Category: BMY

BMY – U.S. Food and Drug Administration Accepts for Priority Review Bristol Myers Squibb's Application for Orencia (abatacept) for the Prevention of Acute Graft Versus Host Disease (aGvHD)

PRINCETON, N.J.–()–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 Orencia (abatacept) for the prevention of moderate to severe acute graft versus host disease (aGvHD) in patients 6 years of age and older receiving unrelated donor hematopoietic stem cell transplantation (HSCT). The FDA granted the application Priority Review and assigned a Prescription Drug User Fee Act (PDUFA) goal date of December 23, 2021.

“While stem cell transplants are an effective treatment for aggressive leukemias and other hematological malignancies, patients who receive stem cell transplants from unrelated and human leukocyte antigens (HLA)-mismatched donors are at high risk for developing aGvHD,” said study lead investigator Leslie Kean, M.D., PhD, Director of the Pediatric Stem Cell Transplantation Program, Boston Children’s Hospital/Dana-Farber Cancer Institute. “There is a tremendous need to expand the stem cell donor pool by lowering the risk of aGvHD in both adults and children receiving unrelated donor stem cell transplants.”

Stem cell transplants include infusion of donor T-cells, a type of white blood cell that recognizes and destroys foreign invaders in the recipient’s body, including cancer cells. GvHD occurs when the donor T-cells also recognize the patient’s healthy cells as foreign and start attacking healthy tissues and organs. To initiate this attack, T-cells require activation through a signaling process called co-stimulation. Between 30 and 70 percent of transplant recipients develop aGvHD, depending on donor type, transplant technique, and other features. Orencia, a therapy currently approved to treat various arthritic conditions, binds to and inhibits protein targets involved in co-stimulation, thus inhibiting T-cell activation.

“For patients who receive unrelated donor stem cell transplants, in particular for racial and ethnic minority patient populations, there is a heightened risk of developing aGvHD, a potentially life-threatening medical complication for which there are no approved preventive therapies,” said Mary Beth Harler, M.D., head of Immunology and Fibrosis Development, Bristol Myers Squibb. “We look forward to working with the FDA to bring Orencia to this new patient population and employ pathbreaking science in an effort to address unmet needs of underserved patients.”

The sBLA submitted to the FDA is based on results from the Phase 2 ABA2 trial and a registry trial based on real world evidence. The ABA2 trial assessed the impact of Orencia on the prevention of severe aGvHD, when added to a standard GvHD prophylactic regimen administered to patients with hematologic malignancies receiving a stem cell transplant from an unrelated, HLA-matched or mismatched donor. A mismatch in HLA increases the risk of GvHD. Results from ABA2 showed that treatment with Orencia resulted in a significant reduction in severe aGvHD and associated morbidity without an increase in disease relapse. The findings of the real-world analysis were consistent with those of ABA2.

Bristol Myers Squibb thanks the patients and investigators who participated in this clinical trial.

About ABA2

The ABA2 study was a multicenter, Phase 2 investigator sponsored trial conducted by Dr. Leslie Kean of Boston Children’s Hospital/Dana Farber Cancer Institute. ABA2 had two cohorts: a single arm cohort for patients receiving transplants from mismatched unrelated donors (MMUD) (“7/8” cohort), and a randomized, double blind, placebo-controlled cohort for patients receiving transplants from 8/8 matched unrelated donors (MUD) (“8/8” cohort). All subjects received a calcineurin inhibitor (CNI), with dosing starting on day -2 and continuing through at least Day 100 as tolerated, and methotrexate (MTX) on days one, three, six and 11 (transplant day is Day 0). Orencia-treated subjects received 10 mg/kg Orencia on days -1, 5, 14 and 28.

In the ABA2 clinical trial, addition of Orencia to SOC aGvHD prophylaxis of MTX+CNI resulted in a significantly higher aGvHD-free survival (GFS) rate compared to registry controls in the single-arm 7/8 HLA-matched cohort, and numerically higher severe GFS rate in the double-blind, placebo-controlled 8/8 HLA-matched cohort at 180 days post-transplant.

About Acute Graft Versus Host Disease and Impact on a Diverse Patient Population

Graft versus host disease (GvHD) after a hematopoietic stem cell transplant occurs when transplanted donor T-cells recognize antigenic differences between the donor and the recipient, and attack the recipient’s healthy tissue and organs. Acute graft versus-host disease (aGvHD) impacts between 30 and 70 percent of patients, depending on donor type, transplant technique, and other features, with racial and ethnic minority patient populations more likely to experience challenges following a hematopoietic stem cell transplantation. This may be due to several factors that impact overall outcome, including a lack of donor availability and related care. This activation of T-cells can result in severe immune-mediated tissue damage to the host, with the skin, liver and gastrointestinal tract being the most common targets. aGvHD-mediated damage to these vital organs has been associated with increased morbidity and death.

HSCT is an effective treatment for aggressive leukemias and other hematological malignancies, often representing the only option for cure. However, some of its benefit, especially in the case of unrelated donor transplantation, is offset by a high rate of transplant-related mortality (TRM) stemming largely from severe aGvHD and infection.

About ORENCIA®

ORENCIA® is an immunomodulator that disrupts the continuous cycle of T-cell activation.

U.S. Indications/Usage and Important Safety Information for ORENCIA® (abatacept)

Indications and Usage

Adult Rheumatoid Arthritis: ORENCIA® (abatacept) is indicated for the treatment of adult patients with moderately to severely active rheumatoid arthritis (RA).

Polyarticular Juvenile Idiopathic Arthritis: ORENCIA® (abatacept) is indicated for the treatment of patients 2 years of age and older with moderately to severely active polyarticular juvenile idiopathic arthritis (pJIA).

Adult Psoriatic Arthritis: ORENCIA® (abatacept) is indicated for the treatment of adult patients with active psoriatic arthritis (PsA).

Limitations of Use: The concomitant use of ORENCIA with other potent immunosuppressants [e.g., biologic disease-modifying antirheumatic drugs (bDMARDS), Janus kinase (JAK) inhibitors] is not recommended.

Important Safety Information for ORENCIA® (abatacept)

Concomitant Use with TNF Antagonists, Other Biologic RA/PsA Therapy, or JAK Inhibitors: Concurrent therapy with ORENCIA and a TNF antagonist is not recommended. In controlled clinical trials, adult RA patients receiving concomitant intravenous ORENCIA and TNF antagonist therapy experienced more infections (63% vs 43%) and serious infections (4.4% vs 0.8%) compared to patients treated with only TNF antagonists, without an important enhancement of efficacy. Additionally, concomitant use of ORENCIA with other biologic RA/PsA therapy or JAK inhibitors is not recommended.

Hypersensitivity: There were 2 cases (<0.1%; n=2688) of anaphylaxis reactions in clinical trials with adult RA patients treated with intravenous ORENCIA. Other reactions potentially associated with drug hypersensitivity, such as hypotension, urticaria, and dyspnea, each occurred in <0.9% of patients. There was one case of a hypersensitivity reaction with ORENCIA in pJIA clinical trials (0.5%; n=190). In post marketing experience, fatal anaphylaxis following the first infusion of ORENCIA and life-threatening cases of angioedema have been reported. Angioedema has occurred as early as after the first dose of ORENCIA, but also has occurred with subsequent doses. Angioedema reactions have occurred within hours of administration and in some instances had a delayed onset (i.e., days). Appropriate medical support measures for treating hypersensitivity reactions should be available for immediate use. If an anaphylactic or other serious allergic reaction occurs, administration of intravenous or subcutaneous ORENCIA should be stopped immediately and permanently discontinued, with appropriate therapy instituted.

Infections: Serious infections, including sepsis and pneumonia, were reported in 3% and 1.9% of RA patients treated with intravenous ORENCIA and placebo, respectively. Some of these infections have been fatal. Many of the serious infections have occurred in patients on concomitant immunosuppressive therapy which, in addition to their underlying disease, could further predispose them to infection. Caution should be exercised in patients with a history of infection or underlying conditions which may predispose them to infections. Treatment with ORENCIA should be discontinued if a patient develops a serious infection. Patients should be screened for tuberculosis and viral hepatitis in accordance with published guidelines, and if positive, treated according to standard medical practice prior to therapy with ORENCIA.

Immunizations: Prior to initiating ORENCIA in pediatric and adult patients, update vaccinations in accordance with current vaccination guidelines. Live vaccines should not be given concurrently with ORENCIA or within 3 months after discontinuation. ORENCIA may blunt the effectiveness of some immunizations.

Use in Patients with Chronic Obstructive Pulmonary Disease (COPD): In Study V, adult COPD patients treated with ORENCIA for RA developed adverse events more frequently than those treated with placebo (97% vs 88%, respectively). Respiratory disorders occurred more frequently in patients treated with ORENCIA compared to those on placebo (43% vs 24%, respectively), including COPD exacerbation, cough, rhonchi, and dyspnea. A greater percentage of patients treated with ORENCIA developed a serious adverse event compared to those on placebo (27% vs 6%), including COPD exacerbation [3 of 37 patients (8%)] and pneumonia [1 of 37 patients (3%)]. Use of ORENCIA in patients with COPD should be undertaken with caution, and such patients monitored for worsening of their respiratory status.

Immunosuppression: In clinical trials in adult RA patients, a higher rate of infections was seen in ORENCIA-treated patients compared to placebo-treated patients. The impact of treatment with ORENCIA on the development and course of malignancies is not fully understood. There have been reports of malignancies, including skin cancer in patients receiving ORENCIA. Periodic skin examinations are recommended for all ORENCIA-treated patients, particularly those with risk factors for skin cancer.

Blood Glucose Testing: ORENCIA for intravenous administration contains maltose, which may result in falsely elevated blood glucose readings on the day of infusion when using blood glucose monitors with test strips utilizing glucose dehydrogenase pyrroloquinoline quinone (GDH-PQQ). Consider using monitors and advising patients to use monitors that do not react with maltose, such as those based on glucose dehydrogenase nicotine adenine dinucleotide (GDH-NAD), glucose oxidase or glucose hexokinase test methods. ORENCIA for subcutaneous (SC) administration does not contain maltose; therefore, patients do not need to alter their glucose monitoring.

Pregnancy: There are no adequate and well-controlled studies of ORENCIA use in pregnant women and the data with ORENCIA use in pregnant women are insufficient to inform on drug-associated risk. A pregnancy registry has been established to monitor pregnancy outcomes in women exposed to ORENCIA during pregnancy. Healthcare professionals are encouraged to register patients by calling 1-877-311-8972.

Lactation: There is no information regarding the presence of abatacept in human milk, the effects on the breastfed infant, or the effects on milk production. However, abatacept was present in the milk of lactating rats dosed with abatacept.

Most Serious Adverse Reactions: Serious infections (3% ORENCIA vs 1.9% placebo) and malignancies (1.3% ORENCIA vs 1.1% placebo).

Malignancies: The overall frequency of malignancies was similar between adult RA patients treated with ORENCIA or placebo. However, more cases of lung cancer were observed in patients treated with ORENCIA (0.2%) than those on placebo (0%). A higher rate of lymphoma was seen compared to the general population; however, patients with RA, particularly those with highly active disease, are at a higher risk for the development of lymphoma. The potential role of ORENCIA in the development of malignancies in humans is unknown.

Most Frequent Adverse Events (≥10%): Headache, upper respiratory tract infection, nasopharyngitis, and nausea were the most commonly reported adverse events in the adult RA clinical studies. Other events reported in ≥5% of pJIA patients were diarrhea, cough, pyrexia, and abdominal pain. In general, the adverse events in pediatric pJIA and adult PsA patients were similar in frequency and type to those seen in adult RA patients.

Note concerning ORENCIA administration options: ORENCIA may be administered as an intravenous infusion only for patients 6 years of age and older. PJIA patients may self-inject with ORENCIA or the patient’s caregiver may administer ORENCIA if both the healthcare practitioner and the parent/legal guardian determines it is appropriate. The ability of pediatric patients to self-inject with the autoinjector has not been tested.

Please click here for Full Prescribing Information.

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 Orencia (abatacept) may not receive regulatory approval for the additional indication described in this release in the currently anticipated timeline or at all 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. It should also be noted that a Priority Review designation does not change the standards for FDA approval. 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, 2020, 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.

corporatefinancial-news

BMY – EMA Validates Bristol Myers Squibb's Applications for Opdivo (nivolumab) + Yervoy (ipilimumab) and Opdivo + Chemotherapy as First-Line Treatments for Unresectable Advanced, Recurrent or Metastatic Esophageal Squamous Cell Carcinoma

PRINCETON, N.J.–()–Bristol Myers Squibb (NYSE: BMY) today announced that the European Medicines Agency (EMA) has validated its Type II Variation Marketing Authorization Applications (MAA) for both Opdivo (nivolumab) in combination with Yervoy (ipilimumab) and Opdivo in combination with fluoropyrimidine- and platinum-containing chemotherapy as first-line treatments for adult patients with unresectable advanced, recurrent or metastatic esophageal squamous cell carcinoma (ESCC). Validation of these applications confirm that the submissions are complete and begins the EMA’s centralized review process.

“Outcomes for patients with advanced esophageal squamous cell carcinoma treated with chemotherapy alone remain poor, and there is a clear need for additional options beyond this long-standing standard of care,” said Ian M. Waxman, M.D., development lead, gastrointestinal cancers, Bristol Myers Squibb. “The validation of our applications moves us a step closer to potentially bringing these two Opdivo-based regimens to patients in the EU who may benefit.”

The applications are based on results from the pivotal Phase 3 CheckMate -648 trial, in which both Opdivo-based treatment combinations — Opdivo plus Yervoy and Opdivo plus chemotherapy — demonstrated a statistically significant and clinically meaningful overall survival (OS) benefit compared to chemotherapy at the pre-specified interim analysis in patients with unresectable advanced or metastatic esophageal squamous cell carcinoma (ESCC) with tumor cell PD-L1 expression ≥1%, as well as in the all-randomized population. Opdivo plus Yervoy is the first dual immunotherapy combination to demonstrate a superior survival benefit versus chemotherapy in this setting. The safety profiles of Opdivo and chemotherapy and of Opdivo plus Yervoy were consistent with the known safety profiles of the individual components.

Results from CheckMate -648 were presented in an oral session during the 2021 American Society of Clinical Oncology (ASCO) Annual Meeting and were selected for the official ASCO press program.

Bristol Myers Squibb thanks the patients and investigators involved in the CheckMate -648 trial.

About CheckMate -648

CheckMate -648 is a randomized Phase 3 study evaluating Opdivo plus Yervoy or Opdivo plus fluorouracil and cisplatin against fluorouracil plus cisplatin alone in patients with unresectable advanced or metastatic esophageal squamous cell carcinoma. The primary endpoints of the trial are overall survival (OS) and progression-free survival (PFS) by blinded independent central review (BICR) in patients whose tumors express PD-L1 ≥1% for both Opdivo-based combinations versus chemotherapy. Secondary endpoints of the trial include OS and PFS by BICR in the all-randomized population.

In the Opdivo plus Yervoy arm, patients received treatment with Opdivo 3 mg/kg every 2 weeks and Yervoy 1 mg/kg every 6 weeks up to 24 months or until disease progression or unacceptable toxicity. In the Opdivo plus chemotherapy arm, patients received treatment with Opdivo 240 mg on Day 1 and Day 15, fluorouracil 800 mg/m²/day on Day 1 through Day 5 (for 5 days), and cisplatin 80 mg/m² on Day 1 of four-week cycle. Patients received Opdivo for up to 24 months or until disease progression or unacceptable toxicity, and chemotherapy until disease progression or unacceptable toxicity.

About Esophageal Cancer

Esophageal cancer is the eighth most common cancer and the sixth leading cause of death from cancer worldwide, with approximately 600,000 new cases and over 540,000 deaths in 2020. The two most common types of esophageal cancer are squamous cell carcinoma and adenocarcinoma, which account for approximately 85% and 15% of all esophageal cancers, respectively, though esophageal tumor histology can vary by region with the highest rate of esophageal squamous cell carcinoma occurring in Asia (~95%), Europe (~65%) and North America (35%).

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

Bristol Myers Squibb is inspired by a single vision — transforming patients’ 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.

About Yervoy

Yervoy is a recombinant, human monoclonal antibody that binds to the cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4). CTLA-4 is a negative regulator of T-cell activity. Yervoy binds to CTLA-4 and blocks the interaction of CTLA-4 with its ligands, CD80/CD86. Blockade of CTLA-4 has been shown to augment T-cell activation and proliferation, including the activation and proliferation of tumor infiltrating T-effector cells. Inhibition of CTLA-4 signaling can also reduce T-regulatory cell function, which may contribute to a general increase in T-cell responsiveness, including the anti-tumor immune response. On March 25, 2011, the U.S. Food and Drug Administration (FDA) approved Yervoy 3 mg/kg monotherapy for patients with unresectable or metastatic melanoma. Yervoy is approved for unresectable or metastatic melanoma in more than 50 countries. There is a broad, ongoing development program in place for Yervoy spanning multiple tumor types.

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

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

OPDIVO® (nivolumab), in combination with cabozantinib, is indicated for the first-line treatment of patients with advanced renal cell carcinoma (RCC).

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

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), 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.

OPDIVO® (nivolumab) is indicated for the adjuvant treatment of completely resected esophageal or gastroesophageal junction cancer with residual pathologic disease in patients who have received neoadjuvant chemoradiotherapy (CRT).

OPDIVO® (nivolumab), in combination with fluoropyrimidine- and platinum-containing chemotherapy, is indicated for the treatment of patients with advanced or metastatic gastric cancer, gastroesophageal junction cancer, and esophageal adenocarcinoma.

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 patients receiving OPDIVO 1 mg/kg with YERVOY 3 mg/kg every 3 weeks, immune-mediated pneumonitis occurred in 7% (31/456) of patients, including Grade 4 (0.2%), Grade 3 (2.0%), and Grade 2 (4.4%). 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.

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

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%).

Immune-Mediated Hepatitis and Hepatotoxicity

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%).

OPDIVO in combination with cabozantinib can cause hepatic toxicity with higher frequencies of Grade 3 and 4 ALT and AST elevations compared to OPDIVO alone. Consider more frequent monitoring of liver enzymes as compared to when the drugs are administered as single agents. In patients receiving OPDIVO and cabozantinib, Grades 3 and 4 increased ALT or AST were seen in 11% of patients.

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 and cabozantinib, adrenal insufficiency occurred in 4.7% (15/320) of patients, including Grade 3 (2.2%) and Grade 2 (1.9%).

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%).

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%).

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 inflammatory toxicities can occur; gastrointestinal: pancreatitis to include increases in serum amylase and lipase levels, gastritis, duodenitis; musculoskeletal and connective tissue: myositis/polymyositis, rhabdomyolysis, and associated sequelae including renal failure, arthritis, polymyalgia rheumatica; endocrine: hypoparathyroidism; other (hematologic/immune): hemolytic anemia, aplastic anemia, hemophagocytic lymphohistiocytosis (HLH), systemic inflammatory response syndrome, histiocytic necrotizing lymphadenitis (Kikuchi lymphadenitis), sarcoidosis, immune thrombocytopenic purpura, solid organ transplant rejection.

In addition to the immune-mediated adverse reactions listed above, across clinical trials of YERVOY monotherapy or in combination with OPDIVO, the following clinically significant immune-mediated adverse reactions, some with fatal outcome, occurred in <1% of patients unless otherwise specified: nervous system: autoimmune neuropathy (2%), myasthenic syndrome/myasthenia gravis, motor dysfunction; cardiovascular: angiopathy, temporal arteritis; ocular: blepharitis, episcleritis, orbital myositis, scleritis; gastrointestinal: pancreatitis (1.3%); other (hematologic/immune): conjunctivitis, cytopenias (2.5%), eosinophilia (2.1%), erythema multiforme, hypersensitivity vasculitis, neurosensory hypoacusis, psoriasis.

Some ocular IMAR cases can be associated with retinal detachment. Various grades of visual impairment, including blindness, can occur. If uveitis occurs in combination with other immune-mediated adverse reactions, consider a Vogt-Koyanagi-Harada–like syndrome, which has been observed in patients receiving OPDIVO and YERVOY, as this may require treatment with systemic corticosteroids to reduce the risk of permanent vision loss.

Infusion-Related Reactions

OPDIVO and YERVOY can cause severe infusion-related reactions. Discontinue OPDIVO and YERVOY in patients with severe (Grade 3) or life-threatening (Grade 4) infusion-related reactions. Interrupt or slow the rate of infusion in patients with mild (Grade 1) or moderate (Grade 2) infusion-related reactions. In patients receiving OPDIVO monotherapy as a 60-minute infusion, infusion-related reactions occurred in 6.4% (127/1994) of patients. In a separate trial in which patients received OPDIVO monotherapy as a 60-minute infusion or a 30-minute infusion, infusion-related reactions occurred in 2.2% (8/368) and 2.7% (10/369) of patients, respectively. Additionally, 0.5% (2/368) and 1.4% (5/369) of patients, respectively, experienced adverse reactions within 48 hours of infusion that led to dose delay, permanent discontinuation or withholding of OPDIVO. In melanoma patients receiving OPDIVO 1 mg/kg with YERVOY 3 mg/kg every 3 weeks, infusion-related reactions occurred in 2.5% (10/407) of patients. In HCC patients receiving OPDIVO 1 mg/kg with YERVOY 3 mg/kg every 3 weeks, infusion-related reactions occurred in 8% (4/49) of patients. In RCC patients receiving OPDIVO 3 mg/kg with YERVOY 1 mg/kg, infusion-related reactions occurred in 5.1% (28/547) of patients. In MSI-H/dMMR mCRC patients receiving OPDIVO 3 mg/kg with YERVOY 1 mg/kg every 3 weeks, infusion-related reactions occurred in 4.2% (5/119) of patients. In MPM patients receiving OPDIVO 3 mg/kg every 2 weeks with YERVOY 1 mg/kg every 6 weeks, infusion-related reactions occurred in 12% (37/300) of patients.

Complications of Allogeneic Hematopoietic Stem Cell Transplantation

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

Follow patients closely for evidence of transplant-related complications and intervene promptly. Consider the benefit versus risks of treatment with OPDIVO and YERVOY prior to or after an allogeneic HSCT.

Embryo-Fetal Toxicity

Based on its mechanism of action and findings from animal studies, OPDIVO and YERVOY can cause fetal harm when administered to a pregnant woman. The effects of YERVOY are likely to be greater during the second and third trimesters of pregnancy. Advise pregnant women of the potential risk to a fetus. Advise females of reproductive potential to use effective contraception during treatment with OPDIVO and YERVOY and for at least 5 months after the last dose.

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

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

Lactation

There are no data on the presence of OPDIVO or YERVOY in human milk, the effects on the breastfed child, or the effects on milk production. Because of the potential for serious adverse reactions in breastfed children, advise women not to breastfeed during treatment and for 5 months after the last dose.

Serious Adverse Reactions

In Checkmate 037, serious adverse reactions occurred in 41% of patients receiving OPDIVO (n=268). Grade 3 and 4 adverse reactions occurred in 42% of patients receiving OPDIVO. The most frequent Grade 3 and 4 adverse drug reactions reported in 2% to <5% of patients receiving OPDIVO were abdominal pain, hyponatremia, increased aspartate aminotransferase, and increased lipase. In Checkmate 066, serious adverse reactions occurred in 36% of patients receiving OPDIVO (n=206). Grade 3 and 4 adverse reactions occurred in 41% of patients receiving OPDIVO. The most frequent Grade 3 and 4 adverse reactions reported in ≥2% of patients receiving OPDIVO were gamma-glutamyltransferase increase (3.9%) and diarrhea (3.4%). In Checkmate 067, serious adverse reactions (74% and 44%), adverse reactions leading to permanent discontinuation (47% and 18%) or to dosing delays (58% and 36%), and Grade 3 or 4 adverse reactions (72% and 51%) all occurred more frequently in the OPDIVO plus YERVOY arm (n=313) relative to the OPDIVO arm (n=313). The most frequent (≥10%) serious adverse reactions in the OPDIVO plus YERVOY arm and the OPDIVO arm, respectively, were diarrhea (13% and 2.2%), colitis (10% and 1.9%), and pyrexia (10% and 1.0%). In Checkmate 227, serious adverse reactions occurred in 58% of patients (n=576). The most frequent (≥2%) serious adverse reactions were pneumonia, diarrhea/colitis, pneumonitis, hepatitis, pulmonary embolism, adrenal insufficiency, and hypophysitis. Fatal adverse reactions occurred in 1.7% of patients; these included events of pneumonitis (4 patients), myocarditis, acute kidney injury, shock, hyperglycemia, multi-system organ failure, and renal failure. In Checkmate 9LA, serious adverse reactions occurred in 57% of patients (n=358). The most frequent (>2%) serious adverse reactions were pneumonia, diarrhea, febrile neutropenia, anemia, acute kidney injury, musculoskeletal pain, dyspnea, pneumonitis, and respiratory failure. Fatal adverse reactions occurred in 7 (2%) patients, and included hepatic toxicity, acute renal failure, sepsis, pneumonitis, diarrhea with hypokalemia, and massive hemoptysis in the setting of thrombocytopenia. In Checkmate 017 and 057, serious adverse reactions occurred in 46% of patients receiving OPDIVO (n=418). The most frequent serious adverse reactions reported in ≥2% of patients receiving OPDIVO were pneumonia, pulmonary embolism, dyspnea, pyrexia, pleural effusion, pneumonitis, and respiratory failure. In Checkmate 057, fatal adverse reactions occurred; these included events of infection (7 patients, including one case of Pneumocystis jirovecii pneumonia), pulmonary embolism (4 patients), and limbic encephalitis (1 patient). In Checkmate 743, serious adverse reactions occurred in 54% of patients receiving OPDIVO plus YERVOY. The most frequent serious adverse reactions reported in ≥2% of patients were pneumonia, pyrexia, diarrhea, pneumonitis, pleural effusion, dyspnea, acute kidney injury, infusion-related reaction, musculoskeletal pain, and pulmonary embolism. Fatal adverse reactions occurred in 4 (1.3%) patients and included pneumonitis, acute heart failure, sepsis, and encephalitis. In Checkmate 214, serious adverse reactions occurred in 59% of patients receiving OPDIVO plus YERVOY (n=547). The most frequent serious adverse reactions reported in ≥2% of patients were diarrhea, pyrexia, pneumonia, pneumonitis, hypophysitis, acute kidney injury, dyspnea, adrenal insufficiency, and colitis. In Checkmate 9ER, serious adverse reactions occurred in 48% of patients receiving OPDIVO and cabozantinib (n=320). The most frequent serious adverse reactions reported in ≥2% of patients were diarrhea, pneumonia, pneumonitis, pulmonary embolism, urinary tract infection, and hyponatremia. Fatal intestinal perforations occurred in 3 (0.9%) patients. In Checkmate 025, serious adverse reactions occurred in 47% of patients receiving OPDIVO (n=406). The most frequent serious adverse reactions reported in ≥2% of patients were acute kidney injury, pleural effusion, pneumonia, diarrhea, and hypercalcemia. In Checkmate 205 and 039, adverse reactions leading to discontinuation occurred in 7% and dose delays due to adverse reactions occurred in 34% of patients (n=266). Serious adverse reactions occurred in 26% of patients. The most frequent serious adverse reactions reported in ≥1% of patients were pneumonia, infusion-related reaction, pyrexia, colitis or diarrhea, pleural effusion, pneumonitis, and rash. Eleven patients died from causes other than disease progression: 3 from adverse reactions within 30 days of the last OPDIVO dose, 2 from infection 8 to 9 months after completing OPDIVO, and 6 from complications of allogeneic HSCT. In Checkmate 141, serious adverse reactions occurred in 49% of patients receiving OPDIVO (n=236). The most frequent serious adverse reactions reported in ≥2% of patients receiving OPDIVO were pneumonia, dyspnea, respiratory failure, respiratory tract infection, and sepsis. In Checkmate 275, serious adverse reactions occurred in 54% of patients receiving OPDIVO (n=270). The most frequent serious adverse reactions reported in ≥2% of patients receiving OPDIVO were urinary tract infection, sepsis, diarrhea, small intestine obstruction, and general physical health deterioration. In Checkmate 142 in MSI-H/dMMR mCRC patients receiving OPDIVO with YERVOY (n=119), serious adverse reactions occurred in 47% of patients. The most frequent serious adverse reactions reported in ≥2% of patients were colitis/diarrhea, hepatic events, abdominal pain, acute kidney injury, pyrexia, and dehydration. In Checkmate 040, serious adverse reactions occurred in 59% of patients receiving OPDIVO with YERVOY (n=49). Serious adverse reactions reported in ≥4% of patients were pyrexia, diarrhea, anemia, increased AST, adrenal insufficiency, ascites, esophageal varices hemorrhage, hyponatremia, increased blood bilirubin, and pneumonitis. In Checkmate 238, serious adverse reactions occurred in 18% of patients receiving OPDIVO (n=452). Grade 3 or 4 adverse reactions occurred in 25% of OPDIVO-treated patients (n=452). The most frequent Grade 3 and 4 adverse reactions reported in ≥2% of OPDIVO-treated patients were diarrhea and increased lipase and amylase. In Attraction-3, serious adverse reactions occurred in 38% of patients receiving OPDIVO (n=209). Serious adverse reactions reported in ≥2% of patients who received OPDIVO were pneumonia, esophageal fistula, interstitial lung disease, and pyrexia. The following fatal adverse reactions occurred in patients who received OPDIVO: interstitial lung disease or pneumonitis (1.4%), pneumonia (1.0%), septic shock (0.5%), esophageal fistula (0.5%), gastrointestinal hemorrhage (0.5%), pulmonary embolism (0.5%), and sudden death (0.5%). In Checkmate 577, serious adverse reactions occurred in 33% of patients receiving OPDIVO (n=532). A serious adverse reaction reported in ≥2% of patients who received OPDIVO was pneumonitis. A fatal reaction of myocardial infarction occurred in one patient who received OPDIVO. In Checkmate 649, serious adverse reactions occurred in 52% of patients treated with OPDIVO in combination with chemotherapy (n=782). The most frequent serious adverse reactions reported in ≥ 2% of patients treated with OPDIVO in combination with chemotherapy were vomiting (3.7%), pneumonia (3.6%), anemia (3.6%), pyrexia (2.8%), diarrhea (2.7%), febrile neutropenia (2.6%), and pneumonitis (2.4%). Fatal adverse reactions occurred in 16 (2.0%) patients who were treated with OPDIVO in combination with chemotherapy; these included pneumonitis (4 patients), febrile neutropenia (2 patients), stroke (2 patients), gastrointestinal toxicity, intestinal mucositis, septic shock, pneumonia, infection, gastrointestinal bleeding, mesenteric vessel thrombosis, and disseminated intravascular coagulation.

Common Adverse Reactions

In Checkmate 037, the most common adverse reaction (≥20%) reported with OPDIVO (n=268) was rash (21%). In Checkmate 066, the most common adverse reactions (≥20%) reported with OPDIVO (n=206) vs dacarbazine (n=205) were fatigue (49% vs 39%), musculoskeletal pain (32% vs 25%), rash (28% vs 12%), and pruritus (23% vs 12%). In Checkmate 067, the most common (≥20%) adverse reactions in the OPDIVO plus YERVOY arm (n=313) were fatigue (62%), diarrhea (54%), rash (53%), nausea (44%), pyrexia (40%), pruritus (39%), musculoskeletal pain (32%), vomiting (31%), decreased appetite (29%), cough (27%), headache (26%), dyspnea (24%), upper respiratory tract infection (23%), arthralgia (21%), and increased transaminases (25%). In Checkmate 067, the most common (≥20%) adverse reactions in the OPDIVO arm (n=313) were fatigue (59%), rash (40%), musculoskeletal pain (42%), diarrhea (36%), nausea (30%), cough (28%), pruritus (27%), upper respiratory tract infection (22%), decreased appetite (22%), headache (22%), constipation (21%), arthralgia (21%), and vomiting (20%). In Checkmate 227, the most common (≥20%) adverse reactions were fatigue (44%), rash (34%), decreased appetite (31%), musculoskeletal pain (27%), diarrhea/colitis (26%), dyspnea (26%), cough (23%), hepatitis (21%), nausea (21%), and pruritus (21%). In Checkmate 9LA, the most common (>20%) adverse reactions were fatigue (49%), musculoskeletal pain (39%), nausea (32%), diarrhea (31%), rash (30%), decreased appetite (28%), constipation (21%), and pruritus (21%). In Checkmate 017 and 057, the most common adverse reactions (≥20%) in patients receiving OPDIVO (n=418) were fatigue, musculoskeletal pain, cough, dyspnea, and decreased appetite. In Checkmate 743, the most common adverse reactions (≥20%) in patients receiving OPDIVO plus YERVOY were fatigue (43%), musculoskeletal pain (38%), rash (34%), diarrhea (32%), dyspnea (27%), nausea (24%), decreased appetite (24%), cough (23%), and pruritus (21%). In Checkmate 214, the most common adverse reactions (≥20%) reported in patients treated with OPDIVO plus YERVOY (n=547) were fatigue (58%), rash (39%), diarrhea (38%), musculoskeletal pain (37%), pruritus (33%), nausea (30%), cough (28%), pyrexia (25%), arthralgia (23%), decreased appetite (21%), dyspnea (20%), and vomiting (20%). In Checkmate 9ER, the most common adverse reactions (≥20%) in patients receiving OPDIVO and cabozantinib (n=320) were diarrhea (64%), fatigue (51%), hepatotoxicity (44%), palmar-plantar erythrodysaesthesia syndrome (40%), stomatitis (37%), rash (36%), hypertension (36%), hypothyroidism (34%), musculoskeletal pain (33%), decreased appetite (28%), nausea (27%), dysgeusia (24%), abdominal pain (22%), cough (20%) and upper respiratory tract infection (20%). In Checkmate 025, the most common adverse reactions (≥20%) reported in patients receiving OPDIVO (n=406) vs everolimus (n=397) were fatigue (56% vs 57%), cough (34% vs 38%), nausea (28% vs 29%), rash (28% vs 36%), dyspnea (27% vs 31%), diarrhea (25% vs 32%), constipation (23% vs 18%), decreased appetite (23% vs 30%), back pain (21% vs 16%), and arthralgia (20% vs 14%). In Checkmate 205 and 039, the most common adverse reactions (≥20%) reported in patients receiving OPDIVO (n=266) were upper respiratory tract infection (44%), fatigue (39%), cough (36%), diarrhea (33%), pyrexia (29%), musculoskeletal pain (26%), rash (24%), nausea (20%) and pruritus (20%). In Checkmate 141, the most common adverse reactions (≥10%) in patients receiving OPDIVO (n=236) were cough (14%) and dyspnea (14%) at a higher incidence than investigator’s choice. In Checkmate 275, the most common adverse reactions (≥20%) reported in patients receiving OPDIVO (n=270) were fatigue (46%), musculoskeletal pain (30%), nausea (22%), and decreased appetite (22%). In Checkmate 142 in MSI-H/dMMR mCRC patients receiving OPDIVO as a single agent (n=74), the most common adverse reactions (≥20%) were fatigue (54%), diarrhea (43%), abdominal pain (34%), nausea (34%), vomiting (28%), musculoskeletal pain (28%), cough (26%), pyrexia (24%), rash (23%), constipation (20%), and upper respiratory tract infection (20%). In Checkmate 142 in MSI-H/dMMR mCRC patients receiving OPDIVO with YERVOY (n=119), the most common adverse reactions (≥20%) were fatigue (49%), diarrhea (45%), pyrexia (36%), musculoskeletal pain (36%), abdominal pain (30%), pruritus (28%), nausea (26%), rash (25%), decreased appetite (20%), and vomiting (20%). In Checkmate 040, the most common adverse reactions (≥20%) in patients receiving OPDIVO with YERVOY (n=49), were rash (53%), pruritus (53%), musculoskeletal pain (41%), diarrhea (39%), cough (37%), decreased appetite (35%), fatigue (27%), pyrexia (27%), abdominal pain (22%), headache (22%), nausea (20%), dizziness (20%), hypothyroidism (20%), and weight decreased (20%). In Checkmate 238, the most common adverse reactions (≥20%) reported in OPDIVO-treated patients (n=452) vs ipilimumab-treated patients (n=453) were fatigue (57% vs 55%), diarrhea (37% vs 55%), rash (35% vs 47%), musculoskeletal pain (32% vs 27%), pruritus (28% vs 37%), headache (23% vs 31%), nausea (23% vs 28%), upper respiratory infection (22% vs 15%), and abdominal pain (21% vs 23%). The most common immune-mediated adverse reactions were rash (16%), diarrhea/colitis (6%), and hepatitis (3%). In Attraction-3, the most common adverse reactions (≥20%) in OPDIVO-treated patients (n=209) were rash (22%) and decreased appetite (21%). In Checkmate 577, the most common adverse reactions (≥20%) in patients receiving OPDIVO (n=532) were fatigue (34%), diarrhea (29%), nausea (23%), rash (21%), musculoskeletal pain (21%), and cough (20%). In Checkmate 649, the most common adverse reactions (≥20%) in patients treated with OPDIVO in combination with chemotherapy (n=782) were peripheral neuropathy (53%), nausea (48%), fatigue (44%), diarrhea (39%), vomiting (31%), decreased appetite (29%), abdominal pain (27%), constipation (25%), and musculoskeletal pain (20%).

Please see US Full Prescribing Information for OPDIVO and YERVOY.

Clinical Trials and Patient Populations

Checkmate 037–previously treated metastatic melanoma; Checkmate 066–previously untreated metastatic melanoma; Checkmate 067–previously untreated metastatic melanoma, as a single agent or in combination with YERVOY; Checkmate 227–previously untreated metastatic non-small cell lung cancer, in combination with YERVOY; Checkmate 9LA–previously untreated recurrent or metastatic non-small cell lung cancer in combination with YERVOY and 2 cycles of platinum-doublet chemotherapy by histology; Checkmate 017–second-line treatment of metastatic squamous non-small cell lung cancer; Checkmate 057–second-line treatment of metastatic non-squamous non-small cell lung cancer; Checkmate 743–previously untreated unresectable malignant pleural mesothelioma, in combination with YERVOY; Checkmate 214–previously untreated renal cell carcinoma, in combination with YERVOY; Checkmate 9ER–previously untreated renal cell carcinoma, in combination with cabozantinib; Checkmate 025–previously treated renal cell carcinoma; Checkmate 205/039–classical Hodgkin lymphoma; Checkmate 141–recurrent or metastatic squamous cell carcinoma of the head and neck; Checkmate 275–urothelial carcinoma; Checkmate 142–MSI-H or dMMR metastatic colorectal cancer, as a single agent or in combination with YERVOY; Checkmate 040–hepatocellular carcinoma, in combination with YERVOY; Checkmate 238–adjuvant treatment of melanoma; Attraction-3–esophageal squamous cell carcinoma; Checkmate 577–adjuvant treatment of esophageal or gastroesophageal junction cancer; Checkmate 649–previously untreated advanced or metastatic gastric or gastroesophageal junction or esophageal adenocarcinoma.

About the Bristol Myers Squibb and Ono Pharmaceutical Collaboration

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

About Bristol Myers Squibb

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

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

Cautionary Statement Regarding Forward-Looking Statements

This press release contains “forward-looking statements” within the meaning of the Private Securities Litigation Reform Act of 1995 regarding, among other things, the research, development and commercialization of pharmaceutical products. All statements that are not statements of historical facts are, or may be deemed to be, forward-looking statements. Such forward-looking statements are based on historical performance and current expectations and projections about our future financial results, goals, plans and objectives and involve inherent risks, assumptions and uncertainties, including internal or external factors that could delay, divert or change any of them in the next several years, that are difficult to predict, may be beyond our control and could cause our future financial results, goals, plans and objectives to differ materially from those expressed in, or implied by, the statements. These risks, assumptions, uncertainties and other factors include, among others, the possibility that the combination treatments not receive regulatory approval for the indications described in this release in the currently anticipated timeline or at all, any marketing approvals, if granted, may have significant limitations on their use, and, if approved, whether such combination treatments for such indications 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, 2020, 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.

corporatefinancial-news

BMY – Bristol Myers Squibb (BMY) Stock Moves -0.19%: What You Should Know

In the latest trading session, Bristol Myers Squibb (BMY Free Report) closed at $67.30, marking a -0.19% move from the previous day. This move was narrower than the S&P 500’s daily loss of 0.75%.

Heading into today, shares of the biopharmaceutical company had gained 0.99% over the past month, outpacing the Medical sector’s loss of 4.84% and lagging the S&P 500’s gain of 2.74% in that time.

BMY will be looking to display strength as it nears its next earnings release, which is expected to be July 28, 2021. In that report, analysts expect BMY to post earnings of $1.90 per share. This would mark year-over-year growth of 16.56%. Meanwhile, the Zacks Consensus Estimate for revenue is projecting net sales of $11.29 billion, up 11.49% from the year-ago period.

For the full year, our Zacks Consensus Estimates are projecting earnings of $7.46 per share and revenue of $45.92 billion, which would represent changes of +15.84% and +7.99%, respectively, from the prior year.

It is also important to note the recent changes to analyst estimates for BMY. These revisions help to show the ever-changing nature of near-term business trends. With this in mind, we can consider positive estimate revisions a sign of optimism about the company’s business outlook.

Research indicates that these estimate revisions are directly correlated with near-term share price momentum. Investors can capitalize on this by using the Zacks Rank. This model considers these estimate changes and provides a simple, actionable rating system.

Ranging from #1 (Strong Buy) to #5 (Strong Sell), the Zacks Rank system has a proven, outside-audited track record of outperformance, with #1 stocks returning an average of +25% annually since 1988. Within the past 30 days, our consensus EPS projection has moved 0.03% lower. BMY is currently sporting a Zacks Rank of #3 (Hold).

In terms of valuation, BMY is currently trading at a Forward P/E ratio of 9.04. This valuation marks a discount compared to its industry’s average Forward P/E of 24.76.

It is also worth noting that BMY currently has a PEG ratio of 1.3. This metric is used similarly to the famous P/E ratio, but the PEG ratio also takes into account the stock’s expected earnings growth rate. BMY’s industry had an average PEG ratio of 1.3 as of yesterday’s close.

The Medical – Biomedical and Genetics industry is part of the Medical sector. This industry currently has a Zacks Industry Rank of 204, which puts it in the bottom 20% of all 250+ industries.

The Zacks Industry Rank gauges the strength of our industry groups by measuring the average Zacks Rank of the individual stocks within the groups. Our research shows that the top 50% rated industries outperform the bottom half by a factor of 2 to 1.

To follow BMY in the coming trading sessions, be sure to utilize Zacks.com.

BMY – Can Gilead Beat Bristol Myers Squibb With Its Cancer CAR-T Therapy?

Bristol Myers Squibb (NYSE:BMY) could have a big winner with Breyanzi, the chimeric antigen T cell (CAR-T) therapy that it gained with the acquisition of Celgene. However, the current king of CAR-T, Gilead Sciences (NASDAQ:GILD), won’t be easily dethroned. In this Motley Fool Live video recorded on June 30, 2021, Motley Fool contributors Keith Speights and Brian Orelli discuss whether or not Gilead will be able to beat BMS in treating large B-cell lymphoma.

Keith Speights: Bristol Myers Squibb impressed investors earlier this month with really positive data for its CAR-T therapy Breyanzi which was formerly liso-cel, which is easier to pronounce to me, I’ll call it liso-cel, and those results were in treating second-line large B-cell lymphomas.

But now Gilead Sciences has announced its own positive results for its CAR-T therapy Yescarta in the very same indication. Brian, do you think Gilead Sciences could beat Bristol Myers Squibb in this indication, or will this be a draw, or could Bristol Myers Squibb come out on top?

Brian Orelli: Unfortunately, we don’t have any data on Bristol Myers Squibb’s Breyanzi.

Speights: We can call it liso-cel if you want to. [laughs]

Orelli: Although even liso-cel is a shortened name for something that we can’t pronounce.

Speights: Exactly. [laughs]

Orelli: Bristol Myers Squibb didn’t release any data from their study. The company only noted that an independent review committee concluded that the treatment improved event-free survival, complete response rate, and progression-free survival compared to the standard of care.

We know it did really well, we just don’t know how well “really well” is. Gilead did present some data for Yescarta. It improved event-free survival by just over 60 percent, it also beat standard of care for objective response rate, although they didn’t give any data for that measurement.

Both the drugs are approved for later stage, after patients have been given two or more treatments. This would move them up one category so that they would be approved after patients had failed one treatment.

The approvals are based on new data, will move them earlier into the paradigm, and that will give them potentially more patients because some patients are cured and others die during the second line, and so by moving from third line to second line, they’ll potentially increase their potential market.

I think it’s definitely too early to declare a winner since we don’t have any Bristol Myers data. If the efficacy is close, it might actually end up coming down to the side effects of the two different drugs.

Manufacturing capacity could be another issue here. Both drugs need to be made individually for each patient, so the question is: Can either of the patients handle all of the second-line patients? Then Yescarta has also proved for another lymphoma, so they would have to tap the capacity for that indication as well as moving from third line to second line in the B-cell indication.

Speights: You pointed out these are really expensive therapies because of all that’s involved with the CAR-T therapies. Don’t you think it’s possible too that we could see off-the-shelf CAR-T therapies coming onto the scene within the next few years that maybe in time could even make these drugs obsolete? And I say in time, nothing immediate here.

Orelli: Yeah. I think it’s going to be a couple of years, and then the biggest issue with the off-the-shelf CAR-Ts is side effect profiles. The CAR-Ts where they’re made from the patient’s own cells have some issues of their own, but the one issue that they don’t have is your immune system isn’t trying to fight off the CAR-Ts from somebody else.

So I think that they have some advantage over the off-the-shelf CAR-Ts. But the off-the-shelf CAR-Ts are obviously going to be a lot cheaper and a lot easier to administer, and they can be administered a lot quicker, and so they have a lot of advantages. But they have to make sure that the efficacy is the same or better, and then that the side effect profile is the same or better.

This article represents the opinion of the writer, who may disagree with the “official” recommendation position of a Motley Fool premium advisory service. We’re motley! Questioning an investing thesis — even one of our own — helps us all think critically about investing and make decisions that help us become smarter, happier, and richer.

BMY – Bristol Myers Squibb (BMY) Stock Moves -0.67%: What You Should Know

Bristol Myers Squibb (BMY Free Report) closed the most recent trading day at $66.69, moving -0.67% from the previous trading session. This change was narrower than the S&P 500’s 0.86% loss on the day.

Heading into today, shares of the biopharmaceutical company had gained 2.66% over the past month, outpacing the Medical sector’s gain of 1.36% and lagging the S&P 500’s gain of 3.22% in that time.

Wall Street will be looking for positivity from BMY as it approaches its next earnings report date. This is expected to be July 28, 2021. In that report, analysts expect BMY to post earnings of $1.92 per share. This would mark year-over-year growth of 17.79%. Our most recent consensus estimate is calling for quarterly revenue of $11.33 billion, up 11.84% from the year-ago period.

Looking at the full year, our Zacks Consensus Estimates suggest analysts are expecting earnings of $7.46 per share and revenue of $46 billion. These totals would mark changes of +15.84% and +8.18%, respectively, from last year.

Any recent changes to analyst estimates for BMY should also be noted by investors. Recent revisions tend to reflect the latest near-term business trends. As such, positive estimate revisions reflect analyst optimism about the company’s business and profitability.

Based on our research, we believe these estimate revisions are directly related to near-team stock moves. Investors can capitalize on this by using the Zacks Rank. This model considers these estimate changes and provides a simple, actionable rating system.

The Zacks Rank system ranges from #1 (Strong Buy) to #5 (Strong Sell). It has a remarkable, outside-audited track record of success, with #1 stocks delivering an average annual return of +25% since 1988. Over the past month, the Zacks Consensus EPS estimate has moved 0.17% higher. BMY currently has a Zacks Rank of #3 (Hold).

In terms of valuation, BMY is currently trading at a Forward P/E ratio of 9. This valuation marks a discount compared to its industry’s average Forward P/E of 23.53.

Also, we should mention that BMY has a PEG ratio of 1.29. This popular metric is similar to the widely-known P/E ratio, with the difference being that the PEG ratio also takes into account the company’s expected earnings growth rate. BMY’s industry had an average PEG ratio of 1.38 as of yesterday’s close.

The Medical – Biomedical and Genetics industry is part of the Medical sector. This industry currently has a Zacks Industry Rank of 213, which puts it in the bottom 17% of all 250+ industries.

The Zacks Industry Rank includes is listed in order from best to worst in terms of the average Zacks Rank of the individual companies within each of these sectors. Our research shows that the top 50% rated industries outperform the bottom half by a factor of 2 to 1.

Make sure to utilize Zacks. Com to follow all of these stock-moving metrics, and more, in the coming trading sessions.

BMY – Bristol Myers Squibb (BMY) Dips More Than Broader Markets: What You Should Know

Bristol Myers Squibb (BMY Free Report) closed the most recent trading day at $65.26, moving -1.03% from the previous trading session. This move lagged the S&P 500’s daily loss of 0.11%.

Heading into today, shares of the biopharmaceutical company had lost 1.23% over the past month, lagging the Medical sector’s gain of 2.36% and the S&P 500’s gain of 2.23% in that time.

Investors will be hoping for strength from BMY as it approaches its next earnings release, which is expected to be July 28, 2021. In that report, analysts expect BMY to post earnings of $1.92 per share. This would mark year-over-year growth of 17.79%. Meanwhile, the Zacks Consensus Estimate for revenue is projecting net sales of $11.33 billion, up 11.84% from the year-ago period.

BMY’s full-year Zacks Consensus Estimates are calling for earnings of $7.46 per share and revenue of $46 billion. These results would represent year-over-year changes of +15.84% and +8.18%, respectively.

Any recent changes to analyst estimates for BMY should also be noted by investors. These recent revisions tend to reflect the evolving nature of short-term business trends. As such, positive estimate revisions reflect analyst optimism about the company’s business and profitability.

Our research shows that these estimate changes are directly correlated with near-term stock prices. To benefit from this, we have developed the Zacks Rank, a proprietary model which takes these estimate changes into account and provides an actionable rating system.

The Zacks Rank system, which ranges from #1 (Strong Buy) to #5 (Strong Sell), has an impressive outside-audited track record of outperformance, with #1 stocks generating an average annual return of +25% since 1988. Over the past month, the Zacks Consensus EPS estimate has moved 0.17% higher. BMY is currently a Zacks Rank #3 (Hold).

Looking at its valuation, BMY is holding a Forward P/E ratio of 8.84. For comparison, its industry has an average Forward P/E of 21.8, which means BMY is trading at a discount to the group.

Meanwhile, BMY’s PEG ratio is currently 1.27. This metric is used similarly to the famous P/E ratio, but the PEG ratio also takes into account the stock’s expected earnings growth rate. The Medical – Biomedical and Genetics industry currently had an average PEG ratio of 1.41 as of yesterday’s close.

The Medical – Biomedical and Genetics industry is part of the Medical sector. This industry currently has a Zacks Industry Rank of 209, which puts it in the bottom 18% of all 250+ industries.

The Zacks Industry Rank gauges the strength of our industry groups by measuring the average Zacks Rank of the individual stocks within the groups. Our research shows that the top 50% rated industries outperform the bottom half by a factor of 2 to 1.

To follow BMY in the coming trading sessions, be sure to utilize Zacks.com.

BMY – Eisai and Bristol Myers Squibb Enter Into Global Strategic Collaboration for Eisai's MORAb-202 Antibody Drug Conjugate

TOKYO & NEW YORK–()–Eisai Co., Ltd. and Bristol-Myers Squibb Company (NYSE: BMY) announced today that the companies have entered into an exclusive global strategic collaboration agreement for the co-development and co-commercialization of MORAb-202, an antibody drug conjugate (ADC). MORAb-202 is Eisai’s first ADC and combines Eisai’s in house developed anti-folate receptor alpha (FRα) antibody, and Eisai’s anticancer agent eribulin, using an enzyme cleavable linker. It is a potential best-in-class FRα ADC with a favorable pharmacology profile and demonstrated single agent activity in patients with advanced solid tumors. Eisai is currently investigating MORAb-202 in FRα-positive solid tumors (inclusive of endometrial, ovarian, lung and breast cancers) in two studies: a Phase 1 clinical study in Japan and a Phase 1/2 clinical study in the United States. The companies are planning to move into the registrational stage of development for this asset as early as next year.

Under the agreement, Eisai and Bristol Myers Squibb will jointly develop and commercialize MORAb-202 in the following collaboration territories: Japan; China; countries in the Asia-Pacific region*; the United States; Canada; Europe, including the European Union and the United Kingdom; and Russia. Bristol Myers Squibb will be solely responsible for developing and commercializing the drug in regions outside of the collaboration territories. Eisai will remain responsible for the manufacturing and supply of MORAb-202 globally.

Under the financial terms of the agreement, Bristol Myers Squibb will pay $650 million U.S. dollars to Eisai including $200 million U.S. dollars as payment toward Eisai research and development expenses. Eisai is also entitled to receive up to $2.45 billion U.S. dollars in potential future development, regulatory, and commercial milestones. The parties will share profits, research and development and commercialization costs in the collaboration territories and Bristol Myers Squibb will pay Eisai a royalty on sales outside of the collaboration territories. Eisai is expected to book sales of MORAb-202 in Japan, China, countries in the Asia-Pacific region, Europe and Russia. Bristol Myers Squibb is expected to book sales of MORAb-202 in the United States and Canada.

MORAb-202 combines Eisai’s in-house discovered antibody and payload using the company’s advanced chemistry capabilities.” said Haruo Naito, Chief Executive Officer at Eisai. “It is characterized by its payload of eribulin, which is a product of our modern synthetic organic chemistry that has already made contributions to patients with breast cancer and soft tissue sarcoma. Our collaboration with Bristol Myers Squibb will accelerate the development of MORAb-202 with the goal of bringing a potentially impactful treatment option to patients globally.”

This global collaboration with Eisai is an important strategic fit for Bristol Myers Squibb as it extends our leading position in oncology with a differentiated asset that complements our broad solid tumor portfolio and leverages our deep internal development expertise.” said Giovanni Caforio, M.D., board chair and chief executive officer, Bristol Myers Squibb. “We look forward to collaborating with Eisai as we work to bring this potential treatment option to patients in need as soon as possible.”

* South Korea, Taiwan, Hong Kong, Macau, Philippines, Vietnam, Lao People’s Democratic Republic, Thailand, Cambodia, Malaysia, Singapore, Indonesia, India, Australia, New Zealand

About Eisai Co., Ltd.

Eisai is a leading global research and development-based pharmaceutical company headquartered in Japan, with approximately 10,000 employees worldwide. Eisai defines our corporate mission as “giving first thought to patients and their families and to increasing the benefits health care provides,” which we call our human health care (hhc) philosophy. We strive to realize our hhc philosophy by delivering innovative products in therapeutic areas with high unmet medical needs, including Oncology and Neurology. In the spirit of hhc, Eisai takes that commitment even further by applying our scientific expertise, clinical capabilities and patient insights to discover and develop innovative solutions that help address society’s toughest unmet needs, including neglected tropical diseases and the Sustainable Development Goals.

For more information about Eisai, please visit www.eisai.com (for global), us.eisai.com (for U.S.) or www.eisai.eu (for Europe, Middle East, Africa), and connect with us on Twitter (U.S. and global) and LinkedIn (for U.S.).

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 and Facebook.

About MORAb-202

MORAb-202 is Eisai’s first antibody drug conjugate (ADC) that is composed of Eisai’s in-house developed anticancer agent farletuzumab, a humanized IgG1 monoclonal antibody that binds to the folate receptor alpha (FRα), and Eisai’s in-house developed anticancer agent eribulin, using an enzyme cleavable linker. Eisai is currently conducting a Phase 1 clinical study in Japan and a Phase 1/2 clinical study in the United States, respectively, for MORAb-202 targeting FRα-positive solid tumors. After MORAb-202 enters the target FRα-positive cancer cells, the linker is enzymatically cleaved, releasing eribulin from the antibody leading to its antitumor activity. Furthermore, in non-clinical studies, MORAb-202 demonstrated a bystander effect, with antitumor activity on the FRα-negative cancer cells surrounding the FRα-positive cancer cells.

The payload eribulin (product name: Halaven) is the first in the halichondrin class of microtubule dynamics inhibitors with a novel mechanism of action. Structurally eribulin is a simplified and synthetically produced version of halichondrin B, a natural product isolated from the marine sponge Halichondria okadai, and functions by inhibiting the growth phase of microtubule dynamics which prevents cell division. Eribulin is currently approved for use in the treatment of breast cancer in over 75 countries worldwide, including Japan, the United States, Europe, China, and other countries in Asia. Furthermore, eribulin is approved for use in the treatment of liposarcoma (soft tissue sarcoma in Japan) in over 75 countries worldwide, including Japan, the United States, as well as countries in Europe and Asia.

Bristol Myers Squibb Forward-Looking Statement

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 and the collaboration. 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 the expected benefits of, and opportunities related to, the collaboration may not be realized by Bristol Myers Squibb or may take longer to realize than anticipated, that MORAb‑202 may not achieve its primary study endpoints or receive regulatory approval for the indications described in this release in the currently anticipated timeline or at all and, if approved, whether such product candidate for such indications 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, 2020, 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.

CorporateFinancial-news

BMY – Bristol Myers Squibb Stock Remains Undervalued After Positive Data From Clinical Trials

[Updated: 6/14/2021] BMS Positive Data From Clinical Trials

The stock price of Bristol Myers Squibb (NYSE: BMY) has seen a 3% rise in yesterday’s trading session (Jun 10), after the company announced positive data from phase three clinical trials of Breyanzi as a second line treatment in adults with relapsed or refractory large B-cell lymphoma. Breyanzi is Bristol Myers Squibb’s chimeric antigen receptor T cell (CAR-T) therapy, which was first approved by the U.S. FDA in Feb 2021 for the treatment of LBCL after two or more lines of systemic therapy. The recent development means Bristol Myers Squibb is all set to challenge Novartis and Gilead Lifesciences, that currently offer therapies for the treatment of LBCL.

In another development, the company announced positive data from phase two clinical trials of Reblozyl, for treatment of adults with non-transfusion dependent beta Thalassemia. Note that Reblozyl is already approved by the U.S. FDA for the treatment of Anemia in adults with beta Thalassemia who require regular red blood cell transfusions, and to treat Anemia in adults with lower-risk Myelodysplastic Syndromes.

While Breyanzi’s peak sales are estimated to be around $1.0 billion, that for Reblozyl are touted to be north of $2.0 billion. Label expansion for these drugs will likely result in higher sales going forward. Earlier in March 2021, Bristol Myers Squibb also secured approval for another CAR-T therapy – Abecma – for the treatment of relapsed multiple myeloma after four or more prior lines of therapy.

These developments will bode well for BMY stock going forward. BMY stock has risen by only 19% over the last one year, underperforming the broader markets, with the S&P 500 up 32%. This can partly be attributed to lower than estimated Q1 results, and weak sales for the company’s blockbuster drug – Opdivo. However, we continue to believe that BMY stock is undervalued. Going by our Bristol Myers Squibb Valuation of $80, based on expected adjusted EPS of $7.55 and a P/E multiple of 11x for 2021, there is over 18% upside potential from the current levels of around $67.

[Updated: 4/30/2021] BMY Stock Falls Post Q1

The stock price of Bristol Myers Squibb has seen a 5% drop over the last five trading days, after the company announced its Q1 results, which were slightly below the street estimates. Bristol’s Q1 revenue of $11.1 billion was largely in-line with the consensus estimates, while its adjusted EPS of $1.74 per share was short of the $1.82 consensus estimate. The results were impacted by Covid-19 to some extent and we believe that the company will likely see strong sales growth over the coming quarters, led by market share gains for Eliquis, and recent approvals boding well for Opdivo and Yervoy.

That said, the investors weren’t happy with Bristol’s Q1 performance and the stock plunged 5% in a single trading session, post the earnings announcement. Now that half of the U.S. population has received at least one dose of vaccine, the economy is expected to open up gradually, signaling improvement for Bristol stock over the coming quarters.

Going by historical performance, there is a 62% chance of a rise in BMY stock over the next month. Out of 116 instances in the last ten years that BMY stock saw a five-day decline of 5.2% or more, 72 of them resulted in BMY stock rising over the subsequent one month period (twenty-one trading days). This historical pattern reflects 72 out of 116, or about a 62% chance of gain in BMY stock over the coming month. Furthermore, Bristol has kept its adjusted earnings guidance unchanged for the full year, and we also maintain Bristol Myers Squibb’s Valuation of $80, based on an EPS estimate of $7.55 and a P/E multiple of 11x in 2021, reflecting a 26% premium to the current market price of around $63.

At the current market price of $63, BMY stock is now trading at just 8x its 2021 EPS estimate of $7.55. The 8x figure compares with levels of over 13x seen in 2018 and 2019, and a 10x figure seen as recently as late 2020. We continue to believe that BMY stock is undervalued and it can offer high returns going forward.

[Updated: 3/29/2021] BMY CAR-T Approval

The U.S. FDA has approved Abecma, a CAR-T (chimeric antigen receptor T cells) cell immunotherapy for the treatment of relapsed multiple myeloma after four or more prior lines of therapy. Abecma was being developed by Bristol Myers Squibb and bluebird bio Inc. CAR-T therapy refers to extraction of a patient’s own T cells, which are then genetically modified and infused back into the patient’s body. These T-Cells target and destroy any abnormal cells, including cancer cells. This is an important win for Bristol Myers Squibb and bluebird bio, given that the CAR-T therapy is expected to grow at a massive 45% CAGR over the next ten years. Many large pharmaceutical companies, including Bristol Myers Squibb, are working on CAR-T therapies. That said, the recent approval marks the only approved CAR-T therapy for the treatment of multiple myeloma. The stock prices of both Bristol Myers Squibb and bluebird bio are expected to see an uptick post this announcement.

Last week, we also discussed how BMY’s stock looks undervalued at $63, given that multiple positive triggers are expected in the near term, including the FDA approvals. After the multiple myeloma CAR-T therapy approval, eyes will now be on the FDA’s decision regarding Opdivo’s use for additional indications, as well as Zeposia in ulcerative colitis. We continue to believe that BMY stock is undervalued currently, given the low P/E multiple of under 10x it currently trades at, compared to levels north of 13x seen over the recent years. Our dashboard, ‘What Factors Drove 21% Change In Bristol Myers Squibb Stock between 2018 and now?‘, has the underlying numbers.

[Updated: 3/26/2021] BMY Stock Looks Undervalued At $63

Bristol Myers Squibb (NYSE: BMY) looks very attractive at current levels of $63, as it is up only 40% from the levels it was at on March 23, 2020, when broader markets made a bottom due to the spread of Covid-19. This marks an underperformance compared to the S&P which has moved 75% since its March 2020 lows, with the resumption of economic activities as lockdowns are gradually lifted and vaccination programs have been initiated in multiple countries. This underperformance can primarily be attributed to investors concerns over the long term growth of the company. The company’s largest drug – Revlimid – which garnered $12 billion in 2020 sales, will lose its market exclusivity next year, implying a decline in sales, as generics gain market share. However, we believe that the stock is undervalued at the current levels of $63. Our dashboard, ‘What Factors Drove 21% Change In Bristol Myers Squibb Stock between 2018 and now?‘, has the underlying numbers.

Now, the company has given a guidance of low to mid-single-digit top-line expansion through 2025, which we believe to be conservative. Note that Bristol Myers Squibb has already entered into agreements with multiple companies, including Dr. Reddy’s Laboratories, Natco Pharma, and Alvogen to launch their generic version of Revlimid in limited volume post March 2022. The agreement with Dr. Reddy’s, for instance, will allow the Indian pharmaceutical company to sell its generic version without any volume limit only after January 2026. This essentially implies that Revlimid sales will not see a sharp drop in the first year of patent expiry. In fact, we estimate $10 billion in sales from Revlimid in 2025, post which, it will likely see a sharp decline. As we look forward, there are multiple positive triggers expected for the company. The FDA is expected to review Bristol Myers Squibb’s Opdivo for additional indications and Zeposia for treating ulcerative colitis. Note that Zeposia’s peak sales could be north of $5 billion, if it manages to secure regulatory approvals for ulcerative colitis and inflammatory bowel disease. In March 2020, Zeposia secured its first regulatory approval for relapsing forms of Multiple Sclerosis.

Not to forget, Eliquis, Bristol Myers Squibb’s oral blood thinner, which has added over $1 billion in incremental sales each year since 2014, a trend which now appears will continue for a few more years. In August 2020, a U.S. district court upheld the patents for Eliquis, with composition of matter patent expiring in 2026 and a formulation patent stretching out to 2031. This implies that Eliquis’ peak sales can be north of $13 billion in 2025, compared to $9 billion in 2020.

Overall, we believe that the company should do better than its guidance of low to mid-single-digit growth through 2025. The company is also sitting on cash of around $16 billion, and it won’t be surprising if it decided to consider more acquisitions to further boost its pipeline.

Lastly, let us look at the current valuation. At the current price of $63, BMY stock is trading at 8x its estimated 2021 adjusted earnings of $7.50 per share. This compares with levels of 15x seen in 2017, and over 10x seen in 2018 and 2019. If we look at some of the other pharmaceutical companies, J&J trades at 17x, Merck at 12x, Pfizer at 11x, and Eli Lilly at 22x forward annual earnings. This strengthens our view that BMY stock is undervalued at current levels, compared to both its own historical levels, as well as compared to its peers.

[Updated: 11/30/2020] BMY Stock Performance

We believe that Bristol Myers Squibb stock (NYSE: BMY) is a good buying opportunity at the present time. BMY stock trades near $63 currently and it is, in fact, down 6% from its pre-Covid high of $67 in February 2020 – just before the coronavirus pandemic hit the world. BMY stock has rallied over 35% since its March lows of $46, compared to a 63% gains for S&P 500. The underperformance can partly be attributed to the weaker than estimated sales of its blockbuster drug – Opdivo. That said, the company’s overall Q3 performance was better than street estimates, and now with economies opening up, the company will likely see improved sales growth and margin expansion, driving the stock higher from here, in our view. Our conclusion is based on our comparative analysis of Bristol Myers Squibb stock performance during the current financial crisis with that during the 2008 recession in our interactive dashboard.

2020 Coronavirus Crisis

Timeline of 2020 Crisis So Far:

  • 12/12/2019: Coronavirus cases first reported in China
  • 1/31/2020: WHO declares a global health emergency.
  • 2/19/2020: Signs of effective containment in China and hopes of monetary easing by major central banks helps S&P 500 reach a record high
  • 3/23/2020: S&P 500 drops 34% from the peak level seen on Feb 19, as COVID-19 cases accelerate outside China. Doesn’t help that oil prices crash in mid-March amid Saudi-led price war
  • Since 3/24/2020: S&P 500 recovers 62% from the lows seen on Mar 23, as the Fed’s multi-billion dollar stimulus package suppresses near-term survival anxiety and infuses liquidity into the system.

In contrast, here is how BMY stock and the broader market fared during the 2007-08 crisis

Timeline of 2007-08 Crisis

  • 10/1/2007: Approximate pre-crisis peak in S&P 500 index
  • 9/1/2008 – 10/1/2008: Accelerated market decline corresponding to Lehman bankruptcy filing (9/15/08)
  • 3/1/2009: Approximate bottoming out of S&P 500 index
  • 12/31/2009: Initial recovery to levels before accelerated decline (around 9/1/2008)

BMY and S&P 500 Performance Over 2007-08 Financial Crisis

BMY stock declined from levels of about $29 in September 2007 (pre-crisis peak) to levels of $18 in March 2009 (as the markets bottomed out), implying BMY stock lost 37%. It recovered post the 2008 crisis, rallying 37% to levels of $25 by January 2010. In comparison, the S&P 500 Index saw a decline of 51% from its peak in September 2007 to its bottom in March 2009, followed by a sharp recovery of 48% by January 2010.

Bristol Myers Squibb Company Fundamentals Over Recent Years Have Been Strong

Bristol Myers Squibb’s revenues increased from $19.4 billion in 2016 to $26.1 billion in 2019, due to market share gains for its anticoagulant – Eliquis, along with the partial contribution of Celgene, which was acquired in 2019. The company has also seen its Net Margins expand from 24.5% to 30.7% on an adjusted basis, aiding its EPS, which grew from $2.83 to $4.69 over the same period. More recently, Bristol Myers Squibb garnered over $10.5 billion in sales, reflecting 75% growth y-o-y in Q3 2020. The growth primarily reflects the impact of the Celgene merger, along with continued uptick in Eliquis, which grew 9% to $2.1 billion, while Opdivo saw a decline of 2% with sales of $1.8 billion during the quarter. The slowdown in Opdivo’s sales growth was anticipated, amid Merck’s Keytruda gaining market share. Looking at the bottom line, the company reported adjusted EPS of $1.63, reflecting 39% y-o-y growth.

Does Bristol Myers Squibb Have Sufficient Cash Cushion To Meet Its Obligations Through The Coronavirus Crisis?

Bristol Myers Squibb’s total debt increased from $7 billion in 2016 to $45 billion at the end of Q3 2020 (primarily due to the Celgene acquisition), while its total cash increased from $9 billion to $22 billion over the same period. Bristol Myers Squibb generated $10 billion cash from operations in the first nine months of 2020. While the company’s debt levels are high, the company has enough liquidity cushion to weather the current crisis.

Conclusion

Phases of Covid-19 Crisis:

  • Early- to mid-March 2020: Fear of the coronavirus outbreak spreading rapidly translates into reality, with the number of cases accelerating globally
  • Late-March 2020 onward: Social distancing measures + lockdowns
  • April 2020: Fed stimulus suppresses near-term survival anxiety
  • May-June 2020: Recovery of demand, with gradual lifting of lockdowns – no panic anymore despite a steady increase in the number of cases
  • July-October 2020: After poor Q2 results, Q3 expectations were lukewarm, but continued improvement in demand, and progress with vaccine development buoyed market sentiment

As the global economy opens up and lockdowns are lifted in phases, consumer demand is expected to pick up. This could be reflected in the form of a pick-up in revenue toward the end of 2020, followed by revenue growth in 2021, boding well for the BMY stock in the near term. While BMY stock has 6% upside for it to recover to pre-Covid highs, we believe the stock could trend much higher than that in the near term.

What if you’re looking for a more balanced portfolio instead? Here’s a high-quality portfolio to beat the market, with over 100% return since 2016, versus 55% for the S&P 500. Comprised of companies with strong revenue growth, healthy profits, lots of cash, and low risk, it has outperformed the broader market year after year, consistently.

See all Trefis Featured Analyses and Download Trefis Data here

BMY – How Big Is Bristol Myers Squibb's Latest FDA Approval?

Bristol Myers Squibb (NYSE:BMY) recently picked up another U.S. Food and Drug Administration (FDA) approval for Zeposia in treating ulcerative colitis. In this Motley Fool Live video recorded on June 2, Motley Fool contributors Keith Speights and Brian Orelli discuss just how big this FDA win is for Bristol Myers Squibb.

Keith Speights: The FDA recently approved Bristol Myers Squibb’s Zeposia. It’s also known as ozanimod. This approval was for treating ulcerative colitis. This is Bristol Myers Squibb’s first win in a gastrointestinal indication. Brian, how big is this for the company?

Brian Orelli: Yes. This is Celgene’s old multiple sclerosis drug and it had some issues with the FDA. The FDA gave it a Refuse to File, you recall, because they had some issues with the breakdown products. They hadn’t characterized the products that gets broken down once it goes into the humans. It did eventually get approved for multiple sclerosis in March of 2020.

Now in ulcerative colitis, I think it’s going to have a lot of competition. There are quite a few drugs that are approved for that indication. There’s three different TNF inhibitors; Remicade and Simponi from Johnson & Johnson, and Humira from AbbVie, and then Takeda and Johnson & Johnson also have other biologics that are approved for ulcerative colitis.

That’s just the biologics. This is progressive disease, and patients would start on generic anti-inflammatory drug, and then move up maybe to small molecule branded drugs, something like Xeljanz from Pfizer.

I think between the competition and then also the class of drugs that Bristol Myers’ drug is in has had some hard side effects. I think that’s going to cause the drug probably to be a last-line treatment. I think that that could cause some serious problems in terms of getting any reasonable amount of sales from this drug.

Some doctors will use it, and it definitely worked in the clinical trials, although they only tested it against placebo. I think if they had tested it head-to-head against some other drug in the class and it had beat that drug, then you could see doctors rushing to it more. But right now, I think it’ll probably be a wait-and-see and only use it in patients who aren’t responding to a lot of the other drugs.

Speights: Back in the day before Celgene was acquired by Bristol Myers Squibb, Celgene was predicting that Zeposia, or at the time, ozanimod, could reach peak sales of $4 to $6 billion dollars. I don’t think that rosy of an outlook is applicable, and now, for some of the reasons you just mentioned, Brian, you still think this drug might be a blockbuster for Bristol Myers Squibb?

Orelli: I think that probably between multiple sclerosis and ulcerative colitis, I think it probably could be a blockbuster, but certainly not coming out of the gate. It will probably be toward the end of its patent life, it could hit blockbuster status probably.

This article represents the opinion of the writer, who may disagree with the “official” recommendation position of a Motley Fool premium advisory service. We’re motley! Questioning an investing thesis — even one of our own — helps us all think critically about investing and make decisions that help us become smarter, happier, and richer.