Aqvesme (Mitapivat), First Oral Option for Anemia in Thalassemia, Cleared by FDA

The FDA has approved Aqvesme (mitapivat), developed by Agios Pharmaceuticals, an oral pyruvate kinase activator, to treat anemia in adults with alpha- or beta-thalassemia. This is the first oral treatment option for beta-thalassemia and the first drug approval for alpha-thalassemia.

The decision covers both non-transfusion-dependent and transfusion-dependent disease, and Aqvesme is expected to become available in the US in late January 2026 following implementation of a Risk Evaluation and Mitigation Strategy (REMS) program.

Thalassemia is a genetic blood disorder in which mutations disrupt production of the alpha or beta globin chains of hemoglobin, leading to early breakdown of red blood cells. The condition can result in chronic anemia, fatigue and complications over time. Some adults require regular transfusions — often every two to five weeks — while others receive them intermittently, and ongoing monitoring remains a significant part of care.

Aqvesme is an oral small-molecule activator of pyruvate kinase, an enzyme that helps red blood cells generate energy; supporting this pathway is intended to improve red blood cell function and survival.

The FDA’s decision is supported by two multinational, randomized, double-blind, placebo-controlled Phase III trials: ENERGIZE in adults with non-transfusion-dependent thalassemia and ENERGIZE-T in adults with transfusion-dependent disease. Together, the trials enrolled 452 adults across multiple regions.

In ENERGIZE-T, 258 adults were randomized 2:1 to mitapivat 100 mg twice daily or placebo and evaluated over 48 weeks. The primary endpoint — a transfusion reduction response, defined as at least a 50% decrease in the number of red blood cell units transfused with a reduction of at least two units in any consecutive 12-week period compared with baseline, which was achieved by 30% of patients receiving Aqvesme and 13% receiving placebo.

In ENERGIZE, 194 adults with non-transfusion-dependent thalassemia were randomized 2:1 and assessed over 24 weeks. A hemoglobin response — defined as at least a 1 g/dL increase from baseline in mean hemoglobin concentration at Week 24 — occurred in 42% of patients receiving Aqvesme compared with 2% receiving placebo.

Fatigue was assessed using the patient-reported FACIT-Fatigue questionnaire (0–52 scale, higher scores indicating less fatigue). From a baseline of approximately 36, patients treated with Aqvesme had a mean increase of 4.9 points versus 1.5 points with placebo. Participants who completed the double-blind phases in both studies were able to transition into open-label extension phases.

Agios has set a US wholesale acquisition cost (WAC) of approximately $425,000 per year for Aqvesme in thalassemia.

Aqvesme is available only through a REMS program because some patients in the trials experienced hepatocellular injury, most often within the first six months of treatment. Across the double-blind and extension phases, five cases of hepatocellular injury were reported among patients treated with mitapivat, including two requiring hospitalization. The most common adverse reactions reported in the trials were headache and insomnia.

Outside the US, the European Medicines Agency (EMA) has issued a positive opinion recommending approval for adults with alpha- or beta-thalassemia, with a final decision expected in early 2026. The therapy has also received approval in Saudi Arabia, where launch activities are underway.

The company also reported that a Phase III trial of mitapivat in sickle cell disease is ongoing, with topline results expected in 2026.

Current treatment approaches for patients with transfusion-dependent beta-thalassemia include erythroid-targeted therapies such as luspatercept, which is approved to treat anemia in adults who require regular red blood cell transfusions.

Treatments also include hematopoietic stem cell transplantation and gene-edited cell therapies such as Casgevy (exagamglogene autotemcel) for eligible patients ages 12 years and older. In December 2025, Vertex reported new data from ongoing Phase III studies of Casgevy in children ages five to 11 years, noting that efficacy and safety findings were generally consistent with results previously reported in patients ages 12 years and older and that the company plans to pursue global regulatory submissions in 2026, while use in the five to 11-year group remains investigational.

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