7 April 2020 - - The US Food and Drug Administration has approved Reblozyl (luspatercept-aamt), the first and only erythroid maturation agent, for the treatment of anemia failing an erythropoiesis stimulating agent and requiring two or more red blood cell units over eight 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), US-based pharmaceutical company Bristol Myers Squibb (NYSE: BMY) and Acceleron Pharma Inc. (NASDAQ: XLRN).

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

The FDA approval in MDS is based on results from the pivotal Phase 3 MEDALIST trial and marks the second indication for Reblozyl, which received its first approval in November 2019 for the treatment of anemia in adults with beta thalassemia who require regular RBC transfusions.

The approval of Reblozyl was based on the findings of MEDALIST, a Phase 3, randomized, double blind, placebo-controlled, multi-center study evaluating the efficacy and safety of Reblozyl in patients with IPSS-R-defined very low-, low- and intermediate-risk non-del(5q) myelodysplastic syndromes with ring sideroblasts.

All patients were red blood cell transfusion-dependent and were either refractory or intolerant to prior erythropoiesis-stimulating agent therapy or were ESA naïve and unlikely to respond due to endogenous serum erythropoietin ≥200 U/L, and had no prior treatment with disease modifying agents.

In the trial, a significantly greater proportion of patients receiving Reblozyl achieved independence from RBC transfusions for at least eight weeks during the first 24 weeks of the trial compared with those receiving placebo, meeting the study's primary endpoint.

Additionally, a significantly greater proportion of patients receiving Reblozyl vs. placebo achieved at least 12 weeks of independence from transfusions within the first 24 and 48 weeks of the study.

The majority of treatment-emergent adverse events (TEAEs) in the trial were Grade 1-2. Grade 3 or 4 treatment-emergent adverse events were reported in 42.5% of patients who received Reblozyl and 44.7% of patients who received placebo.

The most common all-grade adverse reactions included fatigue, musculoskeletal pain, dizziness, diarrhea, dyspnea, nausea, hypersensitivity reactions, headache, and upper respiratory tract infection.

Results from MEDALIST were published in the New England Journal of Medicine in January 2020.

Myelodysplastic syndromes are a group of closely related blood cancers characterized by ineffective production of healthy red blood cells, white blood cells and platelets, which can lead to anemia and frequent or severe infections.

People with MDS who develop anemia often require regular blood transfusions to increase the number of healthy red blood cells in circulation.4 Frequent transfusions are associated with an increased risk of iron overload, transfusion reactions and infections.

Reblozyl, the first and only erythroid maturation agent, promotes late-stage red blood cell maturation in animal models.1 Bristol Myers Squibb and Acceleron are jointly developing Reblozyl as part of a global collaboration. 

Reblozyl is currently approved in the US 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.

Reblozyl is indicated for the treatment of anemia in adult patients with beta thalassemia who require regular red blood cell transfusions

Reblozyl is indicated for the treatment of anemia failing an erythropoiesis stimulating agent and requiring 2 or more red blood cell units over eight 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 RBC transfusions in patients who require immediate correction of anemia

In adult patients with beta thalassemia, thromboembolic events were reported in 8/223 Reblozyl -treated patients.