The U.S. Food and Drug Administration (FDA) has officially approved mitapivat, marketed as AQVESME, for the treatment of anemia associated with both non-transfusion-dependent alpha-thalassemia and beta-thalassemia. This announcement, made by its parent company, Agios Pharmaceuticals, marks a significant advancement for patients facing this challenging blood disorder.
According to Hanny Al-Samkari, MD, the Peggy S. Blitz Endowed Chair in Hematology/Oncology at Massachusetts General Brigham Cancer Institute and an associate professor at Harvard Medical School, the approval addresses a longstanding gap in treatment options for thalassemia. “Despite its severity, treatments for thalassemia have historically been limited, leaving some patients without any options,” Al-Samkari noted. The results from the Phase 3 ENERGIZE and ENERGIZE-T trials underscore AQVESME’s potential to alleviate symptoms such as anemia and fatigue, as well as to reduce the necessity for regular blood transfusions.
Mitapivat acts as a small-molecule oral activator of pyruvate kinase R (PKR), an enzyme crucial for maintaining the health and longevity of red blood cells. By enhancing red blood cell survival, mitapivat addresses key issues linked to sickle cell disease, including increased adenosine triphosphate (ATP) levels and reduced sickling.
The FDA’s decision was supported by data from the Phase 3 trials. The ENERGIZE trial involved a double-blind, randomized, placebo-controlled design conducted across 70 hospitals in 18 countries. Participants were adults aged 18 and older with non-transfusion-dependent alpha- or beta-thalassemia and hemoglobin concentrations at or below 10 g/dL. In total, 194 patients were enrolled, with 130 receiving mitapivat and 64 given a placebo over a period of 24 weeks.
The primary endpoint focused on the change in hemoglobin response from baseline. The findings revealed that 55 patients in the mitapivat group achieved a hemoglobin response, compared to just one patient in the placebo group, resulting in a statistically significant difference (least-squares mean difference of 41%; 95% confidence interval of 32-50; P < 0.0001). Although adverse events were reported in 107 patients receiving mitapivat, the most common issues included headache, initial insomnia, nausea, and upper respiratory tract infection, with no deaths recorded. The follow-up ENERGIZE-T trial evaluated the efficacy and safety of mitapivat for adults with transfusion-dependent thalassemia. In this study, participants were also randomized in a 2:1 ratio to receive mitapivat or placebo over a 48-week period. The trial’s primary endpoint was the transfusion reduction response (TRR), defined as a reduction of at least 50% in transfused red blood cell units in any consecutive 12-week period compared to baseline.
In total, 258 patients were randomized, with 171 receiving mitapivat and 87 given a placebo. The results showed a TRR in 30.4% of patients in the mitapivat group versus 12.6% in the placebo group. Further, all key secondary endpoints demonstrated statistically significant reductions in transfusion burden, with reductions of 13.5% versus 2.3% for TRR2, 14.6% versus 1.1% for TRR3, and 7.6% versus 1.1% for TRR4.
In light of the approval, Brian Goff, CEO of Agios, stated, “Today is a landmark moment for the thalassemia community, bringing forward an innovative, disease-modifying oral medicine to address the urgent needs of people living with this devastating rare blood disorder.” With this decision, AQVESME becomes the first and only medication approved for treating anemia in both non-transfusion-dependent and transfusion-dependent alpha- and beta-thalassemia, offering hope to many patients and their families.
