Bristol Myers Squibb's Reblozyl Fails Phase III Trial in Myelofibrosis-Associated Anemia, Company Remains Optimistic

Bristol Myers Squibb (BMS) announced that its anemia drug Reblozyl (luspatercept) failed to meet the primary endpoint in a late-stage clinical trial for patients with myelofibrosis-associated anemia. Despite this setback, the pharmaceutical giant remains encouraged by the drug's clinical activity and plans to discuss potential regulatory submissions with authorities.

INDEPENDENCE Trial Results and Implications

The Phase III INDEPENDENCE study evaluated Reblozyl in patients with myelofibrosis-associated anemia who required red blood cell transfusions and were on background treatment with a JAK inhibitor. The trial's primary endpoint was independence from red blood cell transfusions for 12 consecutive weeks starting in the first 24 weeks of treatment.

While the study did not achieve statistical significance for its primary endpoint, BMS reported that patients treated with Reblozyl showed a "numerical and clinically meaningful improvement" in transfusion independence. The P-value for the primary endpoint analysis was 0.0674, narrowly missing the typical 0.05 threshold for statistical significance.

Several secondary outcomes demonstrated clinically meaningful benefits favoring Reblozyl, including:

• Reduced transfusion burden
• Increased hemoglobin levels while remaining transfusion-independent
• Higher number of patients achieving at least a 50% reduction in transfusion burden

Anne Kerber, head of Hematology, Oncology, and Cell Therapy development at BMS, stated that 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."

Regulatory Strategy and Market Outlook

Despite the trial's failure to meet its primary endpoint, BMS plans to engage with the U.S. Food and Drug Administration (FDA) and the European Medicines Agency (EMA) to discuss potential marketing applications for Reblozyl in myelofibrosis-associated anemia.

Reblozyl, a recombinant fusion protein that improves the number and quality of mature red blood cells, is already approved for other indications:

1. Anemia in adult patients with beta thalassemia requiring regular transfusions (FDA approval in 2019)
2. Anemia in patients with very low- to intermediate-risk myelodysplastic syndromes or myeloproliferative neoplasms

The drug has been a strong performer for BMS, with sales reaching $1.77 billion in 2024, representing a 76% year-on-year increase. In the first quarter of 2025, Reblozyl generated $478 million in sales, a 35% growth compared to the same period last year.

BMS has projected that Reblozyl could reach peak sales of $4 billion or more. However, the recent trial setback may impact these projections, as it adds to a concerning trend of clinical failures for BMS this year.

BMS's Recent Clinical Setbacks

The Reblozyl trial failure is the latest in a series of disappointing results for BMS in 2025. All four pivotal life-cycle management trials for the company's existing drugs that have reported outcomes this year have turned up negative:

1. Opdualag (LAG-3/PD-1 combo) failed in adjuvant treatment for resected stage 3 or 4 melanoma
2. Camzyos showed no benefit in non-obstructive hypertrophic cardiomyopathy
3. Cobenfy stumbled as an adjunctive treatment for inadequately controlled schizophrenia
4. Reblozyl's failure in myelofibrosis-associated anemia

These setbacks are particularly concerning as these drugs were expected to help BMS navigate an upcoming patent cliff. The company had highlighted Reblozyl, along with four other products, as key to its growth portfolio, which was projected to exceed 50% of BMS's revenues in 2025.

Despite these challenges, BMS continues to pursue additional indications for Reblozyl. The phase 3 Element-MDS trial, testing the drug in nontransfusion-dependent myelodysplastic syndromes anemia, is expected to report results in 2027. Additionally, Reblozyl is being evaluated for use in alpha thalassemia.