The FDA has approved mitapivat (Aqvesme/Pyrukynd) as a treatment for anemia related to alpha- or beta-thalassemia in adults, being an oral pyruvate kinase (PK) activator [1]. Mitapivat acts as an allosteric PK activator, which increases PK activity, decreases 2,3-DPG and increases ATP in red blood cells, which may improve erythrocyte survival and hemoglobin values [6]. The approval is based on clinical trials in which treatment with mitapivat in the ENERGIZE trial in the non-transfused thalassemia group produced a hemoglobin response (defined as an increase in hemoglobin ≥1 g/dl) in 42.3% of patients versus 1.6% with placebo [1]. In the ENERGIZE-T trial in transfusion-dependent patients, more patients in the mitapivate group achieved a reduction in transfusion burden (defined as ≥50% reduction in transfusions and a reduction of at least 2 units in any consecutive 12-week period) - 30.4% vs 12.6% for placebo [1]. Previous approval of a mitapivate (Pyrukynd) was for hemolytic anemia in PK deficiency; for this indication, hemoglobin responses were observed in 40% of patients vs 0% for placebo in a randomized trial [4][6]. The most commonly reported adverse effects in early studies included insomnia, dizziness, and headache; in a phase 2 study in nontransfusion-dependent patients, the hemoglobin response rate was 80% (16/20) in the analysis group [2]. The FDA continued to review supplemental applications and the review process, including the allocation of appropriate fees under PDUFA [1].