The U.S. Food and Drug Administration (FDA) has approved the drug mitapivat, marketed as AQVESME, for the treatment of anemia in adults suffering from non-transfusion-dependent alpha- and beta-thalassemia. This significant decision, announced by its manufacturer, Agios Pharmaceuticals, marks a pivotal development in addressing a condition that has historically seen limited treatment options.
Dr. Hanny Al-Samkari, who is the Peggy S. Blitz Endowed Chair in Hematology/Oncology at Massachusetts General Brigham Cancer Institute and an associate professor at Harvard Medical School, emphasized the importance of this approval. “Despite its severity, treatments for thalassemia have historically been limited, leaving some patients without any options,” he stated. “The results from the ENERGIZE and ENERGIZE-T Phase 3 trial demonstrate that AQVESME can help address anemia, fatigue, and the need for regular transfusions—key challenges of the disease.”
Mitapivat functions as a small-molecule oral activator of pyruvate kinase R (PKR), a crucial enzyme that supports the energy and longevity of red blood cells. By enhancing ATP production and reducing sickling in red blood cells, it holds promise for improving the quality of life for individuals with thalassemia.
Clinical Trial Findings
The FDA’s decision was primarily based on data from the phase 3 clinical trials known as ENERGIZE and ENERGIZE-T. The ENERGIZE trial was a double-blind, randomized, placebo-controlled study conducted across 70 hospitals in 18 countries. It enrolled 194 patients aged 18 years and older with non-transfusion-dependent alpha- and beta-thalassemia, all of whom had hemoglobin concentrations of ≤10 g/dL.
In the trial, participants were assigned in a 2:1 ratio to receive either mitapivat at a dosage of 100 mg twice daily or a placebo for a period of 24 weeks. Results revealed that 55 patients in the mitapivat group exhibited a hemoglobin response, compared to just one patient in the placebo group. This resulted in a statistically significant least-squares mean difference of 41% (95% CI, 32-50; P < 0.0001). While adverse events were reported more frequently in the mitapivat group (107 patients) compared to the placebo group (63 patients), these were primarily mild, including headache, insomnia, nausea, and upper respiratory infections. Importantly, no deaths occurred during the trial. The ENERGIZE-T trial focused on adults needing transfusions for their condition. Also a double-blind, randomized, placebo-controlled study, it included 258 participants who were assigned in a 2:1 ratio to receive mitapivat or a placebo for 48 weeks. The primary endpoint was a transfusion reduction response (TRR), defined as a ≥50% reduction in transfused red blood cell (RBC) units and a decrease of ≥2 units in any consecutive 12-week period compared to baseline. Results indicated that 30.4% of patients in the mitapivat arm achieved a TRR, in contrast to 12.6% in the placebo group. Additionally, significant reductions in transfusion burden were observed across several secondary endpoints, reinforcing the drug's efficacy: 13.5% in TRR2, 14.6% in TRR3, and 7.6% in TRR4 compared to minimal responses in the placebo group.
A Landmark Moment for Thalassemia Patients
Brian Goff, CEO of Agios, characterized the FDA’s approval as a landmark moment for the thalassemia community. “Today brings forward an innovative, disease-modifying oral medicine to address the urgent needs of people living with this devastating rare blood disorder,” Goff stated. With this approval, AQVESME stands out as the only medication indicated for treating anemia in both non-transfusion-dependent and transfusion-dependent alpha- and beta-thalassemia.
As patients and healthcare providers anticipate the availability of AQVESME, this breakthrough offers hope for improved management of thalassemia, a condition that has long posed challenges for those affected. The implications of this approval extend beyond clinical results, underscoring the importance of continued research and innovation in the treatment of rare blood disorders.
