Key Takeaways
- Reblozyl misses primary endpoint in Phase III trial: The INDEPENDENCE study did not meet its primary goal of achieving transfusion independence in patients with myelofibrosis-associated anemia.
- Secondary endpoints show clinical benefit: Patients receiving Reblozyl experienced meaningful improvements in transfusion burden and hemoglobin levels, supporting continued evaluation.
- Safety profile remains consistent: Adverse events were in line with previous data, reinforcing Reblozyl’s established safety across approved indications.
Results from the Phase III INDEPENDENCE trial (NCT04717414) showed that Bristol Myers Squibb’s (BMS) Reblozyl (luspatercept-aamt), in combination with Janus kinase (JAK) inhibitor therapy, failed to meet its primary endpoint in treating anemia in adult patients with myelofibrosis (MF) who require red blood cell (RBC) transfusions. However, the company noted that patients receiving Reblozyl experienced numerically and clinically meaningful improvements in transfusion independence, consistent with earlier Phase II findings.1
Did Reblozyl Show Enough Benefit to Advance in Myelofibrosis-Associated Anemia?
“It is promising to see that Reblozyl led to clinically relevant improvement of anemia for patients with myelofibrosis, where patients often become increasingly transfusion dependent over time,” said Anne Kerber, SVP, head of development, hematology, oncology, cell therapy, BMS, in a press release. “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.”
Study Design and Endpoints
- The double-blind, randomized INDEPENDENCE trial compared the efficacy and safety of Reblozyl to placebo in 313 patients with myeloproliferative neoplasm-associated MF on JAK2 inhibitor therapy who required RBC transfusions.
- The primary endpoint of the trial was the proportion of patients who became RBC-transfusion-free over any consecutive 12-week period starting within the first 24 weeks, while the key secondary endpoint was the proportion of patients who became RBC transfusion independent over any consecutive 16-week period, starting within the first 24 weeks.
- Other secondary endpoints included increase in hemoglobin levels and at least a 50% reduction in RBC transfusion burden.1,2
Key Findings and Safety Results
- While exact numbers weren’t revealed, secondary endpoints showed that patients treated with Reblozyl achieved significant reductions in transfusion burden and increases in hemoglobin levels while remaining transfusion independent.
- Serious adverse events (AEs) occurred in approximately 3.6% of patients, which included cerebrovascular accident and deep vein thrombosis.
- Common all-grade AEs included headache, bone pain, arthralgia, fatigue, cough, abdominal pain, diarrhea, and dizziness.
- The most common AEs included fatigue, musculoskeletal pain, dizziness, diarrhea, nausea, hypersensitivity reactions, hypertension, headache, upper respiratory tract infection, bronchitis, and urinary tract infection.
- Treatment-related AEs were reported to be consistent with the known safety profile of Reblozyl across all other indications.1
Disease Background and Incidence
According to the National Organization for Rare Disorders, the incidence rate of MF is estimated to be approximately 1.5 cases per 100,000 people in the United States. The global prevalence is currently unknown. Males and females are affected in equal numbers. While it can occur at any age, it is most common in people aged 50 years or older. The median age of diagnosis is 65 years. In children with MF, the disease most commonly manifests before a child reaches three years of age, and it is twice as common in girls than boys.3
Expert Perspective on Treatment Landscape
“Anemia remains a significant challenge in the treatment of myelofibrosis, with many patients still dependent on red blood cell transfusions or suboptimal treatment approaches that can sometimes worsen anemia associated with the disease,” said John Mascarenhas, MD, professor of medicine, Icahn School of Medicine at Mount Sinai, director, center of excellence for blood cancers and myeloid disorders, Tisch Cancer Institute, in the press release. “Patients with myelofibrosis and anemia are difficult to treat, and these results show that Reblozyl can have an important impact on anemia associated with the disease.”
References
- Bristol Myers Squibb Announces Topline Results from Phase 3 INDEPENDENCE Trial for Reblozyl® (luspatercept-aamt) in Adult Patients with Myelofibrosis-Associated Anemia. BMS. July 18, 2025. Accessed July 18, 2025. https://news.bms.com/news/corporate-financial/2025/Bristol-Myers-Squibb-Announces-Topline-Results-from-Phase-3-INDEPENDENCE-Trial-for-Reblozyl-luspatercept-aamt-in-Adult-Patients-with-Myelofibrosis-Associated-Anemia/default.aspx
- An Efficacy and Safety Study of Luspatercept (ACE-536) Versus Placebo in Subjects With Myeloproliferative Neoplasm-Associated Myelofibrosis on Concomitant JAK2 Inhibitor Therapy and Who Require Red Blood Cell Transfusions (INDEPENDENCE). Clinicaltrials.gov. Accessed July 18, 2025. https://clinicaltrials.gov/study/NCT04717414
- Primary Myelofibrosis. NORD. Accessed July 18, 2025. https://rarediseases.org/rare-diseases/primary-myelofibrosis/#affected
