Primary efficacy and safety analysis of the phase III COMMANDS trial of Reblozyl (luspatercept-aamt) for treatment of anemia in erythropoiesis stimulating agent-naïve patients with lower-risk myelodysplastic syndromes presented at ASH 2023.- BMS

These data are being presented in an oral presentation at the 2023 American Society of Hematology (ASH) Annual Meeting, from December 9-12.

“These data from the COMMANDS trial, including additional patients and longer follow-up from the data shown at ASCO, confirm the positive outcome of the interim analysis with superior efficacy and durability compared to ESAs and exemplify how Reblozyl may impact the treatment of anemia related to MDS,” 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. “Further, beyond the intent-to-treat population, the analysis confirms that Reblozyl demonstrated clinical benefit across subgroups.”

Results from COMMANDS are under review with the European Commission and served as the basis of a priority review approval by the FDA in August 2023 for Reblozyl as a treatment for anemia in ESA-naïve adult patients with very low- to intermediate-risk MDS who may require regular RBC transfusions. Reblozyl is being developed and commercialized through a global collaboration with Merck as of November 2021.

COMMANDS Primary Results : 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: i. 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 hemoglobin (Hb) increase of at least 1.5 g/dL within the first 24 weeks (p<0.0001). ii. erythroid response (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). iii. rbc transfusion independence (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). iv. duration of response was 126.6 weeks (99-ne) for reblozyl in patients who achieved ti for at least 12 weeks (achieved weeks 1-24) compared to 89.7 weeks (61.9-123.9) for epoetin alfa (hazard ratio [hr]: 0.586; 95% confidence interval [ci]: 0.380-0.904, p="0.0147)."></0.0001).></0.0001).></0.0001).>

“As patients with lower-risk MDS often receive limited benefit from current standard therapies, including ESAs, these confirmatory data further show how Reblozyl has the potential to create a paradigm shift in the treatment of anemia associated with this disease,” said Anne Kerber, senior vice president, Head of Late Clinical Development, Hematology, Oncology, Cell Therapy (HOCT), Bristol Myers Squibb.

Safety results were consistent with previous MDS studies , and progression to acute myeloid leukemia and total deaths were similar between 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.

In addition to the overall benefit observed in the ITT population, sub-analyses confirmed similar or greater RBC-TI of Reblozyl compared to epoetin alfa regardless of mutational profile, IPSS-M status, ring sideroblast status, transfusion burden and serum erythropoietin (sEPO) level. Duration of RBC-TI favored Reblozyl across all subgroups, including ring sideroblast status.

Finally, three posters will be presented highlighting additional analyses of the COMMANDS study and the mechanism of Reblozyl. i. Reblozyl showed favorability over epoetin alfa in various mutational background observed in lower-risk MDS in an analysis of response by mutational burden (Poster Presentation #4591). ii. An analysis of clonal-hematopoiesis related mutations (Poster Presentation #3214) showed that 85% of patients in the COMMANDS study had at least one CHIP-related mutation. Further, Reblozyl was associated with the downregulation of inflammatory gene signatures and upregulation of anti-inflammatory pathways .iii. In another analysis (Poster Presentation #1845), Reblozyl was associated with modulation of inflammation and restoration of effective erythropoiesis in bone marrow samples from the COMMANDS study, reinforcing its role in the expansion and maturation of early and late-stage erythroid precursors.