Mitapivat Superior to Placebo for Pyruvate Kinase Deficiency

Early, sustained, clinically significant hemoglobin response seen in 40 percent of patients receiving mitapivat versus none in the placebo group

red blood cells
Adobe Stock

FRIDAY, April 22, 2022 (HealthDay News) -- The oral, first-in-class activator of erythrocyte pyruvate kinase, mitapivat, increases hemoglobin levels among patients with pyruvate kinase deficiency, according to a study published in the April 14 issue of the New England Journal of Medicine.

Hanny Al-Samkari, M.D., from Massachusetts General Hospital in Boston, and colleagues conducted a global, phase 3, randomized trial to examine the efficacy and safety of mitapivat in adults with pyruvate kinase deficiency who were not receiving regular red-cell transfusions. Participants were randomly assigned to mitapivat or placebo for 24 weeks (40 in each group). A hemoglobin response that was sustained at two or more scheduled assessments at weeks 16, 20, and 24 was the primary end point.

The researchers found that 40 percent of patients in the mitapivat group and none in the placebo group had a hemoglobin response (adjusted difference, 39.3 percent). With respect to each secondary end point (average change from baseline in the hemoglobin level, markers of hemolysis and hematopoiesis, and the change from baseline at week 24 in two pyruvate kinase deficiency-specific patient-reported outcome measures), patients who received mitapivat had a greater response than those who received placebo. Nausea and headache were the most common adverse events. Grade 3 or higher adverse events occurred in 25 and 13 percent of those receiving mitapivat and placebo, respectively.

"This is a 'disease modifying' therapy because it targets the underlying problem to improve or eliminate anemia and potentially prevent or reverse many of the other complications associated with pyruvate kinase deficiency," Al-Samkari said in a statement.

Several authors disclosed financial ties to pharmaceutical companies, including Agios Pharmaceuticals, which manufactures mitapivat and funded the study.

Abstract/Full Text (subscription or payment may be required)

Physician's Briefing