Evaluating mitapivat for the treatment of alpha or beta thalassemia

Thalassemia is a group of diverse genetic disorders with worldwide distribution that affects hemoglobin synthesis. Until recently, the therapeutic approach to thalassemia was symptomatic, relying on red blood cell transfusions, treatment of comorbidities and of disease-related complications. However, novel therapeutic agents have recently been developed and are gradually being integrated into routine clinical practice.

One of the most promising agents is mitapivat (AG348), an oral pyruvate kinase activator that enhances the erythrocytic adenosine triphosphate (ATP) production. After series of preclinical and clinical studies, mitapivat has been suggested to be a safe and effective disease modifier for thalassemia. Large double blind randomized clinical trials have indicated that mitapivat may increase baseline hemoglobin levels, reduce transfusion burden, control ineffective erythropoiesis and hemolysis and improve quality of life.

Mitapivat presents as a potential game-changer in the management of patients with both α- and β-thalassemia, regardless of transfusion dependency. However, further post-marketing evidence is required in order to evaluate mitapivat profile under real‑world conditions and routine clinical practice.