PRINCETON, N.J. — Bristol Myers Squibb (NYSE: BMY) today announced the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) has recommended approval of Reblozyl® (luspatercept) as a treatment for adult patients with transfusion-dependent anemia due to very low, low and intermediate-risk myelodysplastic syndromes (MDS). The recommendation will now be reviewed by the European Commission (EC), which has the authority to approve medicines for the European Union (EU). Upon approval, this would represent the fourth authorized indication for Reblozyl in the EU.
The CHMP adopted a positive opinion based on results from the pivotal Phase 3 COMMANDS trial. Results from the primary analysis showed 60.4% (n=110) of patients treated with Reblozyl vs. 34.8% (n=63) of patients treated with epoetin alfa achieved the primary endpoint of red blood cell (RBC) transfusion independence of at least 12 weeks with a mean hemoglobin increase of at least 1.5 g/dL within the first 24 weeks (p<0.0001). Safety results were consistent with previous MDS studies and were in line with expected symptoms in this patient population.
“The positive recommendation by CHMP for Reblozyl can provide an important first-line treatment option for patients with lower-risk MDS in Europe,” said Anne Kerber, M.D., senior vice president, Head of Late Clinical Development, Hematology, Oncology, Cell Therapy (HOCT), Bristol Myers Squibb. “Current treatments, including erythropoiesis stimulating agents, provide limited benefit against anemia. Results from the head-to-head COMMANDS study show that Reblozyl delivered transfusion independence in nearly twice the number of patients compared with epoetin alfa, and with a longer duration of response.”
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 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.
At the time of the primary analysis (March 31, 2023), 363 patients were randomized 1:1 to Reblozyl and epoetin alfa. Results from the primary analysis of the intent to treat (ITT) population showed:
- 60.4% (n=110) of patients receiving Reblozyl vs. 34.8% (n=63) 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 74.2% (n=135) of Reblozyl patients vs. 53% (n=96) of epoetin alfa patients (p<0.0001).
- RBC-TI of at least 12 weeks was achieved by 68.1% (n=124) of Reblozyl patients vs. 48.6% (n=88) of epoetin alfa patients (p<0.0001).
- Duration of response was 128.1 weeks (108.3-NE) for Reblozyl in patients who achieved TI for at least 12 weeks (achieved weeks 1-24) compared to 89.7 weeks (55.9-157.3) for epoetin alfa (Hazard Ratio [HR]: 0.534; 95% Confidence Interval [CI]: 0.330-0.864, p=0.0096).
Safety results were consistent with previous MDS studies, and progression to acute myeloid leukemia and total deaths were similar between both arms of the study. The most common treatment-emergent adverse events in at least 10% of patients were diarrhea, fatigue, COVID-19, hypertension, dyspnea, nausea, peripheral edema, asthenia, dizziness, anemia, back pain and headache. Rates of reported fatigue and asthenia were shown to decrease over time.
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. People with MDS who develop anemia often require blood transfusions to increase the number of healthy RBCs in circulation. Frequent transfusions are associated with an increased risk of iron overload, transfusion reactions and infections. 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.
About Reblozyl® (luspatercept)
REBLOZYL, a first-in-class therapeutic option, promotes expansion and maturation of late-stage red blood cells in animal models. Reblozyl is being developed and commercialized through a global collaboration and North American co-promotion with Merck following Merck’s acquisition of Acceleron Pharma, Inc. in November 2021.
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.
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