Bristol Myers Squibb to Present First Results at ASCO and EHA from Phase 3 COMMANDS Study of Reblozyl® (luspatercept-aamt) in First-Line Treatment of Anemia in Adults with Lower-Risk Myelodysplastic Syndromes (MDS)

Results from Phase 3 COMMANDS study, selected for ASCO’s official press program, show nearly twice as many patients treated with Reblozyl achieved superior transfusion independence with concurrent hemoglobin increase vs. epoetin alfa, including in clinically relevant subgroups

Reblozyl demonstrated a durable response, with nearly 2.5 years median transfusion independence, 1 year longer than epoetin alfa

Additional results, to be presented during the plenary session at the European Hematology Association Congress, show Reblozyl demonstrated clinical benefit across patients with spectrum of MDS mutations

PRINCETON, NJ, USA I May 25, 2023 I Bristol Myers Squibb (NYSE: BMY) today announced first results from the Phase 3 COMMANDS study, an open-label, randomized trial evaluating Reblozyl^® (luspatercept-aamt) versus epoetin alfa, an erythropoiesis-stimulating agent (ESA), for the treatment of anemia in adult patients with very low-, low- or intermediate-risk myelodysplastic syndromes (MDS) who require red blood cell (RBC) transfusions and are ESA-naïve. Results from the study will be featured as part of the press program at the American Society of Clinical Oncology (ASCO) Annual Meeting on June 2, 3 p.m. EDT (Abstract #7003), and in an oral presentation of select abstracts during a plenary session at the European Hematology Association (EHA) Congress on June 10, 2:45 p.m. CEST (Abstract #S102).

“Chronic anemia, low hemoglobin levels and transfusion dependency are the primary clinical challenges for patients with lower-risk MDS, increasing the risk of death by more than half compared to those who do not require transfusions,” 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 treatment with Reblozyl compared to epoetin alfa led to superior and statistically significant improvements in red blood cell transfusion independence and hemoglobin increase, improvements in response durability, and equal or better outcomes across all subgroups, with acceptable safety and tolerability for patients with ESA-naïve, lower-risk MDS.”

The primary endpoint evaluated in the COMMANDS study is RBC transfusion independence (RBC-TI) for 12 weeks with a mean hemoglobin increase of ≥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.

COMMANDS Study Results at ASCO
At the time of the interim analysis, 147 evaluable patients received Reblozyl and 154 evaluable patients received epoetin alfa, with median treatment durations of 41.6 and 27 weeks, respectively. Results showed 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 hemoglobin (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). Patients treated with Reblozyl achieved more durable responses vs. epoetin alfa, with a median duration of response of RBC-TI ≥12 weeks (Week 1 to end of treatment) of 126.6 vs. 77 weeks. 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=0.0006). Benefit with Reblozyl was also observed in clinically relevant subgroups, and results showed a consistent safety profile and no new safety signals.

COMMANDS Study Results at EHA
Data to be presented at EHA included both efficacy and safety consistent with results at ASCO, and showed Reblozyl demonstrated favorable outcomes compared to epoetin alfa across common MDS mutations (SF3B1, SF3B1a, ASXL1, TET2, DNMT3A, EZH2, IDH2, U2AF1) and had a higher probability of achieving clinical benefit, regardless of overall mutational burden.

A supplemental Biologics License Application for Reblozyl is currently under Priority Review with the U.S. Food and Drug Administration (FDA) for treatment of anemia in ESA-naïve adult patients with very low- to intermediate-risk MDS who may require RBC transfusions with an assigned Prescription Drug User Fee Act (PDUFA) goal date of August 28, 2023. The European Medicines Agency has also validated the Type II Variation for Reblozyl in this patient population. Reblozyl is being developed and commercialized through a global collaboration with Merck following Merck’s acquisition of Acceleron Pharma, Inc. in November 2021.

“Clinical experience has demonstrated that just one in three patients with low-risk myelodysplastic syndromes experience responses to erythroid stimulating agents over 6-18 months, leaving a significant need for more effective options to address chronic anemia,” said Matteo Giovanni Della Porta, study investigator and head of Leukemia Unit at Humanitas Cancer Center in Milan, Italy. “In the COMMANDS study, the median duration of red blood cell transfusion independence was nearly one year longer with Reblozyl than with epoetin alfa and showed safety consistent with its known profile, demonstrating its potential as a first-line treatment in patients with transfusion-dependent, very low- to intermediate-risk MDS.”

“Results being presented at ASCO and EHA reinforce the notion that Reblozyl should be used as the initial treatment of anemia in patients with lower- to intermediate-risk myelodysplastic syndromes,” said Noah Berkowitz, M.D., Ph.D., senior vice president, Hematology Development, Bristol Myers Squibb. “As a potentially more effective and durable upfront treatment option, Reblozyl could shift the paradigm for standard of care among these patients.”

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 syndrome 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.

Please see full Prescribing Information and Summary of Product Characteristics for REBLOZYL.

Bristol Myers Squibb: Creating a Better Future for People with Cancer

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References:

1. Mount Sinai. Myelodysplastic Syndrome. Available at: https://www.mountsinai.org/care/cancer/services/mds. Accessed March 2023.
2. Myelodysplastic Syndromes Foundation. What is MDS? Available at: https://www.cancer.org/cancer/myelodysplastic-syndrome/about/what-is-mds.html. Accessed March 2023.
3. Johns Hopkins Medicine. Myelodysplastic Syndrome. Available at: https://www.hopkinsmedicine.org/kimmel_cancer_center/types_cancer/myelodysplastic_syndrome.html. Accessed March 2023.
4. Rasel M, Mahboobi SK. Transfusion Iron Overload. PubMed. 2021. Available at: https://www.ncbi.nlm.nih.gov/books/NBK562146/. Accessed March 2023.
5. Triantafyllidis I, Ciobanu A, Stanca O, Lupu AR. Prognostic factors in myelodysplastic syndromes. Maedica (Bucur). 2012 Dec;7(4):295-302. Available at: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3593279. Accessed March 2023.
6. Galanello R, Origa R. Beta thalassemia. Orphanet Journal of Rare Diseases. 2010;5(11). Available at: https://ojrd.biomedcentral.com/articles/10.1186/1750-1172-5-11. Accessed March 2023.

SOURCE: Bristol Myers Squibb