U.S. FDA Approves Bristol Myers Squibb’s Reblozyl® (luspatercept-aamt) as First-Line Treatment of Anemia in Adults with Lower-Risk Myelodysplastic Syndromes (MDS) Who May Require Transfusions

Bristol Myers Squibb (NYSE: BMY) today announced that the U.S. Food and Drug Administration (FDA) has approved Reblozyl® (luspatercept-aamt) for the treatment of anemia without previous erythropoiesis stimulating agent use (ESA-naïve) in adult patients with very low- to intermediate-risk myelodysplastic syndromes (MDS) who may require regular red blood cell (RBC) transfusions. This expanded indication to the first-line setting is based on interim results from the pivotal Phase 3 COMMANDS trial, in which Reblozyl demonstrated superior efficacy of concurrent RBC transfusion independence (RBC-TI) and hemoglobin (Hb) increase compared to epoetin alfa, an ESA, regardless of ring sideroblast status. These results underscore Reblozyl’sability to address chronic anemia earlier in the treatment journey in a broader range of patients.

“For patients with lower-risk MDS, current standard therapies, including ESAs, have provided limited benefit in controlling anemia with only 1 in 3 patients responding for a duration of 6-18 months,” said Guillermo Garcia-Manero, M.D., lead investigator and Chief of the Section of Myelodysplastic Syndromes at The University of Texas MD Anderson Cancer Center. “Results from the COMMANDS study showed nearly twice as many patients treated with Reblozyl achieved transfusion independence of at least 12 weeks and concurrent hemoglobin increase compared to epoetin alfa. Today’s approval represents an important advancement for patients with lower-risk MDS.”

In the Phase 3 COMMANDS trial, results showed 58.5% (n=86) of patients treated with Reblozyl vs. 31.2% (n=48) of patients treated with epoetin alfa achieved the primary endpoint of RBC-TI of at least 12 weeks with a mean Hb increase of at least 1.5 g/dL within the first 24 weeks (p<0.0001). The most common (>10%) adverse reactions were diarrhea, fatigue, hypertension, peripheral edema, nausea, and dyspnea.

“Today’s expanded approval of Reblozyl marks an important milestone in our commitment to MDS patients with anemia by providing a durable and more effective treatment option, with more convenient and less frequent administration,” said Wendy Short-Bartie, senior vice president and general manager, U.S. Hematology and Cell Therapy, Bristol Myers Squibb. “We remain dedicated to addressing hard-to-treat diseases with significant burden to patients and look forward to bringing this important option earlier in the treatment process.”

“The majority of patients with MDS experience chronic anemia and require RBC transfusions,” said Tracey Iraca, executive director, MDS Foundation. “The approval of Reblozyl in the first-line treatment of anemia for patients with lower-risk MDS represents a crucial step in making transfusion independence possible for more patients.”

Results from the COMMANDS study were featured in June as part of the press program at the American Society of Clinical Oncology (ASCO) Annual Meeting and plenary session at the European Hematology Association (EHA) Congress, with simultaneous publication in The Lancet. Reblozyl is being developed and commercialized through a global collaboration with Merck as of November 2021.

COMMANDS Study Results
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 syndrome (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 RBC transfusion independence (RBC-TI) for 12 weeks with a mean hemoglobin (Hb) increase ≥1.5 g/dL. Key secondary endpoints include erythroid response (HI-E) of at least 8 weeks during weeks 1-24 of the study, RBC-TI ≥12 weeks and RBC-TI for 24 weeks. Eligible patients were ≥18 years old with lower-risk MDS who require transfusions. Patients were randomized 1:1 to receive subcutaneous Reblozyl (starting dose 1.0 mg/kg, titration up to 1.75 mg/kg) once every 3 weeks or epoetin alfa (starting dose 450 IU/kg, titration up to 1050 IU/kg) weekly for ≥24 weeks. The majority of study participants (>90%) were outside of the United States and a non-U.S.-licensed epoetin alfa product was used in the control arm for such patients.

At the time of the planned interim analysis (October 31, 2022), 147 evaluable patients received Reblozyl and 154 evaluable patients received epoetin alfa, with median treatment durations of 41.6 and 27 weeks, respectively. Results published in The Lancetshowed:

  • 58.5% (n=86) of patients receiving Reblozyl vs. 31.2% (n=48) of patients receiving epoetin alfa achieved the primary endpoint of RBC-TI of at least 12 weeks with concurrent mean Hb increase of at least 1.5 g/dL within the first 24 weeks (p<0.0001).
  • HI-E increase of at least 8 weeks was achieved by 74.1% (n=109) of Reblozyl patients vs. 51.3% (n=79) of epoetin alfa patients (p<0.0001).
  • Within the first 24 weeks of treatment, RBC-TI of at least 24 weeks was achieved by 47.6% (n=70) of Reblozyl patients vs. 29.2% (n=45) of epoetin alfa patients (p=0.0012).
  • RBC-TI of at least 12 weeks was achieved by 66.7% (n=98) of Reblozyl patients vs. 46.1% (n=71) of epoetin alfa patients (p=0.0003).

Patients treated with Reblozyl demonstrated durable responses with nearly 2.5 years of median RBC-TI ≥12 weeks (126.6 weeks, week 1 to end of treatment). The most common (>10%) adverse reactions were diarrhea, fatigue, hypertension, peripheral edema, nausea, and dyspnea.

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