Pyruvate kinase deficiency (PKD) is a deficiency of enzyme pyruvate kinase that leads to an easy breakdown of red blood cells, resulting in hemolytic anemia. Mitapivat is an oral small-molecule allosteric activator of pyruvate kinase in RBC, but its safety and efficacy are unknown. The objective of this study is to evaluate the effectiveness and safety of mitapivat in PKD.

This is an uncontrolled, phase-2 clinical study that includes a total of 52 adults with pyruvate kinase deficiency who were not receiving red-cell transfusions. The participants were randomly assigned to 50 mg or 300 mg mitapivat twice daily for 24-weeks. The primary outcomes were the increase in pyruvate kinase levels and adverse effects.

A total of 26 patients (50%) reported an increase in more than 1.0 g per dL in the hemoglobin level. The mean maximum increase was 3.4 mg per dL, and 77% of the patients had an increase of more than 1.0 mg per dL in the HG level. Common adverse events included headache and insomnia. Some serious adverse events, like small-molecule allosteric activator of pyruvate kinase, occurred in 4% of the participants. 

The research concluded that mitapivat was associated with a rapid increase in hemoglobin levels in 50% of adults with PKD, and the adverse events for transient and low-grade.