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New England Journal of Medicine Publishes Results from Pivotal Phase 3 BELIEVE Trial of Reblozyl (luspatercept-aamt) in Adult Patients With Beta Thalassemia

March 26, 2020 Off By BusinessWire

Results demonstrate that treatment with Reblozyl provides significant reduction in transfusion burden for patients with beta thalassemia-associated anemia compared to placebo

PRINCETON, N.J. & CAMBRIDGE, Mass.–(BUSINESS WIRE)–#NEJM—Bristol-Myers Squibb Company (NYSE:BMY) and Acceleron Pharma Inc. (NASDAQ:XLRN) today announced that the New England Journal of Medicine (NEJM) has published results from BELIEVE, the pivotal Phase 3 study evaluating the safety and efficacy of Reblozyl (luspatercept-aamt) for the treatment of anemia in adults with beta thalassemia who require regular red blood cell (RBC) transfusions.

“These results published in the New England Journal of Medicine demonstrate the clinical benefit of Reblozyl, the first approved treatment for anemia in beta thalassemia in the U.S.,” said Diane McDowell, M.D., vice president, Hematology Global Medical Affairs, Bristol Myers Squibb. “Patients with beta thalassemia experience chronic anemia, often requiring life-long treatment with red blood cell transfusions, which are associated with multiple medical complications.¹ The ability of Reblozyl to reduce the frequency and burden of regular red blood cell transfusions is clinically meaningful for these patients.”

In the BELIEVE trial, a significantly higher proportion of patients achieved a >33% reduction in RBC transfusion burden from baseline (with a reduction of at least two units) during weeks 13-24 when treated with Reblozyl compared to placebo, meeting the study’s primary endpoint. The study also met all key secondary endpoints with a significantly greater proportion of patients receiving Reblozyl compared to placebo achieving a >33% reduction in RBC transfusion burden during weeks 37-48 and a >50% reduction during weeks 13-24 or weeks 37-48.²

The most common adverse events (AEs) of any grade in greater than 5% of the Reblozyl treatment group compared to placebo were bone pain (19.7% vs. 8.3%), arthralgia (19.3% vs. 11.9%), dizziness (11.2% vs. 4.6%), hypertension (8.1% vs. 2.8%) and hyperuricemia (7.2% vs 0%). Grade >3 treatment emergent AEs were reported in a greater proportion of patients receiving Reblozyl compared to placebo (29.1% vs. 15.6%). The most common Grade >3 AEs reported with Reblozyl were anemia (3.1% vs. 0%), increased liver iron concentration (2.7% vs. 0.9%) and hyperuricemia (2.7% vs. 0%) compared to placebo, respectively. Serious adverse events were reported in 15.2% of patients receiving Reblozyl and 5.5% of patients receiving placebo.²

“We could not be more proud that the New England Journal of Medicine has chosen to publish data from two pivotal studies of Reblozyl, beginning this past January with the publication of the MEDALIST trial results in a population of patients with myelodysplastic syndromes,” said Habib Dable, President and Chief Executive Officer, Acceleron. “With today’s publication of data from the BELIEVE trial in a set of patients with beta thalassemia, we are confident that physicians and patients will become increasingly aware of a potential new treatment for severe anemia associated with two diseases of high unmet medical need.”

Results from BELIEVE supported the U.S. Food and Drug Administration (FDA) approval of Reblozyl for the treatment of anemia in adult patients with beta thalassemia who require regular RBC transfusions in November 2019, and were previously presented at the 60^th American Society of Hematology (ASH) Annual Meeting and Exposition in December 2018. Longer-term analyses from BELIEVE were presented at the 61^st ASH Annual Meeting in December 2019.

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

About BELIEVE

BELIEVE is a Phase 3, randomized, double-blind, placebo-controlled multicenter study comparing REBLOZYL plus best supportive care (BSC) versus placebo plus BSC in adults who require regular RBC transfusions (6-20 RBC units per 24 weeks with no transfusion-free period greater than 35 days during that period) due to beta thalassemia.² Best supportive care included RBC transfusions; iron-chelating agents; use of antibiotic, antiviral, and antifungal therapy; and/or nutritional support as needed.²

Bristol Myers Squibb: Advancing Cancer Research

At Bristol Myers Squibb, patients are at the center of everything we do. The goal of our cancer research is to increase quality, long-term survival and make cure a possibility. We harness our deep scientific experience, cutting-edge technologies and discovery platforms to discover, develop and deliver novel treatments for patients.

Building upon our transformative work and legacy in hematology and Immuno-Oncology that has changed survival expectations for many cancers, our researchers are advancing a deep and diverse pipeline across multiple modalities. In the field of immune cell therapy, this includes registrational chimeric antigen receptor (CAR) T-cell agents for numerous diseases, and a growing early-stage pipeline that expands cell and gene therapy targets, and technologies. We are developing cancer treatments directed at key biological pathways using our protein homeostasis platform, a research capability that has been the basis of our approved therapies for multiple myeloma and several promising compounds in early to mid-stage development. Our scientists are targeting different immune system pathways to address interactions between tumors, the microenvironment and the immune system to further expand upon the progress we have made and help more patients respond to treatment. Combining these approaches is key to delivering new options for the treatment of cancer and addressing the growing issue of resistance to immunotherapy. We source innovation internally, and in collaboration with academia, government, advocacy groups and biotechnology companies, to help make the promise of transformational medicines a reality for patients.

About Reblozyl^®(luspatercept-aamt)

Reblozyl is an erythroid maturation agent that promoted late-stage red blood cell maturation in animal models.³Bristol Myers Squibb and 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. Reblozyl is not indicated for use as a substitute for red blood cell transfusions in patients who require immediate correction of anemia.

A Biologics License Application for Reblozyl for the treatment of anemia in adults with very low- to intermediate-risk myelodysplastic syndromes (MDS) who have ring sideroblasts (MDS-RS) and who require regular red blood cell transfusions is currently under FDA review with a Prescription Drug User Fee Act (PDUFA), or target action, date of April 4, 2020. In Europe, Bristol Myers Squibb’s Marketing Authorization Application for the treatment of anemia in adults with beta thalassemia and MDS is currently under review.

Additional Clinical Investigation

A Phase 2 trial (BEYOND) in adult patients with non-transfusion-dependent beta thalassemia⁴; a Phase 2 trial in pediatric patients with transfusion-dependent beta thalassemia⁵; a Phase 3 trial (COMMANDS) in erythropoiesis-stimulating agent-naïve, lower-risk MDS patients⁶; and a Phase 2 trial in myelofibrosis patients are ongoing.⁷ The companies are also planning a Phase 3 trial known as INDEPENDENCE in myelofibrosis in 2020. For more information, please visit www.clinicaltrials.gov.

Indication

REBLOZYL is indicated for the treatment of anemia in adult patients with beta thalassemia who require regular red blood cell (RBC) transfusions.

REBLOZYL is not indicated for use as a substitute for RBC 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 to 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 occurred in 3.6% of patients on REBLOZYL. Serious adverse reactions occurring in 1% of patients included cerebrovascular accident and deep vein thrombosis. A fatal adverse reaction occurred in 1 patient treated with REBLOZYL who died due to an unconfirmed case of acute myeloid leukemia (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%).

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 full Prescribing Information for REBLOZYL.

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.

About Acceleron

Acceleron is a biopharmaceutical company dedicated to the discovery, development, and commercialization of therapeutics to treat serious and rare diseases. Acceleron’s leadership in the understanding of TGF-beta superfamily biology and protein engineering generates innovative compounds that engage the body’s ability to regulate cellular growth and repair.

Acceleron focuses its research and development efforts in hematologic and pulmonary diseases. In hematology, Acceleron and its global collaboration partner, Bristol Myers Squibb, are co-promoting newly approved Reblozyl^® (luspatercept-aamt), the first and only approved erythroid maturation agent, in the United States and are developing luspatercept for the treatment of chronic anemia in myelodysplastic syndromes and myelofibrosis. Acceleron is developing sotatercept for the treatment of pulmonary arterial hypertension, having recently reported positive topline results of the Phase 2 PULSAR trial and actively enrolling patients in the Phase 2 SPECTRA trial.

For more information, please visit www.acceleronpharma.com. Follow Acceleron on Social Media: @AcceleronPharma and LinkedIn.

Bristol-Myers Squibb Cautionary Statement Regarding Forward-Looking Statements

This press release contains “forward-looking statements” within the meaning of the Private Securities Litigation Reform Act of 1995 regarding, among other things, the research, development and commercialization of pharmaceutical products. All statements that are not statements of historical facts are, or may be deemed to be, forward-looking statements. Such forward-looking statements are based on historical performance and current expectations and projections about our future financial results, goals, plans and objectives and involve inherent risks, assumptions and uncertainties, including internal or external factors that could delay, divert or change any of them in the next several years, that are difficult to predict, may be beyond our control and could cause our future financial results, goals, plans and objectives to differ materially from those expressed in, or implied by, the statements. These risks, assumptions, uncertainties and other factors include, among others, that future study results will be consistent with the results to date, that Reblozyl (luspatercept-aamt) will be successfully commercialized for the indication for which it is currently approved, that Reblozyl may not achieve its primary study endpoints or receive regulatory approval for the additional indications described in this release in the currently anticipated timeline or at all and, if approved, whether such product candidate for such additional 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, 2018, as updated by our subsequent Quarterly Reports on Form 10-Q, Current Reports on Form 8-K and other filings with the Securities and Exchange Commission. The forward-looking statements included in this document are made only as of the date of this document and except as otherwise required by applicable law, Bristol-Myers Squibb undertakes no obligation to publicly update or revise any forward-looking statement, whether as a result of new information, future events, changed circumstances or otherwise.

Acceleron Pharma Cautionary Statement Regarding Forward-Looking Statements

This press release contains forward-looking statements about Acceleron’s strategy, future plans and prospects, including statements regarding the development and commercialization of Acceleron’s compounds, the timeline for clinical development and regulatory approval of Acceleron’s compounds, the expected timing for reporting of data from ongoing clinical trials, and the potential of REBLOZYL^® (luspatercept-aamt) as a therapeutic drug. The words “anticipate,” “believe,” “could,” “estimate,” “expect,” “goal,” “intend,” “may,” “plan,” “potential,” “project,” “should,” “target,” “will,” “would,” and similar expressions are intended to identify forward-looking statements, although not all forward-looking statements contain these identifying words.

Actual results could differ materially from those included in the forward-looking statements due to various factors, risks and uncertainties, including, but not limited to, that the results of any clinical trials may not be predictive of the results or success of other clinical trials, that regulatory approval of Acceleron’s compounds in one indication or country may not be predictive of approval in another indication or country, that the development of Acceleron’s compounds will take longer and/or cost more than planned, that Acceleron or its collaboration partner, BMS, will be unable to successfully complete the clinical development of Acceleron’s compounds, that Acceleron or BMS may be delayed in initiating, enrolling or completing any clinical trials, and that Acceleron’s compounds will not receive regulatory approval or become commercially successful products. These and other risks and uncertainties are identified under the heading “Risk Factors” included in Acceleron’s most recent Annual Report on Form 10-K, and other filings that Acceleron has made and may make with the SEC in the future.

The forward-looking statements contained in this press release are based on management’s current views, plans, estimates, assumptions, and projections with respect to future events, and Acceleron does not undertake and specifically disclaims any obligation to update any forward-looking statements.

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 2019.

² Cappellini, M.D., Phase 3 Study of Luspatercept for B-Thalassemia Requiring Transfusion. New England Journal of Medicine.

³ REBLOZYL U.S. Prescribing Information. Accessed February 2020.

⁴ ClinicalTrials.gov. A Study to Determine the Efficacy and Safety of Luspatercept in Adults With Non Transfusion Dependent Beta (β)-Thalassemia (BEYOND). Available at: https://www.clinicaltrials.gov/ct2/show/NCT03342404?term=BEYOND&cond=Beta-Thalassemia&rank=2. Accessed February 2020

⁵ ClinicalTrials.gov. Study of Safety & PK of Luspatercept (ACE-536) in Pediatric Subjects Who Require Regular RBC Transfusions Due to Beta (β)-Thalassemia. Available at: https://clinicaltrials.gov/ct2/show/NCT04143724?term=luspatercept%2C+beta+thalassemia%2C+pediatric&draw=2&rank=1. Accessed February 2020.

⁶ ClinicalTrials.gov. Efficacy and Safety Study of Luspatercept (ACE-536) Versus Epoetin Alfa for the Treatment of Anemia Due to IPSS-R Very Low, Low or Intermediate Risk Myelodysplastic Syndromes (MDS) in ESA Naïve Subjects Who Require Red Blood Cell Transfusions (COMMANDS). Available at: https://www.clinicaltrials.gov/ct2/show/NCT03682536?term=COMMANDS+luspatercept&rank=1. Accessed February 2020.

⁷ ClinicalTrials.gov. A Safety and Efficacy Study to Evaluate Luspatercept in Subjects With Myeloproliferative Neoplasm-associated Myelofibrosis Who Have Anemia With and Without Red Blood Cell-transfusion Dependence. Available at: https://www.clinicaltrials.gov/ct2/show/NCT03194542?term=luspatercept&cond=Myelofibrosis&rank=1. Accessed February 2020.