Category: Healthcare

U.S. Food and Drug Administration assigned a target action date of May 25, 2021

PRINCETON, N.J. — (BUSINESS WIRE) — $BMY #BMS—Bristol Myers Squibb (NYSE: BMY) today announced that the U.S. Food and Drug Administration (FDA) has accepted its supplemental Biologics License Application (sBLA) for Opdivo^® (nivolumab), in combination with fluoropyrimidine- and platinum-containing chemotherapy, for the treatment of patients with advanced or metastatic gastric cancer, gastroesophageal junction cancer (GEJC) or esophageal adenocarcinoma (EAC), based on results from the CheckMate -649 trial. The FDA granted the application Priority Review and assigned a Prescription Drug User Fee Act (PDUFA) goal date of May 25, 2021.

“Today’s filing acceptance by the FDA marks important progress for the gastrointestinal cancer community and builds on our momentum of advancing immunotherapies to help improve the lives of those with advanced gastric and esophageal tumors,” said Ian M. Waxman, M.D., development lead, gastrointestinal cancers, Bristol Myers Squibb. “The positive results of the CheckMate -649 trial are potentially practice-changing, and we look forward to working with the FDA to possibly bring the first immunotherapy-based treatment option to front-line patients, for whom no novel therapies have been made available in the last decade.”

The filing was based on results from the pivotal Phase 3 CheckMate -649 trial, which showed that first-line treatment with Opdivo plus leucovorin, 5-fluorouracil and oxaliplatin (FOLFOX) or capecitabine and oxaliplatin (CapeOX) led to a statistically significant improvement in overall survival (OS) and progression-free survival (PFS) for patients with unresectable advanced or metastatic gastric cancer, GEJC or EAC whose tumors express PD-L1 with a combined positive score (CPS) ≥ 5, compared to treatment with chemotherapy alone. A statistically significant OS benefit was also observed in the all-randomized population. The safety profile of Opdivo plus chemotherapy was consistent with the known safety profile of the individual treatments. To date, CheckMate -649 is the largest randomized, global Phase 3 study of an immune checkpoint inhibitor-based therapy for patients with gastric cancer, GEJC and EAC.

Bristol Myers Squibb thanks the patients and investigators who were involved in the CheckMate -649 clinical trial.

About CheckMate -649

CheckMate -649 is a Phase 3 randomized, multi-center, open-label study evaluating Opdivo plus chemotherapy or the Opdivo plus Yervoy (ipilimumab) combination compared to chemotherapy alone in patients with previously untreated, non-HER2-positive, advanced or metastatic gastric or GEJ cancer or esophageal adenocarcinoma. The primary endpoints of the trial are OS in PD-L1 positive patients with a combined positive score (CPS) ≥ 5 treated with Opdivo plus chemotherapy and PFS, as assessed by Blinded Independent Central Review (BICR), in CPS ≥ 5 patients treated with Opdivo plus chemotherapy compared to chemotherapy alone. Key secondary endpoints include OS in CPS ≥ 1 and all-randomized patients treated with Opdivo plus chemotherapy as well as OS and time to symptom deterioration (TTSD) in patients treated with Opdivo plus Yervoy compared to chemotherapy alone.

Patients in the Opdivo plus chemotherapy arm received Opdivo 240 mg plus leucovorin, 5-fluorouracil, and oxaliplatin (FOLFOX) every two weeks or Opdivo 360 mg plus capecitabine and oxaliplatin (CapeOX) every three weeks. Patients in the Opdivo plus Yervoy arm received Opdivo 1 mg/kg plus Yervoy 3 mg/kg every three weeks for four cycles followed by Opdivo 240 mg every two weeks. Patients in the chemotherapy arm received FOLFOX or CapeOX every two or three weeks, respectively. All patients continued treatment for up to two years or until disease progression, unacceptable toxicity or withdrawal of consent.

About Gastric Cancer

Gastric cancer, also known as stomach cancer, is the fifth most common cancer and the third leading cause of cancer death worldwide, with over 1,000,000 new cases and approximately 783,000 deaths in 2018. There are several cancers that can be classified as gastric cancer, including certain types of cancers that form in the gastroesophageal junction, the area of the digestive tract where the esophagus and stomach connect. While GEJ cancer has a lower prevalence than distal gastric cancer, it continues to rise. First-line treatment for patients with gastric or GEJ cancer often provides the best chance for efficacy as many patients cannot proceed to subsequent treatments in later settings due to deterioration.

About Esophageal Cancer

Esophageal cancer is the seventh most common cancer and the sixth leading cause of death from cancer worldwide, with approximately 572,000 new cases and over 508,000 deaths in 2018. The two most common types of esophageal cancer are squamous cell carcinoma and adenocarcinoma, which account for approximately 85% and 14% of all esophageal cancers, respectively, though esophageal tumor histology can vary by region with the highest rate of esophageal adenocarcinoma occurring in North America (65%). 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: Creating a Better Future for People with Cancer

Bristol Myers Squibb is inspired by a single vision — transforming people’s lives through science. The goal of the company’s cancer research is to deliver medicines that offer each patient a better, healthier life and to make cure a possibility. Building on a legacy across a broad range of cancers that have changed survival expectations for many, Bristol Myers Squibb researchers are exploring new frontiers in personalized medicine, and through innovative digital platforms, are turning data into insights that sharpen their focus. Deep scientific expertise, cutting-edge capabilities and discovery platforms enable the company to look at cancer from every angle. Cancer can have a relentless grasp on many parts of a patient’s life, and Bristol Myers Squibb is committed to taking actions to address all aspects of care, from diagnosis to survivorship. Because as a leader in cancer care, Bristol Myers Squibb is working to empower all people with cancer to have a better future.

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.

INDICATIONS

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), in combination with YERVOY^® (ipilimumab), is indicated for the first-line treatment of adult patients with metastatic non-small cell lung cancer (NSCLC) whose tumors express PD-L1 (≥1%) as determined by an FDA-approved test, with no EGFR or ALK genomic tumor aberrations.

OPDIVO^® (nivolumab), in combination with YERVOY^® (ipilimumab) and 2 cycles of platinum-doublet chemotherapy, is indicated for the first-line treatment of adult patients with metastatic or recurrent non-small cell lung cancer (NSCLC), with no EGFR or ALK genomic tumor aberrations.

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), in combination with YERVOY^® (ipilimumab), is indicated for the first-line treatment of adult patients with unresectable malignant pleural mesothelioma (MPM).

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 overall response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials.

OPDIVO^® (nivolumab), in combination with YERVOY^® (ipilimumab), 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 overall response rate and duration 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.

OPDIVO^® (nivolumab) is indicated for the treatment of patients with unresectable advanced, recurrent or metastatic esophageal squamous cell carcinoma (ESCC) after prior fluoropyrimidine- and platinum-based chemotherapy.

IMPORTANT SAFETY INFORMATION

Severe and Fatal Immune-Mediated Adverse Reactions

Immune-mediated adverse reactions listed herein may not include all possible severe and fatal immune-mediated adverse reactions.

Immune-mediated adverse reactions, which may be severe or fatal, can occur in any organ system or tissue. While immune-mediated adverse reactions usually manifest during treatment, they can also occur after discontinuation of OPDIVO or YERVOY. Early identification and management are essential to ensure safe use of OPDIVO and YERVOY. Monitor for signs and symptoms that may be clinical manifestations of underlying immune-mediated adverse reactions. Evaluate clinical chemistries including liver enzymes, creatinine, adrenocorticotropic hormone (ACTH) level, and thyroid function at baseline and periodically during treatment with OPDIVO and before each dose of YERVOY. In cases of suspected immune-mediated adverse reactions, initiate appropriate workup to exclude alternative etiologies, including infection. Institute medical management promptly, including specialty consultation as appropriate.

Withhold or permanently discontinue OPDIVO and YERVOY depending on severity (please see section 2 Dosage and Administration in the accompanying Full Prescribing Information). In general, if OPDIVO or YERVOY interruption or discontinuation is required, administer systemic corticosteroid therapy (1 to 2 mg/kg/day prednisone or equivalent) until improvement to Grade 1 or less. Upon improvement to Grade 1 or less, initiate corticosteroid taper and continue to taper over at least 1 month. Consider administration of other systemic immunosuppressants in patients whose immune-mediated adverse reactions are not controlled with corticosteroid therapy. Toxicity management guidelines for adverse reactions that do not necessarily require systemic steroids (e.g., endocrinopathies and dermatologic reactions) are discussed below.

Immune-Mediated Pneumonitis

OPDIVO and YERVOY can cause immune-mediated pneumonitis. The incidence of pneumonitis is higher in patients who have received prior thoracic radiation. In patients receiving OPDIVO monotherapy, immune-mediated pneumonitis occurred in 3.1% (61/1994) of patients, including Grade 4 (<0.1%), Grade 3 (0.9%), and Grade 2 (2.1%). In HCC patients receiving OPDIVO 1 mg/kg with YERVOY 3 mg/kg every 3 weeks, immune-mediated pneumonitis occurred in 10% (5/49) of patients. In patients receiving OPDIVO 3 mg/kg with YERVOY 1 mg/kg every 3 weeks, immune-mediated pneumonitis occurred in 3.9% (26/666) of patients, including Grade 3 (1.4%) and Grade 2 (2.6%). In NSCLC patients receiving OPDIVO 3 mg/kg every 2 weeks with YERVOY 1 mg/kg every 6 weeks, immune-mediated pneumonitis occurred in 9% (50/576) of patients, including Grade 4 (0.5%), Grade 3 (3.5%), and Grade 2 (4.0%). Four patients (0.7%) died due to pneumonitis.

Immune-Mediated Colitis

OPDIVO and YERVOY can cause immune-mediated colitis, which may be fatal. A common symptom included in the definition of colitis was diarrhea. 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. In patients receiving OPDIVO monotherapy, immune-mediated colitis occurred in 2.9% (58/1994) of patients, including Grade 3 (1.7%) and Grade 2 (1%). In patients receiving OPDIVO 1 mg/kg with YERVOY 3 mg/kg every 3 weeks, immune-mediated colitis occurred in 25% (115/456) of patients, including Grade 4 (0.4%), Grade 3 (14%) and Grade 2 (8%). In patients receiving OPDIVO 3 mg/kg with YERVOY 1 mg/kg every 3 weeks, immune-mediated colitis occurred in 9% (60/666) of patients, including Grade 3 (4.4%) and Grade 2 (3.7%).

In a separate Phase 3 trial of YERVOY 3 mg/kg monotherapy, immune-mediated colitis occurred in 12% (62/511) of patients, including Grade 3-5 (7%) and Grade 2 (5%).

Immune-Mediated Hepatitis

OPDIVO and YERVOY can cause immune-mediated hepatitis. In patients receiving OPDIVO monotherapy, immune-mediated hepatitis occurred in 1.8% (35/1994) of patients, including Grade 4 (0.2%), Grade 3 (1.3%), and Grade 2 (0.4%). In patients receiving OPDIVO 1 mg/ kg with YERVOY 3 mg/kg every 3 weeks, immune-mediated hepatitis occurred in 15% (70/456) of patients, including Grade 4 (2.4%), Grade 3 (11%), and Grade 2 (1.8%). In patients receiving OPDIVO 3 mg/kg with YERVOY 1 mg/kg every 3 weeks, immune-mediated hepatitis occurred in 7% (48/666) of patients, including Grade 4 (1.2%), Grade 3 (4.9%), and Grade 2 (0.4%).

In a separate Phase 3 trial of YERVOY 3 mg/kg monotherapy, immune-mediated hepatitis occurred in 4.1% (21/511) of patients, including Grade 3-5 (1.6%) and Grade 2 (2.5%).

Immune-Mediated Endocrinopathies

OPDIVO and YERVOY can cause primary or secondary adrenal insufficiency, immune-mediated hypophysitis, immune-mediated thyroid disorders, and Type 1 diabetes mellitus, which can present with diabetic ketoacidosis. Withhold OPDIVO and YERVOY depending on severity (please see section 2 Dosage and Administration in the accompanying Full Prescribing Information). For Grade 2 or higher adrenal insufficiency, initiate symptomatic treatment, including hormone replacement as clinically indicated. Hypophysitis can present with acute symptoms associated with mass effect such as headache, photophobia, or visual field defects. Hypophysitis can cause hypopituitarism; initiate hormone replacement as clinically indicated. Thyroiditis can present with or without endocrinopathy. Hypothyroidism can follow hyperthyroidism; initiate hormone replacement or medical management as clinically indicated. Monitor patients for hyperglycemia or other signs and symptoms of diabetes; initiate treatment with insulin as clinically indicated.

In patients receiving OPDIVO monotherapy, adrenal insufficiency occurred in 1% (20/1994), including Grade 3 (0.4%) and Grade 2 (0.6%). In patients receiving OPDIVO 1 mg/kg with YERVOY 3 mg/kg every 3 weeks, adrenal insufficiency occurred in 8% (35/456), including Grade 4 (0.2%), Grade 3 (2.4%), and Grade 2 (4.2%). In patients receiving OPDIVO 3 mg/kg with YERVOY 1 mg/kg every 3 weeks, adrenal insufficiency occurred in 7% (48/666) of patients, including Grade 4 (0.3%), Grade 3 (2.5%), and Grade 2 (4.1%).

In patients receiving OPDIVO monotherapy, hypophysitis occurred in 0.6% (12/1994) of patients, including Grade 3 (0.2%) and Grade 2 (0.3%). In patients receiving OPDIVO 1 mg/kg with YERVOY 3 mg/kg every 3 weeks, hypophysitis occurred in 9% (42/456), including Grade 3 (2.4%) and Grade 2 (6%). In patients receiving OPDIVO 3 mg/kg with YERVOY 1 mg/kg every 3 weeks, hypophysitis occurred in 4.4% (29/666) of patients, including Grade 4 (0.3%), Grade 3 (2.4%), and Grade 2 (0.9%).

In patients receiving OPDIVO monotherapy, thyroiditis occurred in 0.6% (12/1994) of patients, including Grade 2 (0.2%). In patients receiving OPDIVO 3 mg/kg with YERVOY 1 mg/kg every 3 weeks, thyroiditis occurred in 2.7% (22/666) of patients, including Grade 3 (4.5%) and Grade 2 (2.2%).

In patients receiving OPDIVO monotherapy, hyperthyroidism occurred in 2.7% (54/1994) of patients, including Grade 3 (<0.1%) and Grade 2 (1.2%). In patients receiving OPDIVO 1 mg/kg with YERVOY 3 mg/kg every 3 weeks, hyperthyroidism occurred in 9% (42/456) of patients, including Grade 3, (0.9%) and Grade 2 (4.2%). In patients receiving OPDIVO 3 mg/kg with YERVOY 1 mg/kg every 3 weeks, hyperthyroidism occurred in 12% (80/666) of patients, including Grade 3 (0.6%), and Grade 2 (4.5%).

In patients receiving OPDIVO monotherapy, hypothyroidism occurred in 8% (163/1994) of patients, including Grade 3 (0.2%) and Grade 2 (4.8%). In patients receiving OPDIVO 1 mg/kg with YERVOY 3 mg/kg every 3 weeks, hypothyroidism occurred in 20% (91/456) of patients, including Grade 3 (0.4%) and Grade 2 (11%). In patients receiving OPDIVO 3 mg/kg with YERVOY 1 mg/kg every 3 weeks, hypothyroidism occurred in 18% (122/666) of patients, including Grade 3 (0.6%) and Grade 2 (11%).

In patients receiving OPDIVO monotherapy, diabetes occurred in 0.9% (17/1994) of patients, including Grade 3 (0.4%) and Grade 2 (0.3%), and 2 cases of diabetic ketoacidosis. In patients receiving OPDIVO 3 mg/kg with YERVOY 1 mg/kg every 3 weeks, diabetes occurred in 2.7% (15/666) of patients, including Grade 4 (0.6%), Grade 3 (0.3%), and Grade 2 (0.9%).

In a separate Phase 3 trial of YERVOY 3 mg/kg monotherapy, Grade 2-5 immune-mediated endocrinopathies occurred in 4% (21/511) of patients. Severe to life-threatening (Grade 3-4) endocrinopathies 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. Moderate (Grade 2) endocrinopathy occurred in 12 patients (2.3%), including hypothyroidism, adrenal insufficiency, hypopituitarism, hyperthyroidism and Cushing’s syndrome.

Immune-Mediated Nephritis with Renal Dysfunction

OPDIVO and YERVOY can cause immune-mediated nephritis. In patients receiving OPDIVO monotherapy, immune-mediated nephritis and renal dysfunction occurred in 1.2% (23/1994) of patients, including Grade 4 (<0.1%), Grade 3 (0.5%), and Grade 2 (0.6%). In patients receiving OPDIVO 3 mg/kg with YERVOY 1 mg/kg every 3 weeks, immune-mediated nephritis with renal dysfunction occurred in 4.1% (27/666) of patients, including Grade 4 (0.6%), Grade 3 (1.1%), and Grade 2 (2.2%).

Immune-Mediated Dermatologic Adverse Reactions

OPDIVO can cause immune-mediated rash or dermatitis. Exfoliative dermatitis, including Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), and drug rash with eosinophilia and systemic symptoms (DRESS) has occurred with PD-1/PD-L1 blocking antibodies.

Contacts

Bristol Myers Squibb

Media Inquiries:
Media@BMS.com

Investors:
Tim Power

609-252-7509

timothy.power@bms.com

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Two-Day Special Event Will Showcase The Latest Innovations in Eye Care

OAKLAND, N.J.–(BUSINESS WIRE)–#RDx–Topcon Healthcare, a leading provider of medical devices and software solutions for the global eye care community, announced today that it will host a two-day virtual symposia and expo entitled eyeRISE on February 9-10, 2021.

eyeRISE, or Eye Research Innovation Symposia & Expo, is a new, multi-disciplinary virtual congress showcasing the latest innovations in eye care. It will feature three solutions-focused tracks, delivering clinical and practical education through symposia, roundtable discussions and interactive workshops.

The two-day special event will feature more than three dozen globally-renowned speakers representing 17 countries and a range of specialties. Educational tracks are Building Clinical Confidence which includes topics focused on retina, glaucoma and imaging; Entering New Markets which addresses the barriers to entering myopia and dry eye management; and Too Many Patients, Not Enough Time highlighting topics such as ocular telehealth and remote diagnostics.

“We are very excited to announce eyeRISE, a one-of-a-kind, ground-breaking event that will bring together some of the most recognized names in the eye care industry to discuss the latest research and trends in patient care and practice management. In the absence of live meetings, eyeRISE provides an engaging, interactive virtual platform and offers education for a wide range of disciplines. It features solution-focused tracks for real world clinical and business management applications. eyeRISE is the culmination of Topcon’s unwavering commitment to support continued innovation in eye care,” stated Carolyn Evangelista, Global Director of Medical Affairs for Topcon Healthcare.

“eyeRISE will build on the success of our previous ISSOCT conferences and expand to include all facets of eye care, delivering clinical education for the retina, glaucoma and anterior segment subspecialties. The esteemed lecture panel will present their clinical findings on the latest research topics and innovation in eye care. It should prove to be a highly informative and enlightening meeting for all attendees,” stated ISSOCT Chairman Richard F. Spaide, MD, of Vitreous Retina Macula Consultants of New York, United States.

“Having the opportunity to network with colleagues and learn about the latest trends and technologies in eye care is critical for today’s practitioners, particularly in light of the global pandemic. eyeRISE provides practitioners with a unique opportunity to interact with the faculty and each other and gain practical tips and clinical insights. Given the challenges facing today’s eye care practitioners, eyeRISE represents a wonderful learning opportunity for all clinicians,” summarized faculty member Mingguang He, MD, PhD, Professor at the University of Melbourne, Australia.

For more information on eyeRISE or to register for the event, please visit Eyerise2021.com.

About Topcon Healthcare

Topcon Healthcare sees eye health differently. Our vision is to empower providers with smart and efficient technologies for enhanced patient care. Keeping pace with the ever-changing landscape of the healthcare industry, we offer the latest integrated solutions including advanced multi-modal imaging, vendor-neutral data management, safe distancing and ground-breaking remote diagnostic technology.

A globally oriented business, Topcon is focused on developing solutions towards solving societal challenges in the mega-domains of healthcare, agriculture, and infrastructure. In healthcare, these challenges include increasing eye disease, rising medical costs, access to healthcare and physician shortages. By investing in value-driven innovations, Topcon works to enable people to enjoy good health and a high quality of life.

Contacts

Christina Kirby

Director, Product Marketing Americas

Topcon Healthcare

E-mail: ckirby@topcon.com

• First HER2 directed medicine approved for patients with gastric cancer in a decade

TOKYO & MUNICH & BASKING RIDGE, N.J.–(BUSINESS WIRE)–Daiichi Sankyo Company, Limited (hereafter, Daiichi Sankyo) and AstraZeneca’s ENHERTU^® (fam-trastuzumab deruxtecan-nxki) has been approved in the U.S. for the treatment of adult patients with locally advanced or metastatic HER2 positive gastric or gastroesophageal junction (GEJ) adenocarcinoma who have received a prior trastuzumab-based regimen.

In the U.S., gastric cancer is more frequently diagnosed in the advanced stage, with only approximately 5% of patients surviving five years.^1,2 Approximately one in five gastric cancers are HER2 positive.³

“Patients with metastatic HER2 positive gastric cancer with progression following first-line treatment have historically faced poor outcomes, including low response to treatment and rapid disease progression,” said Ronan Kelly, MD, MBA, Director of the Charles A. Sammons Cancer Center and the W.W. Caruth, Jr. Chair of Immunology at Baylor University Medical Center, Dallas, Texas. “This approval represents the first time a HER2 directed medicine has demonstrated a significant improvement in survival compared to chemotherapy for patients following initial treatment in the metastatic setting and it has the potential to become the new standard of care for this patient population.”

Regular approval by the U.S. Food and Drug Administration (FDA) was based on the positive results from the randomized pivotal DESTINY-Gastric01 phase 2 trial, in which ENHERTU demonstrated a statistically significant and clinically meaningful improvement in overall survival (OS) and objective response rate (ORR) versus chemotherapy (irinotecan or paclitaxel) in patients with advanced gastric or GEJ adenocarcinoma who had progressed on at least two prior regimens including trastuzumab, a fluoropyrimidine and a platinum-containing chemotherapy. ENHERTU is approved with Boxed WARNINGS for interstitial lung disease (ILD)/pneumonitis and embryo-fetal toxicity.

In the DESTINY-Gastric01 trial, patients (n=126) in the ENHERTU treatment arm had a 41% reduction in the risk of death versus patients (n=62) treated with chemotherapy (based on a hazard ratio [HR] of 0.59; 95% confidence interval [CI] 0.39-0.88; p=0.0097) at a pre-specified interim analysis with a median OS of 12.5 months [95% CI 9.6-14.3] versus 8.4 months [95% CI 6.9-10.7] with chemotherapy.

Confirmed ORR, assessed by independent central review, was a major efficacy outcome. Results showed a confirmed ORR of 40.5% [95% CI 31.8-49.6] with ENHERTU compared to 11.3% [95% CI 4.7-21.9] with chemotherapy. Patients treated with ENHERTU had a 7.9% complete response rate (n=10) and a 32.5% partial response rate (n=41) compared to a complete response rate of 0% (n=0) and a partial response rate of 11.3% (n=7) for patients treated with chemotherapy. Additionally, ENHERTU showed a median duration of response (DoR) of 11.3 months [95% CI 5.6-NR] versus 3.9 months [95% CI 3.0-4.9] with chemotherapy.

ENHERTU also demonstrated a median progression-free survival (PFS) of 5.6 months [95% CI 4.3-6.9] compared to 3.5 months [95% CI 2.0-4.3] (HR=0.47; 95% CI 0.31-0.71) with chemotherapy.

Results from the DESTINY-Gastric01 trial were presented at the 2020 American Society of Clinical Oncology (ASCO) meeting and published in The New England Journal of Medicine.⁴

ENHERTU is approved with Boxed WARNINGS for interstitial lung disease (ILD)/pneumonitis and embryo-fetal toxicity. The safety of ENHERTU was evaluated in 187 patients with locally advanced or metastatic HER2 positive gastric or GEJ adenocarcinoma in DESTINY-Gastric01. The most common adverse reactions (≥20%), including laboratory abnormalities, were hemoglobin decreased, white blood cell count decreased, neutrophil count decreased, lymphocyte count decreased, platelet count decreased, nausea, decreased appetite, anemia, aspartate aminotransferase increased, fatigue, blood alkaline phosphatase increased, alanine aminotransferase increased, diarrhea, hypokalemia, vomiting, constipation, blood bilirubin increased, pyrexia, and alopecia. In DESTINY-Gastric01, of the 125 patients with locally advanced or metastatic HER2 positive gastric or GEJ adenocarcinoma treated with ENHERTU 6.4 mg/kg, interstitial lung disease occurred in 10% of patients. Median time to first onset of ILD was 2.8 months (range: 1.2 to 21.0).

“ENHERTU is the first antibody drug conjugate to receive approval in the U.S. for the treatment of patients with metastatic gastric cancer, and represents a major advance in managing this difficult-to-treat disease,” said Antoine Yver, MD, MSc, Executive Vice President and Global Head, Oncology Research and Development, Daiichi Sankyo. “This second indication in the U.S. represents an important step forward in our ambitious plan to accelerate the development of ENHERTU across a broad range of HER2 targetable cancers.”

“Today’s approval of ENHERTU represents the first HER2 directed medicine approved in a decade for patients with HER2 positive metastatic gastric cancer,” said Dave Fredrickson, Executive Vice President, Oncology Business Unit, AstraZeneca. “The results from the DESTINY-Gastric01 trial highlight the potential to change clinical practice, showing a forty-one percent improvement in survival and a response rate more than three times higher with ENHERTU compared to chemotherapy. We are thrilled to bring this important medicine to more patients and physicians in the U.S.”

This is the second regulatory approval for ENHERTU in the U.S. ENHERTU is also approved in the U.S. under accelerated approval, and in Japan, under the conditional early approval system, for the treatment of adult patients with unresectable or metastatic HER2 positive breast cancer who have received two or more prior anti-HER2-based regimens in the metastatic setting based on the DESTINY-Breast01 trial. ENHERTU is also approved in Japan for HER2 positive unresectable advanced or recurrent gastric cancer that has progressed after chemotherapy based on the DESTINY-Gastric01 trial.

ENHERTU previously received Priority Review and Breakthrough Therapy Designation (BTD) in the U.S. for the treatment of patients with previously treated HER2 positive metastatic gastric cancer, as well as Orphan Drug Designation (ODD) for patients with gastric cancer, including gastroesophageal junction cancer. Two additional phase 2 trials, DESTINY-Gastric02 and DESTINY-Gastric03, are underway, further evaluating the use of ENHERTU in patients with HER2 positive metastatic gastric cancer.

Daiichi Sankyo and AstraZeneca are committed to ensuring that patients in the U.S. who are prescribed ENHERTU can access the medication and receive necessary financial support. Provider and patient support, reimbursement and distribution for ENHERTU in the U.S. will be accessible by visiting www.ENHERTU4U.com or calling 1-833-ENHERTU (1-833-364-3788).

Please visit www.ENHERTU.com for full Prescribing Information, including Boxed WARNINGS, and Medication Guide.

About Gastric Cancer

Gastric (stomach) cancer is the fifth most common cancer worldwide and the third leading cause of cancer mortality with a five-year survival rate of 5% for metastatic disease; there were approximately one million new cases reported in 2020 and more than 768,000 deaths.^2,5 In the U.S., it is estimated that 27,600 new cases of gastric cancer were diagnosed in 2020 and more than 11,000 people died from the disease.⁶

Approximately one in five gastric cancers are HER2 positive.³ HER2 is a tyrosine kinase receptor growth-promoting protein expressed on the surface of many types of tumors including breast, gastric, lung and colorectal cancer. Gastric cancer is usually diagnosed in the advanced stage, but even when diagnosed in earlier stages of the disease, the survival rate remains modest.¹ Recommended first-line treatment for HER2 positive advanced or metastatic gastric cancer is combination chemotherapy plus trastuzumab, an anti-HER2 medicine, which has been shown to improve survival outcomes when added to chemotherapy. For patients with metastatic gastric cancer that progresses following initial treatment with a trastuzumab-based regimen, there were previously no other approved HER2 targeted medicines prior to the approval of ENHERTU.³

About DESTINY-Gastric01

DESTINY-Gastric01 is an open-label, multi-center, randomized, pivotal phase 2 trial evaluating the safety and efficacy of ENHERTU (6.4 mg/kg) versus investigator’s choice of chemotherapy in a primary cohort of 188 patients from Japan and South Korea with HER2 positive (defined as IHC3+ or IHC2+/ISH+), advanced gastric or GEJ adenocarcinoma who had progressed on two or more prior treatment regimens including trastuzumab, a fluoropyrimidine and platinum-containing chemotherapy. Patients were randomized 2:1 to receive ENHERTU or investigator’s choice of chemotherapy (paclitaxel or irinotecan monotherapy). Patients were treated with ENHERTU 6.4mg/kg once every three weeks or chemotherapy.

The main efficacy outcome measures were ORR assessed by independent central review according to RECIST v1.1 and OS in the intent-to-treat population. Additional efficacy outcome measures were PFS and DoR.

About ENHERTU

ENHERTU^® (trastuzumab deruxtecan; fam-trastuzumab deruxtecan-nxki in the U.S.) is a HER2 directed antibody drug conjugate (ADC). Designed using Daiichi Sankyo’s proprietary DXd ADC technology, ENHERTU is the lead ADC in the oncology portfolio of Daiichi Sankyo and the most advanced program in AstraZeneca’s ADC scientific platform.

ADCs are targeted cancer medicines that deliver cytotoxic chemotherapy (“payload”) to cancer cells via a linker attached to a monoclonal antibody that binds to a specific target expressed on cancer cells. ENHERTU is comprised of a humanized anti-HER2 IgG1 monoclonal antibody with the same amino acid sequence as trastuzumab attached to a topoisomerase I inhibitor payload, an exatecan derivative, via a tetrapeptide-based cleavable linker.

ENHERTU (5.4 mg/kg) is approved in the U.S. under accelerated approval, and in Japan, under the conditional early approval system, for the treatment of adult patients with unresectable or metastatic HER2 positive breast cancer who have received two or more prior anti-HER2-based regimens in the metastatic setting based on the DESTINY-Breast01 trial, and received a CHMP positive opinion in December 2020 as monotherapy for the treatment of adult patients with unresectable or metastatic HER2 positive breast cancer who have received two or more prior anti-HER2 based regimens. ENHERTU (6.4 mg/kg) is also approved in the U.S. and Japan for the treatment of previously treated patients with HER2 positive metastatic gastric cancer based on the DESTINY-Gastric01 trial.

About the ENHERTU Clinical Development Program

A comprehensive development program is underway globally with nine pivotal trials evaluating the efficacy and safety of ENHERTU monotherapy across multiple HER2 targetable cancers including breast, gastric and lung cancers. Trials in combination with other anticancer treatments, such as immunotherapy, are also underway.

In May 2020, ENHERTU received BTD in the U.S. for the treatment of patients with metastatic non-small cell lung cancer whose tumors have a HER2 mutation and with disease progression on or after platinum-based therapy.

In March 2020, the European Medicines Agency’s CHMP granted ENHERTU accelerated assessment for the treatment of adults with unresectable or metastatic HER2 positive breast cancer who have received two or more prior anti-HER2 based regimens.

About the Collaboration between Daiichi Sankyo and AstraZeneca

Daiichi Sankyo and AstraZeneca entered into a global collaboration to jointly develop and commercialize ENHERTU (a HER2 directed ADC) in March 2019, and datopotamab deruxtecan (Dato-DXd; DS-1062; a TROP2 directed ADC) in July 2020, except in Japan where Daiichi Sankyo maintains exclusive rights. Daiichi Sankyo is responsible for manufacturing and supply of ENHERTU and datopotamab deruxtecan.

U.S. Important Safety Information for ENHERTU

Indications

ENHERTU is a HER2-directed antibody and topoisomerase inhibitor conjugate indicated for the treatment of adult patients with:

• Unresectable or metastatic HER2-positive breast cancer who have received two or more prior anti-HER2-based regimens in the metastatic setting.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 a confirmatory trial.

• Locally advanced or metastatic HER2-positive gastric or gastroesophageal junction adenocarcinoma who have received a prior trastuzumab-based regimen.

WARNING: INTERSTITIAL LUNG DISEASE and EMBRYO-FETAL TOXICITY Interstitial lung disease (ILD) and pneumonitis, including fatal cases, have been reported with ENHERTU. Monitor for and promptly investigate signs and symptoms including cough, dyspnea, fever, and other new or worsening respiratory symptoms. Permanently discontinue ENHERTU in all patients with Grade 2 or higher ILD/pneumonitis. Advise patients of the risk and to immediately report symptoms. Exposure to ENHERTU during pregnancy can cause embryo-fetal harm. Advise patients of these risks and the need for effective contraception.

Contraindications

None.

Warnings and Precautions

Interstitial Lung Disease / Pneumonitis

Severe, life-threatening, or fatal interstitial lung disease (ILD), including pneumonitis, can occur in patients treated with ENHERTU. Advise patients to immediately report cough, dyspnea, fever, and/or any new or worsening respiratory symptoms. Monitor patients for signs and symptoms of ILD. Promptly investigate evidence of ILD. Evaluate patients with suspected ILD by radiographic imaging. Consider consultation with a pulmonologist. For asymptomatic ILD/pneumonitis (Grade 1), interrupt ENHERTU until resolved to Grade 0, then if resolved in ≤28 days from date of onset, maintain dose. If resolved in >28 days from date of onset, reduce dose one level. Consider corticosteroid treatment as soon as ILD/pneumonitis is suspected (e.g., ≥0.5 mg/kg/day prednisolone or equivalent). For symptomatic ILD/pneumonitis (Grade 2 or greater), permanently discontinue ENHERTU. Promptly initiate systemic corticosteroid treatment as soon as ILD/pneumonitis is suspected (e.g., ≥1 mg/kg/day prednisolone or equivalent) and continue for at least 14 days followed by gradual taper for at least 4 weeks.

Metastatic Breast Cancer

In clinical studies, of the 234 patients with unresectable or metastatic HER2-positive breast cancer treated with ENHERTU 5.4 mg/kg, ILD occurred in 9% of patients. Fatal outcomes due to ILD and/or pneumonitis occurred in 2.6% of patients treated with ENHERTU. Median time to first onset was 4.1 months (range: 1.2 to 8.3).

Locally Advanced or Metastatic Gastric Cancer

In DESTINY-Gastric01, of the 125 patients with locally advanced or metastatic HER2-positive gastric or GEJ adenocarcinoma treated with ENHERTU 6.4 mg/kg, ILD occurred in 10% of patients. Median time to first onset was 2.8 months (range: 1.2 to 21.0).

Neutropenia

Severe neutropenia, including febrile neutropenia, can occur in patients treated with ENHERTU. Monitor complete blood counts prior to initiation of ENHERTU and prior to each dose, and as clinically indicated. For Grade 3 neutropenia (Absolute Neutrophil Count [ANC] <1.0 to 0.5 x 10⁹/L) interrupt ENHERTU until resolved to Grade 2 or less, then maintain dose. For Grade 4 neutropenia (ANC <0.5 x 10⁹/L) interrupt ENHERTU until resolved to Grade 2 or less. Reduce dose by one level. For febrile neutropenia (ANC <1.0 x 10⁹/L and temperature >38.3ºC or a sustained temperature of ≥38ºC for more than 1 hour), interrupt ENHERTU until resolved. Reduce dose by one level.

Metastatic Breast Cancer

In clinical studies, of the 234 patients with unresectable or metastatic HER2-positive breast cancer who received ENHERTU 5.4mg/kg, a decrease in neutrophil count was reported in 62% of patients. Sixteen percent had Grade 3 or 4 decrease in neutrophil count. Median time to first onset of decreased neutrophil count was 23 days (range: 6 to 547). Febrile neutropenia was reported in 1.7% of patients.

Locally Advanced or Metastatic Gastric Cancer

In DESTINY-Gastric01, of the 125 patients with locally advanced or metastatic HER2-positive gastric or GEJ adenocarcinoma treated with ENHERTU 6.4 mg/kg, a decrease in neutrophil count was reported in 72% of patients. Fifty-one percent had Grade 3 or 4 decreased neutrophil count. Median time to first onset of decreased neutrophil count was 16 days (range: 4 to 187). Febrile neutropenia was reported in 4.8% of patients.

Left Ventricular Dysfunction

Patients treated with ENHERTU may be at increased risk of developing left ventricular dysfunction. Left ventricular ejection fraction (LVEF) decrease has been observed with anti-HER2 therapies, including ENHERTU. In the 234 patients with unresectable or metastatic HER2-positive breast cancer who received ENHERTU, two cases (0.9%) of asymptomatic LVEF decrease were reported. In DESTINY-Gastric01, of the 125 patients with locally advanced or metastatic HER2-positive gastric or GEJ adenocarcinoma treated with ENHERTU 6.4 mg/kg, no clinical adverse events of heart failure were reported; however, on echocardiography, 8% were found to have asymptomatic Grade 2 decrease in LVEF. Treatment with ENHERTU has not been studied in patients with a history of clinically significant cardiac disease or LVEF <50% prior to initiation of treatment.

Assess LVEF prior to initiation of ENHERTU and at regular intervals during treatment as clinically indicated. When LVEF is >45% and absolute decrease from baseline is 10-20%, continue treatment with ENHERTU. When LVEF is 40-45% and absolute decrease from baseline is <10%, continue treatment with ENHERTU and repeat LVEF assessment within 3 weeks. When LVEF is 40-45% and absolute decrease from baseline is 10-20%, interrupt ENHERTU and repeat LVEF assessment within 3 weeks. If LVEF has not recovered to within 10% from baseline, permanently discontinue ENHERTU. If LVEF recovers to within 10% from baseline, resume treatment with ENHERTU at the same dose. When LVEF is <40% or absolute decrease from baseline is >20%, interrupt ENHERTU and repeat LVEF assessment within 3 weeks. If LVEF of <40% or absolute decrease from baseline of >20% is confirmed, permanently discontinue ENHERTU. Permanently discontinue ENHERTU in patients with symptomatic congestive heart failure.

Embryo-Fetal Toxicity

ENHERTU can cause fetal harm when administered to a pregnant woman. Advise patients of the potential risks to a fetus. Verify the pregnancy status of females of reproductive potential prior to the initiation of ENHERTU. Advise females of reproductive potential to use effective contraception during treatment and for at least 7 months following the last dose of ENHERTU. Advise male patients with female partners of reproductive potential to use effective contraception during treatment with ENHERTU and for at least 4 months after the last dose of ENHERTU.

Additional Dose Modifications

Thrombocytopenia

For Grade 3 thrombocytopenia (platelets <50 to 25 x 10⁹/L) interrupt ENHERTU until resolved to Grade 1 or less, then maintain dose. For Grade 4 thrombocytopenia (platelets <25 x 10⁹/L) interrupt ENHERTU until resolved to Grade 1 or less. Reduce dose by one level.

Adverse Reactions

Metastatic Breast Cancer

The safety of ENHERTU was evaluated in a pooled analysis of 234 patients with unresectable or metastatic HER2-positive breast cancer who received at least one dose of ENHERTU 5.4 mg/kg in DESTINY-Breast01 and Study DS8201-A-J101. ENHERTU was administered by intravenous infusion once every three weeks. The median duration of treatment was 7 months (range: 0.7 to 31).

Serious adverse reactions occurred in 20% of patients receiving ENHERTU. Serious adverse reactions in >1% of patients who received ENHERTU were interstitial lung disease, pneumonia, vomiting, nausea, cellulitis, hypokalemia, and intestinal obstruction. Fatalities due to adverse reactions occurred in 4.3% of patients including interstitial lung disease (2.6%), and the following events occurred in one patient each (0.4%): acute hepatic failure/acute kidney injury, general physical health deterioration, pneumonia, and hemorrhagic shock.

ENHERTU was permanently discontinued in 9% of patients, of which ILD accounted for 6%. Dose interruptions due to adverse reactions occurred in 33% of patients treated with ENHERTU. The most frequent adverse reactions (>2%) associated with dose interruption were neutropenia, anemia, thrombocytopenia, leukopenia, upper respiratory tract infection, fatigue, nausea, and ILD. Dose reductions occurred in 18% of patients treated with ENHERTU. The most frequent adverse reactions (>2%) associated with dose reduction were fatigue, nausea, and neutropenia.

The most common (≥20%) adverse reactions, including laboratory abnormalities, were nausea (79%), white blood cell count decreased (70%), hemoglobin decreased (70%), neutrophil count decreased (62%), fatigue (59%), vomiting (47%), alopecia (46%), aspartate aminotransferase increased (41%), alanine aminotransferase increased (38%), platelet count decreased (37%), constipation (35%), decreased appetite (32%), anemia (31%), diarrhea (29%), hypokalemia (26%), and cough (20%).

Locally Advanced or Metastatic Gastric Cancer

The safety of ENHERTU was evaluated in 187 patients with locally advanced or metastatic HER2-positive gastric or GEJ adenocarcinoma in DESTINY-Gastric01. Patients intravenously received at least one dose of either ENHERTU (N=125) 6.4 mg/kg once every three weeks or either irinotecan (N=55) 150 mg/m² biweekly or paclitaxel (N=7) 80 mg/m² weekly for 3 weeks. The median duration of treatment was 4.6 months (range: 0.7 to 22.3) in the ENHERTU group and 2.8 months (range: 0.5 to 13.1) in the irinotecan/paclitaxel group.

Serious adverse reactions occurred in 44% of patients receiving ENHERTU 6.4 mg/kg. Serious adverse reactions in >2% of patients who received ENHERTU were decreased appetite, ILD, anemia, dehydration, pneumonia, cholestatic jaundice, pyrexia, and tumor hemorrhage. Fatalities due to adverse reactions occurred in 2.4% of patients: disseminated intravascular coagulation, large intestine perforation, and pneumonia occurred in one patient each (0.8%).

ENHERTU was permanently discontinued in 15% of patients, of which ILD accounted for 6%. Dose interruptions due to adverse reactions occurred in 62% of patients treated with ENHERTU. The most frequent adverse reactions (>2%) associated with dose interruption were neutropenia, anemia, decreased appetite, leukopenia, fatigue, thrombocytopenia, ILD, pneumonia, lymphopenia, upper respiratory tract infection, diarrhea, and hypokalemia. Dose reductions occurred in 32% of patients treated with ENHERTU. The most frequent adverse reactions (>2%) associated with dose reduction were neutropenia, decreased appetite, fatigue, nausea, and febrile neutropenia.

The most common (≥20%) adverse reactions, including laboratory abnormalities, were hemoglobin decreased (75%), white blood cell count decreased (74%), neutrophil count decreased (72%), lymphocyte count decreased (70%), platelet count decreased (68%), nausea (63%), decreased appetite (60%), anemia (58%), aspartate aminotransferase increased (58%), fatigue (55%), blood alkaline phosphatase increased (54%), alanine aminotransferase increased (47%), diarrhea (32%), hypokalemia (30%), vomiting (26%), constipation (24%), blood bilirubin increased (24%), pyrexia (24%), and alopecia (22%).

Contacts

Media:

Global/US:
Victoria Amari

Daiichi Sankyo, Inc.

vamari@dsi.com
+1 908 900 3010 (mobile)

EU:
Lydia Worms

Daiichi Sankyo Europe GmbH

lydia.worms@daiichi-sankyo.eu
+49 (89) 7808751 (office)

+49 176 11780861 (mobile)

Japan:
Masashi Kawase

Daiichi Sankyo Co., Ltd.

kawase.masashi.a2@daiichisankyo.co.jp
+81 3 6225 1126 (office)

Investor Relations:
DaiichiSankyoIR@daiichisankyo.co.jp

Read full story here

Submission to FDA was based on positive data from Phase III FIDELIO-DKD study recently published in the New England Journal of Medicine

WHIPPANY, N.J.–(BUSINESS WIRE)–Bayer announced today that the U.S. Food and Drug Administration (FDA) has accepted its New Drug Application (NDA) and granted Priority Review for finerenone, an investigational drug for patients with chronic kidney disease (CKD) and type 2 diabetes (T2D). This regulatory submission was based on Phase III FIDELIO-DKD trial data, which were recently presented at the American Society of Nephrology’s (ASN) Kidney Week Reimagined 2020, and simultaneously published in the October 23, 2020 edition of the New England Journal of Medicine.

Finerenone is a potential first-in-class investigational, non-steroidal, selective mineralocorticoid receptor antagonist (MRA) that demonstrated positive kidney and cardiovascular outcomes in patients with CKD and T2D in the Phase III FIDELIO-DKD study.^1,2,3

“There is currently a significant unmet medical need for the nearly 40 percent of people in the U.S. living with type 2 diabetes who will develop chronic kidney disease. This progressive condition can lead to kidney damage and eventual failure, despite currently available treatments,” said Dr. Michael Devoy, Head of Medical Affairs & Pharmacovigilance of Bayer AG’s Pharmaceuticals Division and Chief Medical Officer. “Based on study data, finerenone offers a potential new strategy to delay CKD progression, while reducing the risk of cardiovascular events. We’re encouraged that the FDA has granted the NDA a Priority Review, as it potentially expedites our ability to make finerenone available to patients.”

The FDA grants Priority Review to medicines that may offer significant improvements in the treatment, diagnosis or prevention of a serious condition. Under a Priority Review designation, the agency’s goal is to take action on a New Drug Application within six months of acceptance, compared to 10 months under standard review.

About Finerenone

Finerenone (BAY 94-8862) is an investigational, non-steroidal, selective mineralocorticoid receptor antagonist (MRA) that has been shown to reduce many of the harmful effects of mineralocorticoid receptor (MR) overactivation.⁵ Mineralocorticoid receptor overactivation is a driver of kidney and cardiovascular damage through inflammatory and fibrotic processes.^6,7

The Phase III program with finerenone in CKD and T2D randomized 13,000 patients across a broad range of disease severity including those with early kidney damage and more advanced stages of kidney disease. It is the largest Phase III clinical trial program to date in CKD and T2D and comprises two studies, evaluating the effect of finerenone versus placebo on top of standard of care on both renal and cardiovascular outcomes.^1,2

About Bayer’s Commitment in Cardiovascular and Kidney Diseases

Bayer is an innovation leader in the area of cardiovascular diseases, with a long-standing commitment to delivering science for a better life by advancing a portfolio of innovative treatments. The heart and the kidneys are closely linked in health and disease, and Bayer is working in a wide range of therapeutic areas on new treatment approaches for cardiovascular and kidney diseases with high unmet medical needs. The cardiology franchise at Bayer already includes a number of products and several other compounds in various stages of preclinical and clinical development. Together, these products reflect the company’s approach to research, which prioritizes targets and pathways with the potential to impact the way that cardiovascular diseases are treated.

About Bayer

Bayer is a global enterprise with core competencies in the life science fields of health care and nutrition. Its products and services are designed to benefit people by supporting efforts to overcome the major challenges presented by a growing and aging global population. At the same time, the Group aims to increase its earning power and create value through innovation and growth. Bayer is committed to the principles of sustainable development, and the Bayer brand stands for trust, reliability and quality throughout the world. In fiscal 2019, the Group employed around 104,000 people and had sales of 43.5 billion euros. Capital expenditures amounted to 2.9 billion euros, R&D expenses to 5.3 billion euros. For more information, go to www.bayer.us.

Find more information at www.pharma.bayer.com
Our online press service is just a click away: www.bayer.us/en/newsroom
Follow us on Facebook: http://www.facebook.com/pharma.bayer
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Forward-Looking Statements

This release may contain forward-looking statements based on current assumptions and forecasts made by Bayer management. Various known and unknown risks, uncertainties and other factors could lead to material differences between the actual future results, financial situation, development or performance of the company and the estimates given here. These factors include those discussed in Bayer’s public reports which are available on the Bayer website at www.bayer.com. The company assumes no liability whatsoever to update these forward-looking statements or to conform them to future events or developments.

^{____________________________}

¹ Data on file.

² Bakris, GL., et al. Effect of Finerenone on Chronic Kidney Disease Outcomes in Type 2 Diabetes. N Engl J Med. 2020 Oct 23. DOI: 10.1056/NEJMoa2025845.

³ Agarwal, R, et al. Steroidal and non-steroidal mineralocorticoid receptor antagonists in cardiorenal medicine. Eur Heart J. 2020;00:1-12.

⁴ Bailey, R, et al.. Chronic kidney disease in US adults with type 2 diabetes: an updated national estimate of prevalence based on Kidney Disease: Improving Global Outcomes (KDIGO) staging. BMC Res Notes. 2014;7:415.

⁵ Kolkhof, P, et al. Steroidal and novel non-steroidal mineralocorticoid receptor antagonists in heart failure and cardiorenal diseases: comparison at bench and bedside. Handb Exp Pharmacol. 2017;243:271-305.

⁶ Bauersachs J, et al. Mineralocorticoid receptor activation and mineralocorticoid receptor antagonist treatment in cardiac and renal diseases. Hypertension. 2015 Feb;65(2):257-63.

⁷ Buonafine, M, et al. Mineralocorticoid Receptor and Cardiovascular Disease. Am J Hypertens. 2018;31(11):1165-1174.

Contacts

Media Contact:
David Patti, +1-973-452-6793

Bayer, U.S. Corporate Communications

david.patti@bayer.com

—New 103,720 ft² Facility to Serve as Headquarters and House 150 Employees in Cranbury, NJ—

—State of the Art R&D Facility to Support Manufacturing Including AAV Drug Product—

—cGMP Production to be Initiated in 2021 for Planned Phase 2 Study of First AAV-based Gene Therapy, RP-A501 for the Treatment of Danon Disease—

CRANBURY, N.J. — (BUSINESS WIRE) — $RCKT #GeneTherapy—Rocket Pharmaceuticals, Inc. (NASDAQ: RCKT), a clinical-stage company advancing an integrated and sustainable pipeline of genetic therapies for rare childhood disorders, today announces the Company’s plans for the buildout of its new Research and Development (R&D) and Chemistry, Manufacturing and Controls (CMC) operation which will also serve as the Company’s new headquarters in Cranbury, New Jersey. This new 103,720 ft² facility will support clinical development of Rocket’s growing pipeline of lentivirus (LV) and adeno-associated virus (AAV) gene therapies from discovery through pivotal trials, with space for potential future expansion and commercialization. This buildout comes on the heels of the Company’s recent successful capital raise of approximately $300 million that provides a cash runway into the second half of 2023.

“Investing in R&D and manufacturing innovation, talent, and capacity through this new world-class facility will allow us to deliver on our mission of bringing five curative gene therapies to rare disease patients by 2025,” said Gaurav Shah, M.D., President and Chief Executive Officer of Rocket. “With data on five clinical programs expected this year, including two that are in registration-enabling trials, these new capabilities will enable us to work with continued urgency and purpose towards bringing transformational therapies to patients.”

“We are collaborating with some of the best scientists and innovators worldwide. This new facility is instrumental in bolstering Rocket’s gene therapy capabilities to rapidly advance multiple platforms and programs efficiently and effectively. Producing clinical drug product will enable greater control of supply, cost, quality, and timing to pave a smoother path toward commercialization,” added Kinnari Patel, Pharm.D., MBA, Chief Operating Officer and Head of Development.

Approximately one-half of the facility is being scaled for AAV Current Good Manufacturing Practice (cGMP) production. The other half features state-of-the-art R&D labs to support the expanding pipeline and Quality Control (QC) laboratories to support CMC development for process and analytics.

Rocket recently reported positive interim Phase 1 results for its first AAV-based gene therapy, RP-A501 for the treatment of Danon Disease. The first cGMP production at this facility will be initiated in 2021 and will be used in a planned Phase 2 registrational study evaluating RP-A501, following the completion of the current Phase 1 trial.

Approximately $300 million secured in public equity offering

On December 14, 2020, Rocket closed an upsized underwritten public offering of 6,035,714 shares of its common stock, inclusive of greenshoe, at the public offering price of $56.00 per share. The offering was ~7.3x oversubscribed based on the initial deal size of $175 million. Rocket intends to use the net proceeds from this offering to further fund the development of its pipeline of gene therapies for rare diseases, including filing for marketing authorization for RP-L201 in the U.S. and Europe, accelerate the buildout of in-house manufacturing capabilities, and for general corporate purposes. This capital raise extends Rocket’s cash runway to the second half of 2023.

About Rocket Pharmaceuticals, Inc.

Rocket Pharmaceuticals, Inc. (NASDAQ: RCKT) is advancing an integrated and sustainable pipeline of genetic therapies that correct the root cause of complex and rare childhood disorders. The Company’s platform-agnostic approach enables it to design the best therapy for each indication, creating potentially transformative options for patients afflicted with rare genetic diseases. Rocket’s clinical programs using lentiviral vector (LVV)-based gene therapy are for the treatment of Fanconi Anemia (FA), a difficult to treat genetic disease that leads to bone marrow failure and potentially cancer, Leukocyte Adhesion Deficiency-I (LAD-I), a severe pediatric genetic disorder that causes recurrent and life-threatening infections which are frequently fatal, Pyruvate Kinase Deficiency (PKD) a rare, monogenic red blood cell disorder resulting in increased red cell destruction and mild to life-threatening anemia, and Infantile Malignant Osteopetrosis (IMO), a bone marrow-derived disorder. Rocket’s first clinical program using adeno-associated virus (AAV)-based gene therapy is for Danon disease, a devastating, pediatric heart failure condition. For more information about Rocket, please visit www.rocketpharma.com.

Rocket Cautionary Statement Regarding Forward-Looking Statements

Various statements in this release concerning Rocket’s future expectations, plans and prospects, including without limitation, Rocket’s expectations regarding the safety, effectiveness and timing of product candidates that Rocket may develop, to treat Fanconi Anemia (FA), Leukocyte Adhesion Deficiency-I (LAD-I), Pyruvate Kinase Deficiency (PKD), Infantile Malignant Osteopetrosis (IMO) and Danon Disease, and the safety, effectiveness and timing of related pre-clinical studies and clinical trials, may constitute forward-looking statements for the purposes of the safe harbor provisions under the Private Securities Litigation Reform Act of 1995 and other federal securities laws and are subject to substantial risks, uncertainties and assumptions. You should not place reliance on these forward-looking statements, which often include words such as “believe,” “expect,” “anticipate,” “intend,” “plan,” “will give,” “estimate,” “seek,” “will,” “may,” “suggest” or similar terms, variations of such terms or the negative of those terms. Although Rocket believes that the expectations reflected in the forward-looking statements are reasonable, Rocket cannot guarantee such outcomes. Actual results may differ materially from those indicated by these forward-looking statements as a result of various important factors, including, without limitation, Rocket’s ability to successfully demonstrate the efficacy and safety of such products and pre-clinical studies and clinical trials, its gene therapy programs, the preclinical and clinical results for its product candidates, which may not support further development and marketing approval, the potential advantages of Rocket’s product candidates, actions of regulatory agencies, which may affect the initiation, timing and progress of pre-clinical studies and clinical trials of its product candidates, Rocket’s and its licensors’ ability to obtain, maintain and protect its and their respective intellectual property, the timing, cost or other aspects of a potential commercial launch of Rocket’s product candidates, Rocket’s ability to manage operating expenses, Rocket’s ability to obtain additional funding to support its business activities and establish and maintain strategic business alliances and new business initiatives, Rocket’s dependence on third parties for development, manufacture, marketing, sales and distribution of product candidates, the outcome of litigation, and unexpected expenditures, as well as those risks more fully discussed in the section entitled “Risk Factors” in Rocket’s Quarterly Report on Form 10-Q for the quarter ended September 30, 2019, filed November 8, 2019 with the SEC. Accordingly, you should not place undue reliance on these forward-looking statements. All such statements speak only as of the date made, and Rocket undertakes no obligation to update or revise publicly any forward-looking statements, whether as a result of new information, future events or otherwise.

Contacts

Claudine Prowse, Ph.D.

SVP, Strategy & Corporate Development

investors@rocketpharma.com

KENILWORTH, N.J.–(BUSINESS WIRE)–$MRK #MRK–Merck (NYSE: MRK), known as MSD outside the United States and Canada, will hold its fourth-quarter and full-year 2020 sales and earnings conference call with institutional investors and analysts at 8:00 a.m. EST on Thursday, Feb. 4. During the call, company executives will provide an overview of Merck’s performance for the quarter.

Investors, journalists and the general public may access a live audio webcast of the call on Merck’s website at https://www.merck.com/investor-relations/events-and-presentations/. A replay of the webcast, along with the sales and earnings news release, presentation and supplemental financial disclosures, will be available at www.merck.com.

Institutional investors and analysts can participate in the call by dialing (833) 353-0277 or toll free (469) 886-1947 and using ID code number 2268598. Members of the media are invited to monitor the call by dialing (833) 353-0277 or toll free (469) 886-1947 and using ID code number 2268598. Journalists who wish to ask questions are requested to contact a member of Merck’s Media Relations team at the conclusion of the call.

About Merck

For more than 125 years, Merck, known as MSD outside of the United States and Canada, has been inventing for life, bringing forward medicines and vaccines for many of the world’s most challenging diseases in pursuit of our mission to save and improve lives. We demonstrate our commitment to patients and population health by increasing access to health care through far-reaching policies, programs and partnerships. Today, Merck continues to be at the forefront of research to prevent and treat diseases that threaten people and animals – including cancer, infectious diseases such as HIV and Ebola, and emerging animal diseases – as we aspire to be the premier research-intensive biopharmaceutical company in the world. For more information, visit www.merck.com and connect with us on Twitter, Facebook, Instagram, YouTube and LinkedIn.

Forward-Looking Statement of Merck & Co., Inc., Kenilworth, N.J., USA

This news release of Merck & Co., Inc., Kenilworth, N.J., USA (the “company”) includes “forward-looking statements” within the meaning of the safe harbor provisions of the U.S. Private Securities Litigation Reform Act of 1995. These statements are based upon the current beliefs and expectations of the company’s management and are subject to significant risks and uncertainties. There can be no guarantees with respect to pipeline products that the products will receive the necessary regulatory approvals or that they will prove to be commercially successful. If underlying assumptions prove inaccurate or risks or uncertainties materialize, actual results may differ materially from those set forth in the forward-looking statements.

Risks and uncertainties include but are not limited to, general industry conditions and competition; general economic factors, including interest rate and currency exchange rate fluctuations; the impact of the global outbreak of novel coronavirus disease (COVID-19); the impact of pharmaceutical industry regulation and health care legislation in the United States and internationally; global trends toward health care cost containment; technological advances, new products and patents attained by competitors; challenges inherent in new product development, including obtaining regulatory approval; the company’s ability to accurately predict future market conditions; manufacturing difficulties or delays; financial instability of international economies and sovereign risk; dependence on the effectiveness of the company’s patents and other protections for innovative products; and the exposure to litigation, including patent litigation, and/or regulatory actions.

The company undertakes no obligation to publicly update any forward-looking statement, whether as a result of new information, future events or otherwise. Additional factors that could cause results to differ materially from those described in the forward-looking statements can be found in the company’s 2019 Annual Report on Form 10-K and the company’s other filings with the Securities and Exchange Commission (SEC) available at the SEC’s Internet site (www.sec.gov).

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PRINCETON, N.J. — (BUSINESS WIRE) — $BMY #BMS—Bristol Myers Squibb (NYSE:BMY) today announced that the European Medicines Agency (EMA) validated its Marketing Authorization Application (MAA) for Opdivo (nivolumab) as an adjuvant treatment for esophageal or gastroesophageal junction (GEJ) cancer in adult patients with residual pathologic disease after neoadjuvant chemoradiotherapy (CRT) and resection. Validation of the application confirms that submission is complete, and the EMA’s centralized review process will begin.

The application is based on results from the Phase 3 CheckMate -577 trial, in which Opdivo doubled median disease-free survival (DFS) – its primary endpoint – in patients with esophageal or GEJ cancer, following neoadjuvant CRT and tumor resection. The safety profile of Opdivo as adjuvant therapy in the CheckMate -577 trial was consistent with that reported in previous Opdivo studies.

“The majority of esophageal cancer patients with localized disease who are treated with both chemotherapy and surgery do not achieve complete response. Their risk of recurrence is unacceptably high and the establishment of more effective treatment options is essential,” said Ian M. Waxman, M.D., development lead, gastrointestinal cancers, Bristol Myers Squibb. “The EMA’s decision to validate our application represents important progress for the esophageal cancer community, and we look forward to potentially bringing Opdivo to patients in the EU who may benefit.”

Bristol Myers Squibb thanks the patients and investigators who have been involved in the CheckMate -577 trial.

About CheckMate -577

CheckMate -577 is a Phase 3 randomized, multi-center, double-blind study evaluating Opdivo as an adjuvant therapy in patients with resected esophageal or gastroesophageal junction (GEJ) cancer who have received neoadjuvant chemoradiotherapy (CRT) and have not achieved a pathological complete response. The primary endpoint of the trial is disease-free survival (DFS) and the secondary endpoint is overall survival (OS). Following neoadjuvant CRT and complete tumor surgical resection (also known as trimodality therapy), a total of 794 patients were randomized to receive placebo (n=262) or Opdivo (n=532) 240 mg by intravenous infusion every two weeks for 16 weeks followed by placebo or Opdivo 480 mg every four weeks until disease recurrence, unacceptable toxicity or withdrawal of consent, with a maximum of one year total treatment duration. Follow up for OS is ongoing.

About Esophageal Cancer

Esophageal cancer is the seventh most common cancer and the sixth leading cause of death from cancer worldwide, with approximately 572,000 new cases and over 508,000 deaths in 2018. The two most common types of esophageal cancer are squamous cell carcinoma and adenocarcinoma, which account for approximately 85% and 14% of all esophageal cancers, respectively, though esophageal tumor histology can vary by region with the highest rate of esophageal adenocarcinoma occurring in North America (65%). 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: Creating a Better Future for People with Cancer

Bristol Myers Squibb is inspired by a single vision — transforming people’s lives through science. The goal of the company’s cancer research is to deliver medicines that offer each patient a better, healthier life and to make cure a possibility. Building on a legacy across a broad range of cancers that have changed survival expectations for many, Bristol Myers Squibb researchers are exploring new frontiers in personalized medicine, and through innovative digital platforms, are turning data into insights that sharpen their focus. Deep scientific expertise, cutting-edge capabilities and discovery platforms enable the company to look at cancer from every angle. Cancer can have a relentless grasp on many parts of a patient’s life, and Bristol Myers Squibb is committed to taking actions to address all aspects of care, from diagnosis to survivorship. Because as a leader in cancer care, Bristol Myers Squibb is working to empower all people with cancer to have a better future.

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.

INDICATIONS

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), in combination with YERVOY^® (ipilimumab), is indicated for the first-line treatment of adult patients with metastatic non-small cell lung cancer (NSCLC) whose tumors express PD-L1 (≥1%) as determined by an FDA-approved test, with no EGFR or ALK genomic tumor aberrations.

OPDIVO^® (nivolumab), in combination with YERVOY^® (ipilimumab) and 2 cycles of platinum-doublet chemotherapy, is indicated for the first-line treatment of adult patients with metastatic or recurrent non-small cell lung cancer (NSCLC), with no EGFR or ALK genomic tumor aberrations.

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), in combination with YERVOY^® (ipilimumab), is indicated for the first-line treatment of adult patients with unresectable malignant pleural mesothelioma (MPM).

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 overall response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials.

OPDIVO^® (nivolumab), in combination with YERVOY^® (ipilimumab), 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 overall response rate and duration 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.

OPDIVO^® (nivolumab) is indicated for the treatment of patients with unresectable advanced, recurrent or metastatic esophageal squamous cell carcinoma (ESCC) after prior fluoropyrimidine- and platinum-based chemotherapy.

IMPORTANT SAFETY INFORMATION

Severe and Fatal Immune-Mediated Adverse Reactions

Immune-mediated adverse reactions listed herein may not include all possible severe and fatal immune-mediated adverse reactions.

Immune-mediated adverse reactions, which may be severe or fatal, can occur in any organ system or tissue. While immune-mediated adverse reactions usually manifest during treatment, they can also occur after discontinuation of OPDIVO or YERVOY. Early identification and management are essential to ensure safe use of OPDIVO and YERVOY. Monitor for signs and symptoms that may be clinical manifestations of underlying immune-mediated adverse reactions. Evaluate clinical chemistries including liver enzymes, creatinine, adrenocorticotropic hormone (ACTH) level, and thyroid function at baseline and periodically during treatment with OPDIVO and before each dose of YERVOY. In cases of suspected immune-mediated adverse reactions, initiate appropriate workup to exclude alternative etiologies, including infection. Institute medical management promptly, including specialty consultation as appropriate.

Withhold or permanently discontinue OPDIVO and YERVOY depending on severity (please see section 2 Dosage and Administration in the accompanying Full Prescribing Information). In general, if OPDIVO or YERVOY interruption or discontinuation is required, administer systemic corticosteroid therapy (1 to 2 mg/kg/day prednisone or equivalent) until improvement to Grade 1 or less. Upon improvement to Grade 1 or less, initiate corticosteroid taper and continue to taper over at least 1 month. Consider administration of other systemic immunosuppressants in patients whose immune-mediated adverse reactions are not controlled with corticosteroid therapy. Toxicity management guidelines for adverse reactions that do not necessarily require systemic steroids (e.g., endocrinopathies and dermatologic reactions) are discussed below.

Immune-Mediated Pneumonitis

OPDIVO and YERVOY can cause immune-mediated pneumonitis. The incidence of pneumonitis is higher in patients who have received prior thoracic radiation. In patients receiving OPDIVO monotherapy, immune-mediated pneumonitis occurred in 3.1% (61/1994) of patients, including Grade 4 (<0.1%), Grade 3 (0.9%), and Grade 2 (2.1%). In HCC patients receiving OPDIVO 1 mg/kg with YERVOY 3 mg/kg every 3 weeks, immune-mediated pneumonitis occurred in 10% (5/49) of patients. In patients receiving OPDIVO 3 mg/kg with YERVOY 1 mg/kg every 3 weeks, immune-mediated pneumonitis occurred in 3.9% (26/666) of patients, including Grade 3 (1.4%) and Grade 2 (2.6%). In NSCLC patients receiving OPDIVO 3 mg/kg every 2 weeks with YERVOY 1 mg/kg every 6 weeks, immune-mediated pneumonitis occurred in 9% (50/576) of patients, including Grade 4 (0.5%), Grade 3 (3.5%), and Grade 2 (4.0%). Four patients (0.7%) died due to pneumonitis.

Immune-Mediated Colitis

OPDIVO and YERVOY can cause immune-mediated colitis, which may be fatal. A common symptom included in the definition of colitis was diarrhea. 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. In patients receiving OPDIVO monotherapy, immune-mediated colitis occurred in 2.9% (58/1994) of patients, including Grade 3 (1.7%) and Grade 2 (1%). In patients receiving OPDIVO 1 mg/kg with YERVOY 3 mg/kg every 3 weeks, immune-mediated colitis occurred in 25% (115/456) of patients, including Grade 4 (0.4%), Grade 3 (14%) and Grade 2 (8%). In patients receiving OPDIVO 3 mg/kg with YERVOY 1 mg/kg every 3 weeks, immune-mediated colitis occurred in 9% (60/666) of patients, including Grade 3 (4.4%) and Grade 2 (3.7%).

In a separate Phase 3 trial of YERVOY 3 mg/kg monotherapy, immune-mediated colitis occurred in 12% (62/511) of patients, including Grade 3-5 (7%) and Grade 2 (5%).

Immune-Mediated Hepatitis

OPDIVO and YERVOY can cause immune-mediated hepatitis. In patients receiving OPDIVO monotherapy, immune-mediated hepatitis occurred in 1.8% (35/1994) of patients, including Grade 4 (0.2%), Grade 3 (1.3%), and Grade 2 (0.4%). In patients receiving OPDIVO 1 mg/ kg with YERVOY 3 mg/kg every 3 weeks, immune-mediated hepatitis occurred in 15% (70/456) of patients, including Grade 4 (2.4%), Grade 3 (11%), and Grade 2 (1.8%). In patients receiving OPDIVO 3 mg/kg with YERVOY 1 mg/kg every 3 weeks, immune-mediated hepatitis occurred in 7% (48/666) of patients, including Grade 4 (1.2%), Grade 3 (4.9%), and Grade 2 (0.4%).

In a separate Phase 3 trial of YERVOY 3 mg/kg monotherapy, immune-mediated hepatitis occurred in 4.1% (21/511) of patients, including Grade 3-5 (1.6%) and Grade 2 (2.5%).

Immune-Mediated Endocrinopathies

OPDIVO and YERVOY can cause primary or secondary adrenal insufficiency, immune-mediated hypophysitis, immune-mediated thyroid disorders, and Type 1 diabetes mellitus, which can present with diabetic ketoacidosis. Withhold OPDIVO and YERVOY depending on severity (please see section 2 Dosage and Administration in the accompanying Full Prescribing Information). For Grade 2 or higher adrenal insufficiency, initiate symptomatic treatment, including hormone replacement as clinically indicated. Hypophysitis can present with acute symptoms associated with mass effect such as headache, photophobia, or visual field defects. Hypophysitis can cause hypopituitarism; initiate hormone replacement as clinically indicated. Thyroiditis can present with or without endocrinopathy. Hypothyroidism can follow hyperthyroidism; initiate hormone replacement or medical management as clinically indicated. Monitor patients for hyperglycemia or other signs and symptoms of diabetes; initiate treatment with insulin as clinically indicated.

In patients receiving OPDIVO monotherapy, adrenal insufficiency occurred in 1% (20/1994), including Grade 3 (0.4%) and Grade 2 (0.6%). In patients receiving OPDIVO 1 mg/kg with YERVOY 3 mg/kg every 3 weeks, adrenal insufficiency occurred in 8% (35/456), including Grade 4 (0.2%), Grade 3 (2.4%), and Grade 2 (4.2%). In patients receiving OPDIVO 3 mg/kg with YERVOY 1 mg/kg every 3 weeks, adrenal insufficiency occurred in 7% (48/666) of patients, including Grade 4 (0.3%), Grade 3 (2.5%), and Grade 2 (4.1%).

In patients receiving OPDIVO monotherapy, hypophysitis occurred in 0.6% (12/1994) of patients, including Grade 3 (0.2%) and Grade 2 (0.3%). In patients receiving OPDIVO 1 mg/kg with YERVOY 3 mg/kg every 3 weeks, hypophysitis occurred in 9% (42/456), including Grade 3 (2.4%) and Grade 2 (6%). In patients receiving OPDIVO 3 mg/kg with YERVOY 1 mg/kg every 3 weeks, hypophysitis occurred in 4.4% (29/666) of patients, including Grade 4 (0.3%), Grade 3 (2.4%), and Grade 2 (0.9%).

In patients receiving OPDIVO monotherapy, thyroiditis occurred in 0.6% (12/1994) of patients, including Grade 2 (0.2%). In patients receiving OPDIVO 3 mg/kg with YERVOY 1 mg/kg every 3 weeks, thyroiditis occurred in 2.7% (22/666) of patients, including Grade 3 (4.5%) and Grade 2 (2.2%).

In patients receiving OPDIVO monotherapy, hyperthyroidism occurred in 2.7% (54/1994) of patients, including Grade 3 (<0.1%) and Grade 2 (1.2%). In patients receiving OPDIVO 1 mg/kg with YERVOY 3 mg/kg every 3 weeks, hyperthyroidism occurred in 9% (42/456) of patients, including Grade 3, (0.9%) and Grade 2 (4.2%). In patients receiving OPDIVO 3 mg/kg with YERVOY 1 mg/kg every 3 weeks, hyperthyroidism occurred in 12% (80/666) of patients, including Grade 3 (0.6%), and Grade 2 (4.5%).

In patients receiving OPDIVO monotherapy, hypothyroidism occurred in 8% (163/1994) of patients, including Grade 3 (0.2%) and Grade 2 (4.8%). In patients receiving OPDIVO 1 mg/kg with YERVOY 3 mg/kg every 3 weeks, hypothyroidism occurred in 20% (91/456) of patients, including Grade 3 (0.4%) and Grade 2 (11%). In patients receiving OPDIVO 3 mg/kg with YERVOY 1 mg/kg every 3 weeks, hypothyroidism occurred in 18% (122/666) of patients, including Grade 3 (0.6%) and Grade 2 (11%).

In patients receiving OPDIVO monotherapy, diabetes occurred in 0.9% (17/1994) of patients, including Grade 3 (0.4%) and Grade 2 (0.3%), and 2 cases of diabetic ketoacidosis. In patients receiving OPDIVO 3 mg/kg with YERVOY 1 mg/kg every 3 weeks, diabetes occurred in 2.7% (15/666) of patients, including Grade 4 (0.6%), Grade 3 (0.3%), and Grade 2 (0.9%).

In a separate Phase 3 trial of YERVOY 3 mg/kg monotherapy, Grade 2-5 immune-mediated endocrinopathies occurred in 4% (21/511) of patients. Severe to life-threatening (Grade 3-4) endocrinopathies 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. Moderate (Grade 2) endocrinopathy occurred in 12 patients (2.3%), including hypothyroidism, adrenal insufficiency, hypopituitarism, hyperthyroidism and Cushing’s syndrome.

Immune-Mediated Nephritis with Renal Dysfunction

OPDIVO and YERVOY can cause immune-mediated nephritis. In patients receiving OPDIVO monotherapy, immune-mediated nephritis and renal dysfunction occurred in 1.2% (23/1994) of patients, including Grade 4 (<0.1%), Grade 3 (0.5%), and Grade 2 (0.6%). In patients receiving OPDIVO 3 mg/kg with YERVOY 1 mg/kg every 3 weeks, immune-mediated nephritis with renal dysfunction occurred in 4.1% (27/666) of patients, including Grade 4 (0.6%), Grade 3 (1.1%), and Grade 2 (2.2%).

Immune-Mediated Dermatologic Adverse Reactions

OPDIVO can cause immune-mediated rash or dermatitis. Exfoliative dermatitis, including Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), and drug rash with eosinophilia and systemic symptoms (DRESS) has occurred with PD-1/PD-L1 blocking antibodies. Topical emollients and/or topical corticosteroids may be adequate to treat mild to moderate nonexfoliative rashes.

YERVOY can cause immune-mediated rash or dermatitis, including bullous and exfoliative dermatitis, SJS, TEN, and DRESS. Topical emollients and/or topical corticosteroids may be adequate to treat mild to moderate non-bullous/exfoliative rashes.

Withhold or permanently discontinue OPDIVO and YERVOY depending on severity (please see section 2 Dosage and Administration in the accompanying Full Prescribing Information).

In patients receiving OPDIVO monotherapy, immune-mediated rash occurred in 9% (171/1994) of patients, including Grade 3 (1.1%) and Grade 2 (2.2%). In patients receiving OPDIVO 1 mg/kg with YERVOY 3 mg/kg every 3 weeks, immune-mediated rash occurred in 28% (127/456) of patients, including Grade 3 (4.8%) and Grade 2 (10%). In patients receiving OPDIVO 3 mg/kg with YERVOY 1 mg/kg every 3 weeks, immune-mediated rash occurred in 16% (108/666) of patients, including Grade 3 (3.5%) and Grade 2 (4.2%).

In a separate Phase 3 trial of YERVOY 3 mg/kg monotherapy, immune-mediated rash occurred in 15% (76/511) of patients, including Grade 3-5 (2.5%) and Grade 2 (12%).

Other Immune-Mediated Adverse Reactions

The following clinically significant immune-mediated adverse reactions occurred at an incidence of <1% (unless otherwise noted) in patients who received OPDIVO monotherapy or OPDIVO in combination with YERVOY or were reported with the use of other PD-1/PD-L1 blocking antibodies. Severe or fatal cases have been reported for some of these adverse reactions: cardiac/vascular: myocarditis, pericarditis, vasculitis; nervous system: meningitis, encephalitis, myelitis and demyelination, myasthenic syndrome/myasthenia gravis (including exacerbation), Guillain-Barré syndrome, nerve paresis, autoimmune neuropathy; ocular: uveitis, iritis, and other ocular infla

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PRINCETON, N.J.–(BUSINESS WIRE)–$BMY #BMS—Bristol Myers Squibb (NYSE: BMY) today announced that the Biologics License Application (BLA) for lisocabtagene maraleucel (liso-cel) for the treatment of adults with relapsed or refractory (R/R) large B-cell lymphoma after at least two prior therapies remains under review by the U.S. Food and Drug Administration (FDA) and the company has not received a decision. As previously announced, the FDA has not provided a new action date for this application. Bristol Myers Squibb continues to work closely with the FDA to support the ongoing review of the BLA for liso-cel and is committed to bringing this therapy to patients.

Since the FDA approval of liso-cel did not occur by December 31, 2020, one of the three required milestones for payment of the Bristol Myers Squibb Contingent Value Right (CVR) (NYSE: BMY-RT) was not met. As a result, on January 1, 2021, the Contingent Value Rights Agreement (CVR Agreement), pursuant to which the CVRs were issued, terminated automatically in accordance with its terms and the CVRs are no longer eligible for payment under the CVR Agreement. The CVRs will no longer trade on the NYSE.

For additional information, please refer to: https://news.bms.com/news/corporate-financial/2021/Bristol-Myers-Squibb-Statement-on-Status-of-Liso-cel-Application-and-Contingent-Value-Rights/default.aspx or call EQ Shareowner Services at 1-833-503-4131.

Bristol Myers Squibb: Creating a Better Future for People with Cancer

Bristol Myers Squibb is inspired by a single vision — transforming people’s lives through science. The goal of the company’s cancer research is to deliver medicines that offer each patient a better, healthier life and to make cure a possibility. Building on a legacy across a broad range of cancers that have changed survival expectations for many, Bristol Myers Squibb researchers are exploring new frontiers in personalized medicine, and through innovative digital platforms, are turning data into insights that sharpen their focus. Deep scientific expertise, cutting-edge capabilities and discovery platforms enable the company to look at cancer from every angle. Cancer can have a relentless grasp on many parts of a patient’s life, and Bristol Myers Squibb is committed to taking actions to address all aspects of care, from diagnosis to survivorship. Because as a leader in cancer care, Bristol Myers Squibb is working to empower all people with cancer to have a better future.

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.

Juno Therapeutics, Inc. is a wholly owned subsidiary 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.

Bristol Myers Squibb 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, whether liso-cel will be approved by the FDA. 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, 2019, 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.

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timothy.power@bms.com

Marketing Authorization Application is supported by positive results from the pivotal Phase 3 True North study evaluating oral Zeposia (ozanimod) in adults with moderately to severely active ulcerative colitis

If approved, Zeposia would be the first oral sphingosine-1-phosphate (S1P) receptor modulator for the treatment of ulcerative colitis

PRINCETON, N.J.–(BUSINESS WIRE)–$BMY #BMS—Bristol Myers Squibb (NYSE:BMY) today announced that the European Medicines Agency (EMA) has validated its Marketing Authorization Application (MAA) for Zeposia (ozanimod) for the treatment of adults with moderately to severely active ulcerative colitis (UC). Validation of the application confirms the submission is complete and begins the EMA’s centralized review process.

The MAA submitted to the EMA is based on results from True North, a pivotal, placebo-controlled Phase 3 trial evaluating Zeposia as an induction and maintenance therapy in adults with moderately to severely active UC. True North met both primary endpoints, demonstrating highly statistically significant and clinically meaningful results for clinical remission compared to placebo at induction at Week 10 and in maintenance at Week 52. The overall safety observed in True North was consistent with the known safety profile for Zeposia in approved labeling.

“Ulcerative colitis is an unpredictable and potentially debilitating disease, and many patients cycle through different therapies as they try to manage their disease,” said Mary Beth Harler, M.D., head of Immunology and Fibrosis Development, Bristol Myers Squibb. “This validation is an important step toward making Zeposia available to eligible patients in the European Union, who are in need of new treatment options offering proven efficacy and safety, as well as oral administration.”

About True North

True North is a Phase 3, multicenter, randomized, double-blind, placebo-controlled trial comparing the efficacy and safety of Zeposia 1mg in patients with moderately to severely active ulcerative colitis who did not adequately respond to prior treatment. In the induction phase, a total of 645 patients were randomized to receive Zeposia (n=429) or placebo (n=216), of whom 94% and 89%, respectively, completed the induction period. At study entry, mean age was 42 years, 60% were male and mean disease duration was 7 years; patient characteristics were well-balanced across treatment groups. Cohort 1 patients were randomized 2:1 to Zeposia or placebo and treated once daily for 10 weeks. Cohort 2 (n=367) was an open-label arm, and included to allow adequate patient numbers for the maintenance phase of the trial. Cohort 2 patients were treated once daily with Zeposia for 10 weeks.

For the maintenance phase, 457 patients were re-randomized to maintenance treatment with either Zeposia (n=230) or placebo (n=227). Of these, 80% and 54.6% of patients who received Zeposia and placebo, respectively, completed the study; disease relapse (13.5% Zeposia, 33.9% placebo) was the most common reason for discontinuation. Patients on Zeposia from either Cohort 1 or 2 who achieved clinical response in the induction phase at Week 10 were re-randomized 1:1 to Zeposia or placebo through Week 52. Patients on placebo who achieved clinical response in the induction phase at Week 10 remained on placebo during this blinded maintenance phase.

In Cohort 1 of the induction phase and in the re-randomized patient group in the maintenance phase, 30% of patients had prior TNF-inhibitor exposure.

All eligible patients were rolled into an open-label extension trial, which is ongoing and designed to assess the longer-term profile of Zeposia for the treatment of moderately to severely active ulcerative colitis.

The primary endpoints in True North are the proportion of patients in clinical remission based on a composite clinical and endoscopic score (3-component Mayo Score) at Week 10 in the induction phase, and at Week 52 for the maintenance phase. Secondary endpoints include the proportion of patients achieving clinical response at Week 10 and Week 52, the proportion of patients with endoscopic improvement (endoscopy score ≤1) at Week 10 and Week 52, the proportion of patients with mucosal healing at Week 10 and Week 52, and clinical remission at Week 52 in patients that were in remission at Week 10. In this study, mucosal healing is defined as endoscopic improvement with histologic remission. More information can be found on www.clinicaltrials.gov, NCT02435992.

About Ulcerative Colitis

Ulcerative colitis, a chronic inflammatory bowel disease (IBD), is characterized by an abnormal, prolonged immune response that creates long-lasting inflammation and ulcers (sores) in the mucosa (lining) of the large intestine (colon) or rectum. Symptoms, including bloody stools, severe diarrhea and frequent abdominal pain, usually develop over time rather than suddenly. Ulcerative colitis has a major impact on patients’ health-related quality of life, including physical functioning, social and emotional well-being and ability to work. Many patients have an inadequate response or do not respond at all to currently available therapies. It is estimated that approximately 12.6 million people worldwide have IBD.

About Zeposia (ozanimod)

Zeposia (ozanimod) is an oral, sphingosine-1-phosphate (S1P) receptor modulator that binds with high affinity to S1P receptors 1 and 5. Zeposia reduces the capacity of lymphocytes to exit from lymph nodes, reducing the number of circulating lymphocytes in peripheral blood. The mechanism by which Zeposia exerts therapeutic effects in ulcerative colitis is unknown but may involve the reduction of lymphocyte migration into the inflamed intestinal mucosa.

Bristol Myers Squibb is continuing to evaluate Zeposia in an open-label extension trial, which is ongoing and designed to assess the longer-term profile of Zeposia for the treatment of moderately to severely active ulcerative colitis. The company is also investigating Zeposia for the treatment of moderately to severely active Crohn’s disease in the ongoing Phase 3 YELLOWSTONE clinical trial program.

Zeposia was approved by the U.S. Food and Drug Administration (FDA) for the treatment of adults with relapsing forms of multiple sclerosis (RMS) in March 2020. The European Commission approved Zeposia for the treatment of adult patients with relapsing remitting multiple sclerosis (RRMS) with active disease as defined by clinical or imaging features in May 2020. Zeposia is not approved for the treatment of ulcerative colitis in any country.

U.S. FDA-APPROVED INDICATION FOR ZEPOSIA

ZEPOSIA is indicated for the treatment of relapsing forms of multiple sclerosis (MS), to include clinically isolated syndrome, relapsing-remitting disease, and active secondary progressive disease, in adults.

IMPORTANT SAFETY INFORMATION

Contraindications:

• Patients who in the last 6 months, experienced myocardial infarction, unstable angina, stroke, transient ischemic attack (TIA), decompensated heart failure requiring hospitalization, or Class III/IV heart failure or have a presence of Mobitz type II second or third-degree atrioventricular (AV) block, sick sinus syndrome, or sino-atrial, unless the patient has a functioning pacemaker
• Patients with severe untreated sleep apnea
• Patients taking a monoamine oxidase (MAO) inhibitor

Infections: ZEPOSIA may increase the susceptibility to infections. Life-threatening and rare fatal infections have occurred in patients receiving ZEPOSIA. Obtain a recent (i.e., within 6 months or after discontinuation of prior MS therapy) complete blood count (CBC) including lymphocyte count before initiation of ZEPOSIA. Delay initiation of ZEPOSIA in patients with an active infection until the infection is resolved. Consider interruption of treatment with ZEPOSIA if a patient develops a serious infection. Continue monitoring for infections up to 3 months after discontinuing ZEPOSIA

• Herpes zoster was reported as an adverse reaction in ZEPOSIA -treated patients. Herpes simplex encephalitis and varicella zoster meningitis have been reported with sphingosine 1-phosphate (S1P) receptor modulators. Patients without a healthcare professional-confirmed history of varicella (chickenpox), or without documentation of a full course of vaccination against varicella zoster virus (VZV), should be tested for antibodies to VZV before initiating ZEPOSIA. A full course of vaccination for antibody-negative patients with varicella vaccine is recommended prior to commencing treatment with ZEPOSIA
• Cases of fatal cryptococcal meningitis (CM) were reported in patients treated with another S1P receptor modulator. If CM is suspected, ZEPOSIA should be suspended until cryptococcal infection has been excluded. If CM is diagnosed, appropriate treatment should be initiated.
• Progressive Multifocal Leukoencephalopathy (PML) is an opportunistic viral infection of the brain that typically occurs in patients who are immunocompromised, and that usually leads to death or severe disability. No cases of PML were identified in active-controlled MS clinical trials with ZEPOSIA. PML has been reported in patients treated with S1P receptor modulators and other MS therapies and has been associated with some risk factors. If PML is suspected, withhold ZEPOSIA and perform an appropriate diagnostic evaluation. If confirmed, treatment with ZEPOSIA should be discontinued
• In clinical studies, patients who received ZEPOSIA were not to receive concomitant treatment with antineoplastic, non-corticosteroid immunosuppressive, or immune-modulating therapies used for treatment of MS. Concomitant use of ZEPOSIA with any of these therapies would be expected to increase the risk of immunosuppression. When switching to ZEPOSIA from immunosuppressive medications, consider the duration of their effects and their mode of action to avoid unintended additive immunosuppressive effects
• Use of live attenuated vaccines should be avoided during and for 3 months after treatment with ZEPOSIA. If live attenuated vaccine immunizations are required, administer at least 1 month prior to initiation of ZEPOSIA

Bradyarrhythmia and Atrioventricular Conduction Delays: Since initiation of ZEPOSIA may result in a transient decrease in heart rate and atrioventricular conduction delays, dose titration is recommended to help reduce cardiac effects. Initiation of ZEPOSIA without dose escalation may result in greater decreases in heart rate. If treatment with ZEPOSIA is considered, advice from a cardiologist should be sought for those individuals:

• with significant QT prolongation
• with arrhythmias requiring treatment with Class 1a or III anti-arrhythmic drugs
• with ischemic heart disease, heart failure, history of cardiac arrest or myocardial infarction, cerebrovascular disease, and uncontrolled hypertension
• with a history of Mobitz type II second-degree or higher AV block, sick-sinus syndrome, or sinoatrial heart block

Liver Injury: Elevations of aminotransferases may occur in patients receiving ZEPOSIA. Obtain liver function tests, if not recently available (i.e., within 6 months), before initiation of ZEPOSIA. Patients who develop symptoms suggestive of hepatic dysfunction should have hepatic enzymes checked and ZEPOSIA should be discontinued if significant liver injury is confirmed. Caution should be exercised when using ZEPOSIA in patients with history of significant liver disease

Fetal Risk: There are no adequate and well-controlled studies in pregnant women. Based on animal studies, ZEPOSIA may cause fetal harm. Women of childbearing potential should use effective contraception to avoid pregnancy during treatment and for 3 months after stopping ZEPOSIA

Increased Blood Pressure: Increase in systolic pressure was observed after about 3 months of treatment and persisted throughout treatment. Blood pressure should be monitored during treatment and managed appropriately. Certain foods that may contain very high amounts of tyramine could cause severe hypertension in patients taking ZEPOSIA. Patients should be advised to avoid foods containing a very large amount of tyramine while taking ZEPOSIA

Respiratory Effects: ZEPOSIA may cause a decline in pulmonary function. Spirometric evaluation of respiratory function should be performed during therapy, if clinically indicated

Macular edema: S1P modulators have been associated with an increased risk of macular edema. Patients with a history of uveitis or diabetes mellitus are at increased risk. Patients with a history of these conditions should have an ophthalmic evaluation of the fundus, including the macula, prior to treatment initiation and regular follow-up examinations. An ophthalmic evaluation is recommended in all patients at any time if there is a change in vision. Continued use of ZEPOSIA in patients with macular edema has not been evaluated; potential benefits and risks for the individual patient should be considered if deciding whether ZEPOSIA should be discontinued

Posterior Reversible Encephalopathy Syndrome (PRES): Rare cases of PRES have been reported in patients receiving a S1P receptor modulator. If a ZEPOSIA-treated patient develops unexpected neurological or psychiatric symptoms or any symptom/sign suggestive of an increase in intracranial pressure, a complete physical and neurological examination should be conducted. Symptoms of PRES are usually reversible but may evolve into ischemic stroke or cerebral hemorrhage. Delay in diagnosis and treatment may lead to permanent neurological sequelae. If PRES is suspected, treatment with ZEPOSIA should be discontinued

Unintended Additive Immunosuppressive Effects from Prior Immunosuppressive or Immune-Modulating Drugs: When switching from drugs with prolonged immune effects, the half-life and mode of action of these drugs must be considered to avoid unintended additive immunosuppressive effects while at the same time minimizing risk of disease reactivation. Initiating treatment with ZEPOSIA after treatment with alemtuzumab is not recommended

Severe Increase in Disability After Stopping ZEPOSIA: Severe exacerbation of disease, including disease rebound, has been rarely reported after discontinuation of a S1P receptor modulator. The possibility of severe exacerbation of disease should be considered after stopping ZEPOSIA treatment so patients should be monitored upon discontinuation

Immune System Effects After Stopping ZEPOSIA: After discontinuing ZEPOSIA, the median time for lymphocyte counts to return to the normal range was 30 days with approximately 90% of patients in the normal range within 3 months. Use of immunosuppressants within this period may lead to an additive effect on the immune system, therefore caution should be applied when initiating other drugs 4 weeks after the last dose of ZEPOSIA

Most common Adverse Reactions (≥ 4%): upper respiratory infection, hepatic transaminase elevation, orthostatic hypotension, urinary tract infection, back pain, and hypertension.

For additional safety information, please see the full Prescribing Information and Medication Guide.

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, that Zeposia (ozanimod) may not receive regulatory approval for the additional indication described in this release and, if approved, 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, 2019, 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.

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Bristol Myers Squibb

Media Inquiries:
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Kirby Hosea

Kirby.Hosea@bms.com

Investors:
Tim Power

609-252-7509

Timothy.Power@bms.com

Nina Goworek

908-673-9711

Nina.Goworek@bms.com

EOM developing IND for evaluating EOM613 safety and efficacy to treat the most severe effects of COVID-19, including ARDS

MONTVALE, N.J.–(BUSINESS WIRE)–EOM Pharmaceuticals, Inc., a privately held, clinical-stage company, today announced it has filed a pre-Investigational New Drug Application (pre-IND) meeting request and complete pre-IND briefing documents with the U.S. Food and Drug Administration (FDA) to discuss the company’s plans to evaluate the safety and efficacy of its dual-acting, broad-spectrum immunomodulator drug candidate EOM613 in a Phase 2 clinical trial treating complications of hospitalized COVID-19 patients, including Acute Respiratory Distress Syndrome (ARDS).

The pre-IND meeting request is supported by previously completed Phase 2 clinical trials with EOM613* in cachexic AIDS patients and advanced cancer patients with cachexia, a cytokine- and chemokine-related body wasting syndrome. In those studies, EOM613 treatment was shown to be both safe and capable of mitigating the cytokine- and chemokine-driven symptoms of cachexia, stabilizing or increasing patient weight, and also improving quality-of-life measures such as the Karnofsky Performance Status and Simmonds Functional assessment scores.^1,2,3,4,5

“We are pleased to have taken this important step in advancing our EOM613 COVID-19 program as we pursue EOM613 as the first dual-acting, broad-spectrum immunomodulator designed to treat infection-related hyperimmune reactions and autoimmune disorders,” said Irach B. Taraporewala, Ph.D., EOM Chief Executive Officer and Director. “We look forward to finalizing our Phase 2 clinical study design and protocol for EOM613 with the advice and guidance of the FDA and to initiating our trial at a leading university medical center in the United States, where COVID-19 continues to have a devastating impact on the lives of patients and their families.”

About COVID-19-Associated Acute Respiratory Distress Syndrome

ARDS is a dangerous, potentially fatal respiratory condition in which the lungs acquire a widespread injury that reduces their ability to provide the body with enough oxygen. The condition causes fluid buildup in the lungs, which in turn decreases blood oxygen to critically low levels. ARDS is a medical emergency,⁶ and a major complication in severe cases of COVID-19, affecting 42% of patients presenting with COVID-19 pneumonia and 61–81% of those requiring intensive care.⁷

ARDS also triggers an adverse immune response, causing a release of cytokines, a type of small protein that can cause inflammation in the lungs and other organs. This inflammation, in combination with low levels of blood oxygen, can lead to such life-threatening problems as organ failure and sometimes multiple organ failure. Certain risk factors increase the likelihood of the development of ARDS in people with COVID-19, including advanced age, diabetes, a history of cardiac disease and high blood pressure.⁶

About EOM613

EOM613 is an investigational, first-in-class, dual-acting, broad-spectrum immunomodulator designed to provide both an anti-inflammatory effect at the site of cytokine and chemokine overactivity, and a pro-inflammatory effect, when needed. EOM613 is designed to counteract the most severe inflammatory effects of viruses, such as cytokine storm or hyperimmune response following infection with the novel coronavirus that causes COVID-19, autoimmune attacks that cause joint damage and pain associated with rheumatoid arthritis, and cytokine- and chemokine-related body-wasting syndromes such as cachexia. By re-establishing balance, EOM613 may rescue, repair, and restore an immune system that has been confronted by an invading antigen, pathogen, or virus. This dual-acting, broad-spectrum approach may overcome a key limitation of conventional immunomodulators. It is administered as a subcutaneous injection, unlike conventional immunomodulators which often require intravenous infusion. EOM613 has already demonstrated clinical improvements in various disease states and immune-related biomarkers and general tolerability across five Phase 2 clinical trials in patients with cachexia associated with AIDS and cancer, and in patients with rheumatoid arthritis. EOM613 is efficiently manufactured from readily available materials.

About EOM Pharmaceuticals

EOM Pharmaceuticals is a privately held, clinical-stage pharmaceutical company with a pipeline of products that have already shown clinical relevance in multiple Phase 2 clinical trials. The Company’s mission is to pursue innovative approaches with novel types of small molecule therapeutics to solve the problems of some of today’s most urgent and unmet medical needs. EOM’s pipeline is built on proprietary innovations designed to rescue, repair, and restore health. These innovations include the development of the first-and-only dual-acting, broad-spectrum immunomodulator EOM613, which has the potential to treat systemic illness due to an intense inflammatory immune reaction, including COVID-19, influenza, and cancer cachexia, and its advanced formulation of EOM147, the first potential topically administered eye drop to treat retinal diseases. Multiple Phase 2 trials suggest EOM613 and EOM147 have improved relevant clinical measures and are well tolerated. For more information about EOM Pharmaceuticals, please visit www.eompharma.com.

*EOM613 has had other names, including Product R, OHR118, AVR118, and OHR/AVR118.

Forward-Looking Statements

This press release may contain forward-looking statements as such term is understood in the federal securities laws, including, among others, statements regarding the potential to develop a COVID-19 therapy. Actual results may differ materially from those set forth in this press release due to the risks and uncertainties inherent in drug research and development. Any forward-looking statements in this press release speak only as of the date of this press release, and EOM Pharmaceuticals, Inc. undertakes no obligation to update or revise the statements in the future, even if new information becomes available.

¹ Levett PN, Hirschman SZ, Roach TC, Broome H, Alexander RJ, Fraser HS. Randomized, placebo-controlled trial of product R, a peptide-nucleic acid immunomodulator, in the treatment of adults infected with HIV. HIV Clin Trials. 2002 Jul-Aug;3(4):272-8. doi: 10.1310/N34A-653T-ABF5-8Q1R. PMID: 12187500.

² D’Olimpio JT, Hirschman SZ, Shtemer Z, Didiego M. Anti-cachectic effects of a novel peptide nucleic acid: Preliminary results of a phase I/II clinical trial. DOI: 10.1200/jco.2004.22.90140.8087 (presentation abstract). Journal of Clinical Oncology. July 15, 2004; 22, no. 14_suppl 8087-8087.

³ D’Olimpio JT, Chasen MR, Sharma R, Diego M, Gullo V, MacDonald N. Phase II study of AVR118 in the management of cancer related anorexia/cachexia. DOI: 10.1200/jco.2009.27.15_suppl.e20631 (presentation abstract). Journal of Clinical Oncology 2009; 27, no. 15_suppl., e20631-e20631.

⁴ Chasen M, Hirschman SZ, Bhargava R. Phase II study of the novel peptide-nucleic acid OHR118 in the management of cancer-related anorexia/cachexia. J Am Med Dir Assoc. 2011 Jan;12(1):62-7. doi: 10.1016/j.jamda.2010.02.012. Epub 2010 May 15. PMID: 21194662.

⁵ Chasen M, Bhargava R, Hirschman SZ, Taraporewala IB. A Phase II study of OHR/AVR118 in anorexia-cachexia. Poster presentation at: the 7th Cachexia conference, Kobe/Osaka, Japan, December 9-11, 2013.

⁶ Yale Medicine. Fact Sheets: Acute Respiratory Distress Syndrome (ARDS). Available at: https://www.yalemedicine.org/conditions/ards. Accessed December 23, 2020.|

⁷ Gibson PG, Qin L, Puah SH. COVID-19 acute respiratory distress syndrome (ARDS): clinical features and differences from typical pre-COVID-19 ARDS. Med J Aust. 2020;213(2):54-56.e1. doi:10.5694/mja2.50674

Contacts

INVESTOR RELATIONS:

Eli Goldberger

EOM Pharmaceuticals

elig@eompharma.com
201.351.0605, ext. 2

MEDIA:

Dawn Maniglia

TogoRun

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917.862.5444