Applications based on results from Phase 3 COMMANDS study in which first-in-class Reblozyl demonstrated a highly statistically significant and clinically meaningful improvement compared to an erythropoiesis-stimulating agent in patients with very low/low/intermediate-risk MDS

U.S. FDA has assigned a target action date of August 28, 2023

PRINCETON, N.J.--(BUSINESS WIRE)-- Bristol Myers Squibb (NYSE: BMY) today announced that the U.S. Food and Drug Administration (FDA) has accepted the supplemental Biologics License Application (sBLA) and the European Medicines Agency (EMA) has validated the Type II Variation Application for Reblozyl® (luspatercept-aamt), a first-in-class treatment option, to expand its current indication to include treatment of anemia without previous use of erythropoiesis-stimulating agents (ESA-naïve) in adult patients with very low- to intermediate-risk myelodysplastic syndromes (MDS) who may require red blood cell (RBC) transfusions. In the U.S., the FDA has granted the application Priority Review and assigned a Prescription Drug User Fee Act (PDUFA) goal date of August 28, 2023. Priority Review designation underscores the high unmet need and value that Reblozyl could bring to this patient population. In Europe, the EMA’s validation of the application confirms the submission is complete and begins the EMA’s centralized review process.

“Initial treatment options for very low- to intermediate-risk myelodysplastic syndromes, including erythropoiesis-stimulating agents, can alleviate anemia in some patients but others will either not respond or become resistant to therapy, and additional therapy options have remained urgently needed,” said Noah Berkowitz, M.D., Ph.D., senior vice president, Hematology Development, Bristol Myers Squibb. “Results from the COMMANDS study showed Reblozyl significantly improved transfusion independence and elevated hemoglobin compared to ESA therapy epoetin alfa. Reblozyl is an important option available for the treatment of anemia in patients with transfusion-dependent, lower-risk MDS who have experienced ESA failure, and we look forward to working with the FDA and EMA to expand its potential use as a first-line therapy in eligible patients.”

The submissions are based on results from the COMMANDS study, a Phase 3, open-label, randomized trial evaluating Reblozyl versus epoetin alfa, an ESA, for the treatment of anemia in adult patients with very low-, low- or intermediate-risk MDS who require RBC transfusions and are ESA-naïve. Results demonstrated a highly statistically significant and clinically meaningful improvement in red blood cell transfusion independence (RBC-TI) for ≥12 weeks with concurrent hemoglobin (Hb) increase (≥1.5 g/dL) in the first-line treatment of adult patients with very low-, low- or intermediate-risk MDS who require RBC transfusions. Safety results in the trial were consistent with the safety profile of Reblozyl for the treatment of anemia in adult patients with low-risk MDS who require regular RBC transfusions, observed in previous clinical trials as well as in the post-marketing setting.

Full results from the COMMANDS study will be presented at upcoming medical meetings. Reblozyl is being developed and commercialized through a global collaboration with Merck following Merck’s acquisition of Acceleron Pharma, Inc. in November 2021.

About COMMANDS

COMMANDS (NCT03682536) is a Phase 3, open-label, randomized study evaluating the efficacy and safety of Reblozyl versus epoetin alfa for the treatment of anemia due to very low-, low- or intermediate-risk (IPSS-R) myelodysplastic syndromes (MDS) in patients who are red blood cell (RBC) transfusion-dependent and were erythropoiesis-stimulating agent (ESA)-naïve.

The primary endpoint evaluated in this study is red blood cell transfusion independence (RBC-TI) for 12 weeks with a mean hemoglobin (Hb) increase ≥1.5 g/dL. Key secondary endpoints include RBC-TI for 24 weeks, RBC-TI ≥12 weeks and erythroid response of at least 8 weeks during weeks 1-24 of the study.

About MDS

Myelodysplastic syndromes (MDS) are a group of closely related blood cancers characterized by ineffective production of healthy red blood cells (RBC), white blood cells and platelets, which can lead to anemia and frequent or severe infections.1,2 People with MDS who develop anemia often require regular blood transfusions to increase the number of healthy red blood cells in circulation.3 Frequent transfusions are associated with an increased risk of iron overload, transfusion reactions and infections.4 Patients who become RBC transfusion-dependent have a significantly shorter overall survival than those who are not dependent on transfusions, partially due to iron overload or to more severe bone marrow disease than in non-transfusion-dependent patients.5

About Reblozyl® (luspatercept-aamt)

Reblozyl, a first-in-class therapeutic option, promotes late-stage red blood cell maturation in animal models.6 Reblozyl is being developed and commercialized through a global collaboration with Merck following Merck’s acquisition of Acceleron Pharma, Inc. in November 2021. 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 syndromes 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. In the U.S., Reblozyl is not indicated for use in patients with non-transfusion-dependent beta thalassemia.

U.S. Important Safety Information

WARNINGS AND PRECAUTIONS

Thrombosis/Thromboembolism

In adult patients with beta thalassemia, thromboembolic events (TEE) were reported in 8/223 (3.6%) of 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. In adult patients with MDS with normal baseline blood pressure, 26 (29.9%) patients developed SBP ≥130 mm Hg and 23 (16.4%) patients developed DBP ≥80 mm Hg. Monitor blood pressure prior to each administration. Manage new or exacerbations of preexisting hypertension using anti-hypertensive agents.

Extramedullary Hematopoietic Masses

In adult patients with transfusion-dependent beta thalassemia, EMH masses were observed in 3.2% of REBLOZYL-treated patients, with spinal cord compression symptoms due to EMH masses occurring in 1.9% of patients (BELIEVE and REBLOZYL long-term follow-up study).

In a study of adult patients with non-transfusion-dependent beta thalassemia, a higher incidence of EMH masses was observed in 6.3% of REBLOZYL-treated patients vs. 2% of placebo-treated patients in the double- blind phase of the study, with spinal cord compression due to EMH masses occurring in 1 patient with a prior history of EMH. REBLOZYL is not indicated for use in patients with non-transfusion-dependent beta thalassemia.

Possible risk factors for the development of EMH masses in patients with beta thalassemia include history of EMH masses, splenectomy, splenomegaly, hepatomegaly, or low baseline hemoglobin (