End Point Success Varies in a Phase 3 Trial of Luspatercept Plus JAK Inhibitor Therapy for MF Anemia

The INDEPENDENCE clinical trial has evaluated luspatercept-aamt plus Janus kinase (JAK) inhibitor therapy as an approach to treat myelofibrosis-associated anemia in adults. Bristol Myers Squibb announced in a press release that the combination did not meet the trial’s primary end point of producing red blood cell (RBC) transfusion independence.

In a global collaboration with Merck, Bristol Myers Squibb has developed and commercialized luspatercept-aamt as Reblozyl. In response to the INDEPENDENCE trial results, the company highlighted that luspatercept still accomplished clinically significant improvements of anemia in the study cohort.

“We remain confident in the ability of Reblozyl to improve outcomes for patients with myelofibrosis-associated anemia and believe the totality of these results, including meaningful improvements in transfusion burden and hemoglobin levels, support the potential to address an unmet need in patients who have few treatment options,” remarked Bristol Myers Squibb senior vice president and head of Development, Hematology, Oncology, and Cell Therapy Anne Kerber.

INDEPENDENCE is a phase 3, double-blind, randomized trial of luspatercept for patients with myeloproliferative neoplasm-associated myelofibrosis, who were also receiving JAK2 inhibitor therapy and required RBC transfusions. The investigators compared the treatment with placebo, and the trial’s primary end point was the proportion of patients who achieved RBC transfusion independence during any consecutive 12-week period within the first 24 weeks of treatment. The study agent did not meet this end point as compared with placebo (P=0.0674).

In terms of the secondary end points of the trial, the study agent had performance success, which the company said was consistent with prior phase 2 trial results. An increased proportion of patients attained a 50% or better reduction in their RBC transfusion burden, and a greater number of patients experienced a hemoglobin level increase of 1 g/dL or more while experiencing transfusion independence for at least 12 consecutive weeks. Treatment-emergent adverse events that occurred during the trial were also consistent with the established safety profile for the agent, according to the company.

The current clinical indications for luspatercept-aamt in the US pertain to treating anemia in adults with transfusion-dependent beta-thalassemia, very low-risk to intermediate-risk myelodysplastic syndromes with ring sideroblasts, or myelodysplastic or myeloproliferative neoplasms with ring sideroblasts and thrombocytosis.

Bristol Myers Squibb views the INDEPENDENCE trial results as showing promise for luspatercept-aamt. In the wake of this trial, the company expects to engage in discussions with both the FDA and the European Medicines Agency (EMA) regarding submission of marketing applications for the agent.