Data from MEDALIST showed significant clinical benefit of Reblozyl in treating anemia in adults with myelodysplastic syndromes
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 MEDALIST, the pivotal phase 3 study evaluating the use of Reblozyl® (luspatercept-aamt) to treat anemia in patients with very low- to intermediate-risk myelodysplastic syndromes (MDS) who have ring sideroblasts (RS+) and require red blood cell transfusions, and who had failed, were intolerant to, or ineligible for/unlikely to respond to treatment with erythropoiesis-stimulating agents (ESAs).1
"This NEJM publication recognizes the importance and robustness of the MEDALIST study, as well as the impact and potential clinical benefit of Reblozyl in MDS patients who have ring sideroblasts," said Diane McDowell, M.D., Vice President, Hematology Global Medical Affairs, Bristol-Myers Squibb. "As the first erythroid maturation agent, Reblozyl holds the potential to help these patients address the underlying cause of their disease-related chronic anemia."
MEDALIST achieved a statistically significant improvement in the primary endpoint of red blood cell transfusion independence (RBC-TI) for 8 or more weeks during the first 24 weeks of the study. The study also met the key secondary endpoint of RBC-TI for 12 or more weeks during the first 24 or 48 weeks of the study, as well as the additional secondary endpoint of hematologic improvement-erythroid (HI-E) for 8 or more weeks as assessed by International Working Group 2006 criteria.1
The most common treatment-emergent adverse events (TEAEs) of any grade in greater than 10% of patients in either the treatment or placebo arm were fatigue, diarrhea, asthenia, nausea, dizziness, and back pain. TEAEs of Grade 3 or 4 were reported in 42.5% (65/153) of patients receiving luspatercept-aamt and 44.7% (34/76) of patients receiving placebo. Progression to acute myeloid leukemia (AML) occurred in three patients (2.0%) receiving luspatercept-aamt and one patient (1.3%) receiving placebo. Five patients receiving luspatercept-aamt (3.3%) and four patients receiving placebo (5.3%) experienced one or more TEAE that resulted in death.1
Results from MEDALIST were initially presented during the Plenary Scientific Session at the 60th American Society of Hematology (ASH) Annual Meeting and Exposition in December 2018. Longer-term analyses from MEDALIST were recently presented at the 61st ASH Annual Meeting in December 2019.
"It is truly an honor to see work that began in Acceleron laboratories more than a decade ago and advanced successfully through a collaboration with Bristol-Myers Squibb now highlighted in the New England Journal of Medicine," said Habib Dable, President and Chief Executive Officer of Acceleron. "Publication of the MEDALIST trial results in a journal of such eminence will certainly help to raise awareness among physicians of a potential new therapeutic option for treating anemia in certain patients with MDS."
The U.S. Food and Drug Administration (FDA) is evaluating Reblozyl for the treatment of anemia in adults with very low- to intermediate-risk MDS who have ring sideroblasts and require red blood cell transfusions, and has set a Prescription Drug User Fee Act (PDUFA), or target action, date of April 4, 2020 for this indication. 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.
In November 2019, Reblozyl was granted approval by the FDA to treat 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.
Reblozyl is not approved to treat MDS in any geography.
MEDALIST is a phase 3, randomized, double blind, placebo-controlled, multi-center study evaluating the safety and efficacy of luspatercept in patients with IPSS-R-defined very low-, low-, or intermediate-risk non-del(5q) myelodysplastic syndromes (MDS). All patients were red blood cell transfusion-dependent and were either refractory or intolerant to prior ESA therapy, or were ESA naïve and unlikely to respond due to endogenous serum erythropoietin levels of ≥ 200 U/L, and had no prior treatment with disease modifying agents.
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.2 Bristol-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.
Additional Clinical Investigation
A phase 2 trial (BEYOND) in adult patients with non-transfusion-dependent beta thalassemia3; a phase 2 trial in pediatric patients with transfusion-dependent beta thalassemia4; a phase 3 trial (COMMANDS) in ESA-naïve, lower-risk MDS patients5; and a phase 2 trial in myelofibrosis patients are ongoing.6 The companies are also planning a phase 3 trial known as INDEPENDENCE in myelofibrosis in 2020. For more information, please visit www.clinicaltrials.gov.
Reblozyl has not been approved as safe and effective for use in patients with MDS or myelofibrosis in any country.
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
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 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.
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.
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
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
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.
Acceleron is a biopharmaceutical company dedicated to the discovery, development, and commercialization of therapeutics to treat serious and rare diseases. The Company'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, neuromuscular, 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 also advancing its neuromuscular program with ACE-083, a locally-acting Myostatin+ agent in Phase 2 development in Charcot-Marie-Tooth disease and is conducting a Phase 2 pulmonary program with sotatercept in pulmonary arterial hypertension.
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.
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 preclinical testing of Acceleron’s compounds and data from clinical trials may not be predictive of the results or success of ongoing or later clinical trials, 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.
1 Fenaux P. Luspatercept in Patients with Lower-Risk Myelodysplastic Syndromes. New England Journal of Medicine.
2 REBLOZYL U.S. Prescribing Information. Accessed November 2019.
3 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 October 2019.
4 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 December 2019.
5 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 October 2019.
6 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 October 2019.
Bristol-Myers Squibb Company
Acceleron Pharma Inc.
Todd James, IRC, (617) 649-9393
Vice President, Investor Relations and Corporate Communications
Ed Joyce, (617) 649-9242
Director, Investor Relations
Matt Fearer, (617) 301-9557
Director, Corporate Communications