Mitapivat versus Placebo for Pyruvate Kinase Deficiency

Pyruvate kinase deficiency is a rare, hereditary, chronic condition associated with hemolytic anaemia. In a phase 2 study, mitapivat, an oral, first-in-class activator of erythrocyte pyruvate kinase, increased the haemoglobin level in patients with pyruvate kinase deficiency. In this global, phase 3, randomized, placebo-controlled trial, we evaluated the efficacy and safety of mitapivat in adults with pyruvate kinase deficiency who were not receiving regular red-cell transfusions. Sixteen of the 40 patients (40%) in the mitapivat group had a haemoglobin response, as compared with none of the 40 patients in the placebo group (adjusted difference, 39.3 percentage points; 95% confidence interval, 24.1 to 54.6; two-sided P<0.001). In patients with pyruvate kinase deficiency, mitapivat significantly increased the haemoglobin level, decreased hemolysis, and improved patient-reported outcomes.