U.S. Food and Drug Administration Accepts for Priority Review supplemental Biologics License Application for Reblozyl® (luspatercept-aamt) in Adults with Non-Transfusion Dependent (NTD) Beta Thalassemia

Rhea-AI Summary

Bristol Myers Squibb (NYSE: BMY) announced that the FDA has accepted for priority review the supplemental Biologics License Application for Reblozyl (luspatercept-aamt) to treat anemia in adults with non-transfusion dependent beta thalassemia, with a PDUFA goal date of March 27, 2022. The application is based on Phase 2 BEYOND study results. Additionally, the European Medicines Agency has validated the Type II variation for Reblozyl in this indication. The BEYOND study involved 145 patients, aimed at assessing efficacy and safety.

Positive

• FDA priority review acceptance for Reblozyl could expedite market entry.
• Reblozyl's application is based on reliable Phase 2 BEYOND study results.
• Potential expansion of Reblozyl's indication could increase revenue opportunities.

Negative

• Approval timeline uncertainty could affect market expectations.
• Clinical trial results may face scrutiny during FDA review.
• Dependence on a partnership with Merck for co-development and commercialization.

Submission based on results from Phase 2 BEYOND study of Reblozyl plus best supportive care in adults with NTD beta thalassemia

PRINCETON, N.J.--(BUSINESS WIRE)-- Bristol Myers Squibb (NYSE: BMY) today announced that the U.S. Food and Drug Administration (FDA) has accepted for priority review the supplemental Biologics License Application (sBLA) for Reblozyl^® (luspatercept-aamt), a first-in-class erythroid maturation agent, for the treatment of anemia in adults with non-transfusion dependent (NTD) beta thalassemia. The FDA has set a Prescription Drug User Fee Act (PDUFA) goal date of March 27, 2022. In addition, the European Medicines Agency has validated the Type II variation for Reblozyl in NTD beta thalassemia. Reblozyl is being co-developed and co-commercialized with Merck & Co., Inc., known as MSD outside the United States and Canada, following Merck’s recent acquisition of Acceleron Pharma, Inc.

These applications were based on safety and efficacy results from the pivotal Phase 2 BEYOND study evaluating Reblozyl plus best supportive care in patients with NTD beta thalassemia.

“Patients with non-transfusion dependent beta thalassemia may not require lifelong blood transfusions for survival, but their need for effective treatment options is significant as they face a range of clinical complications due to chronic anemia and iron overload,” said Noah Berkowitz, M.D., Ph.D., senior vice president, Hematology Development, Bristol Myers Squibb. “Reblozyl is an important therapy approved for anemia associated with beta thalassemia and lower-risk myelodysplastic syndromes in multiple countries, including the United States and within the European Union. Along with our partners at Merck, we are committed to continuing to advance our clinical program for Reblozyl and look forward to working with the FDA during its review of our application for this underserved patient population.”

Updated analyses from the BEYOND study will be presented at the 63^rd American Society of Hematology Annual Meeting and Exposition from December 11-14.

About BEYOND

BEYOND (NCT03342404) is a Phase 2, double-blind, randomized, placebo-controlled, multicenter study to determine the efficacy and safety of luspatercept-aamt (ACE-536) versus placebo in adults with non-transfusion dependent beta thalassemia. The study is divided into the Screening Period, Double-blind Treatment Period (DBTP) and Post-Treatment Follow-up Period (PTFP) and randomized 145 subjects at a 2:1 ratio of Reblozyl versus placebo. The primary endpoint of the study is the proportion of subjects who have an increase from baseline ≥1.0 g/dL in mean of hemoglobin values over a continuous 12-week interval from Week 13 to Week 24 of treatment in the absence of transfusions. Key secondary endpoints include mean change in non-transfusion dependent beta thalassemia-patient reported outcome (NTDT-PRO) Tiredness and Weakness (TW) domain score and baseline hemoglobin (Hb).

About Beta Thalassemia

Beta thalassemia is an inherited blood disorder caused by a genetic defect in hemoglobin. It is one of the most common autosomal recessive disorders, and the total annual incidence of symptomatic individuals is estimated at 1 in 100,000 people globally.¹ The disease is associated with ineffective erythropoiesis, which results in the production of fewer and less healthy red blood cells (RBCs), often leading to severe anemia—a condition that can be debilitating and can lead to other complications for patients—as well as other serious health issues. Treatment options for anemia associated with beta thalassemia are limited, consisting mainly of frequent RBC transfusions that have the potential to contribute to iron overload, which can cause serious complications such as organ damage.¹ Non-transfusion dependent thalassemia is a term used to describe patients who do not require lifelong regular transfusions for survival, although they may experience a range of clinical complications and require occasional or even frequent transfusions, usually for defined periods of time.²

About Reblozyl^®

Reblozyl, the first and only erythroid maturation agent, promotes late-stage red blood cell maturation in animal models.¹ Bristol Myers Squibb and Merck & Co., Inc., through Merck’s acquisition of Acceleron, are jointly developing Reblozyl as part of a global collaboration. Reblozyl is currently approved in the U.S. for the treatment of:

• anemia in adult patients with beta thalassemia who require regular red blood cell transfusions, and

• anemia failing an erythropoiesis stimulating agent and requiring 2 or more red blood cell units over 8 weeks in adult patients with very low- to intermediate-risk myelodysplastic syndrome with ring sideroblasts (MDS-RS) or with myelodysplastic/myeloproliferative neoplasm with ring sideroblasts and thrombocytosis (MDS/MPN-RS-T).

Reblozyl is not indicated for use as a substitute for red blood cell transfusions in patients who require immediate correction of anemia.

Important Safety Information

WARNINGS AND PRECAUTIONS

Thrombosis/Thromboembolism

Thromboembolic events (TEE) were reported in 8/223 (3.6%) REBLOZYL-treated patients. TEEs included deep vein thrombosis, pulmonary embolus, portal vein thrombosis and ischemic stroke. Patients with known risk factors for thromboembolism, (splenectomy or concomitant use of hormone replacement therapy), may be at further increased risk of thromboembolic conditions. Consider thromboprophylaxis in patients at increased risk of TEE. Monitor patients for signs and symptoms of thromboembolic events and institute treatment promptly.

Hypertension

Hypertension was reported in 10.7% (61/571) of REBLOZYL-treated patients. Across clinical studies, the incidence of grade 3-4 hypertension ranged from 1.8% to 8.6%. In patients with beta thalassemia with normal baseline blood pressure, 13 (6.2%) patients developed systolic blood pressure (SBP) >130 mm Hg and 33 (16.6%) patients developed diastolic blood pressure (DBP) >80 mm Hg. Monitor blood pressure prior to each administration. Manage new or exacerbations of preexisting hypertension using anti-hypertensive agents.

Embryo-Fetal Toxicity

REBLOZYL may cause fetal harm when administered to a pregnant woman. REBLOZYL caused increased post-implantation loss, decreased litter size, and an increased incidence of skeletal variations in pregnant rat and rabbit studies. Advise pregnant women of the potential risk to a fetus. Advise females of reproductive potential to use effective contraception during treatment and for at least 3 months after the last dose.

ADVERSE REACTIONS

Serious adverse reactions occurring in 1% of patients included cerebrovascular accident and deep vein thrombosis. A fatal adverse reaction occurred in one patient treated with REBLOZYL who died due to an unconfirmed case of AML.

Most common adverse reactions (at least 10% for REBLOZYL, and 1% more than placebo) were headache (26% vs 24%), bone pain (20% vs 8%), arthralgia (19% vs 12%), fatigue (14% vs 13%), cough (14% vs 11%), abdominal pain (14% vs 12%), diarrhea (12% vs 10%) and dizziness (11% vs 5%).¹

LACTATION

It is not known whether REBLOZYL is excreted into human milk or absorbed systemically after ingestion by a nursing infant. REBLOZYL was detected in milk of lactating rats. When a drug is present in animal milk, it is likely that the drug will be present in human milk. Because many drugs are excreted in human milk, and because of the unknown effects of REBLOZYL in infants, a decision should be made whether to discontinue nursing or to discontinue treatment. Because of the potential for serious adverse reactions in the breastfed child, breastfeeding is not recommended during treatment and for 3 months after the last dose.

Please see full Prescribing Information for REBLOZYL

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

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

About Bristol Myers Squibb

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

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

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 Reblozyl (luspatercept-aamt) may not receive regulatory approval for the additional indication described in this release in the currently anticipated timeline or at all, that any marketing approvals, if granted, may have significant limitations on their use, and, if approved, whether such product candidate for such additional indication described in this release will be commercially successful. No forward-looking statement can be guaranteed. Forward-looking statements in this press release should be evaluated together with the many risks and uncertainties that affect Bristol Myers Squibb’s business and market, particularly those identified in the cautionary statement and risk factors discussion in Bristol Myers Squibb’s Annual Report on Form 10-K for the year ended December 31, 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.

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References:

1. Galanello R, Origa R. Beta thalassemia. Orphanet Journal of Rare Diseases. 2010;5(11). Available at: https://ojrd.biomedcentral.com/articles/10.1186/1750-1172-5-11. Accessed November 2021.
2. Musallam, K. M., Rivella, S., Vichinsky, E., & Rachmilewitz, E. A. (2013). Non-transfusion-dependent thalassemias. Haematologica, 98(6), 833–844. https://doi.org/10.3324/haematol.2012.066845. Accessed November 2021.

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Source: Bristol Myers Squibb

FAQ

What is the FDA's decision date for Bristol Myers Squibb's Reblozyl?

The FDA has set a Prescription Drug User Fee Act (PDUFA) goal date of March 27, 2022 for Reblozyl.

What condition is Reblozyl being reviewed for by the FDA?

Reblozyl is under review for the treatment of anemia in adults with non-transfusion dependent beta thalassemia.

What was the basis for the FDA application for Reblozyl?

The application was based on results from the Phase 2 BEYOND study.

What is the significance of the European Medicines Agency's action regarding Reblozyl?

The European Medicines Agency has validated the Type II variation for Reblozyl in non-transfusion dependent beta thalassemia.

How many patients were involved in the BEYOND study for Reblozyl?

The BEYOND study randomized 145 subjects in a 2:1 ratio of Reblozyl versus placebo.