super biondo come me (alias bianco fantasma o traslucido) e devi assolutamente indossare la protezione solare ogni giorno o rischiare un viso rosa. – Malarie Gokey, vicedirettore

Barra di sapone per l'utilità da uomo di Shea Moisture

fonte

Shea Moisture

$ 3,99, disponibile a destinazione

Con burro di karitè, burro di cacao, burro di mango e avocado, la barra di sapone per l'umidità Shea è perfetta per pulire e aggiungere contemporaneamente l'idratazione necessaria alla mia pelle. Oltre a usarlo per l'umidità quotidiana, può essere usato per lenire le condizioni della pelle come l'eczema e la psoriasi. La parte migliore è che posso usarlo su viso, corpo e capelli. Posso persino insaponarlo come una crema da barba per una rasatura ravvicinata e non secca la pelle. – Amir Ismael, giornalista

troppo cool per la scuola Set di maschere per crema all'uovo

fonte

Amazon

$ 6, disponibile su Ulta

Con tonnellate di benefici idratanti e illuminanti, troppo fresco per la Egg Cream Mask della scuola è uno dei miei modi preferiti per distendermi dopo una lunga giornata e contemporaneamente prendermi cura della mia pelle. La maschera sembra sciocca quando è accesa, ma fa parte del divertimento con queste cose.

Consiglio del professionista: acquista un pacchetto di maschere da cinque fogli su Amazon per $ 24 invece di spendere $ 6 per una singola su Ulta. – Ellen Hoffman, direttore esecutivo

Detergente viso schiumogeno semplice per pelle

fonte

Walmart

$ 5,99, disponibile su Walmart e Amazon

Ho la pelle sensibile, quindi ogni tipo di fragranza mi sconvolge immediatamente e la rende rossa. Sebbene ci siano tonnellate di detergenti naturali per il viso che costano un sacco di soldi, non è necessario acquistarli. Simple rende un eccellente detergente schiumogeno che non ha profumo artificiale, coloranti o sostanze chimiche aggressive. Usa la camomilla, che calma e ammorbidisce la pelle, la glicerina per l'idratazione e il geranio, che lascia la pelle fresca dopo la pulizia.

La sua consistenza delicata e spumosa è perfetta o chiunque abbia la pelle sensibile e non vuole o ha bisogno di esfoliazione ogni giorno. – Malarie Gokey, vicedirettore di Insider Picks

Olio di karitè Tea Tree Oil & Karité Elixir dopobarba per uomo

fonte

Shea Moisture

$ 5,59, disponibile su Amazon

Ho ricevuto questo dopobarba come regalo un paio di anni fa, e ora è l'unico che uso. Non unge perché è un liquido, non una crema, si asciuga molto velocemente e ti dà appena una scossa con gli oli per farti sapere che ha fatto il suo lavoro senza quella sensazione di bruciore che provi da altri prodotti dopobarba. – Breton Fischetti, vicepresidente di Insider Picks

Sapone detergente alle alghe Mario Badescu

fonte

Amazon

$ 14, disponibile su Amazon, Ulta e Sephora

Dopo aver provato la lozione essiccante Mario Badescu, ho deciso di provare questo sapone detergente. Mi piace che non solo pulisca, ma esfolca delicatamente la mia pelle in modo non abrasivo. Odora un po 'come la bassa marea, ma ehi, ciò significa che le proprietà anti-infiammatorie dell'estratto di alga stanno funzionando. – Francesca Rea, produttrice di contenuti

Acqua micellare Bioderma Sensibio H2O

fonte

Dermstore

$ 14,90, disponibile su Amazon, Dermstore e Walmart

Ho provato molte diverse acque micellari, ma questo classico acquisto in farmacia francese è il migliore che abbia mai usato. L'acqua è morbida, rimuove il mascara impermeabile dalle ciglia più delicatamente ed efficacemente degli altri e lascia la pelle pulita e idratata, senza lasciare residui. Per me è stato imbattuto negli ultimi due anni, nonostante la frequente competizione. – Mara Leighton, giornalista senior