FDA Alert

FDA Approves Mitapivat as First Oral Treatment for Anemia in Adults With Alpha- or Beta-Thalassemia

Edited by:
Ashton L. Stahl

Key Highlights:

  • Mitapivat is the first FDA-approved oral therapy for anemia in adults with beta-thalassemia and the first approved drug for alpha-thalassemia.
  • Approval was supported by 2 multinational, randomized, double-blind, placebo-controlled trials.
  • Treatment was associated with reduced transfusion burden or improved hemoglobin levels, depending on transfusion status.
  • Mitapivat is available only through a risk evaluation and mitigation strategy program due to observed liver toxicity.

Last week, the FDA approved mitapivat tablets for the treatment of anemia in adults with alpha- or beta-thalassemia, an inherited blood disorder characterized by impaired hemoglobin production and chronic anemia. According to the FDA’s Center for Drug Evaluation and Research, the approval marks the first oral treatment option for adults with beta-thalassemia and the first drug approved for alpha-thalassemia. The decision was based on efficacy and safety data from 2 global phase 3 clinical trials reviewed by the FDA.

The FDA evaluated mitapivat based on results from 2 multinational, randomized, double-blind, placebo-controlled studies: ENERGIZE-T and ENERGIZE. ENERGIZE-T enrolled adults with transfusion-dependent thalassemia, while ENERGIZE focused on adults with non–transfusion-dependent thalassemia. Participants were randomized to receive mitapivat or placebo, and prespecified efficacy endpoints were assessed over 24 to 48 weeks, depending on the study.

Study Findings

In the ENERGIZE-T trial, 258 adults with transfusion-dependent thalassemia were enrolled, with 171 receiving mitapivat and 87 receiving a placebo. The primary efficacy endpoint was a transfusion reduction response, defined as a greater than 50% reduction in red blood cell transfusions with a decrease of at least 2 units over any consecutive 12-week period through week 48. A higher proportion of patients treated with mitapivat achieved this response compared with the placebo (30% vs 13%).

The ENERGIZE trial included 194 adults with non-transfusion-dependent thalassemia who were treated for 24 weeks. Among these participants, 130 received mitapivat and 64 received a placebo. The primary endpoint was a hemoglobin response, defined as a ≥ 1 g/dL increase from baseline in mean hemoglobin concentration at week 24. A hemoglobin response occurred in 42% of patients receiving mitapivat compared with 2% in the placebo group.

Clinical Implications

According to the study authors, the findings suggest that mitapivat may reduce transfusion requirements in transfusion-dependent thalassemia and improve hemoglobin levels in non–transfusion-dependent disease. Improvements in fatigue-related symptoms, measured using the FACIT-Fatigue scale, were also observed among patients treated with mitapivat, reflecting patient-reported benefits associated with anemia improvement.

Expert Commentary

“A higher proportion of patients taking [mitapivat] achieved a transfusion reduction response (30%) compared with the placebo group (13%) …[and] a higher proportion of patients taking [mitapivat] achieved a hemoglobin response (42%) compared with the placebo group (2%),” the researchers concluded.