Mitapivat improves Hb, decreases hemolysis in pyruvate kinase deficiency: NEJM

USA: Mitapivat significantly increases the hemoglobin level, improves patient-reported outcomes, and decreases hemolysis in patients with pyruvate kinase deficiency, a recent study has found. The researchers identified no new safety signals in the patients who received mitapivat. The study appears in the New England Journal of Medicine. 

"The lifelong anemia associated with pyruvate kinase deficiency results in chronic fatigue, reduced exercise tolerance, and a reduced ability to concentrate at work or school, which can make it a challenge to get through even a normal day," says lead author Hanny Al-Samkari, MD, a hematologist and clinical investigator at MGH and an assistant professor of Medicine at Harvard Medical School. "Moreover, most patients develop other potentially serious complications, like iron overload in the liver and/or heart (which can cause cancer or death), osteoporosis, gallbladder disease, blood clots, and other issues."

Pyruvate kinase deficiency is a rare, hereditary, chronic condition that is tied to hemolytic anemia. In a phase 2 study, mitapivat, an oral, first-in-class activator of erythrocyte pyruvate kinase was shown to increase the hemoglobin level in patients with pyruvate kinase deficiency.

Hanny Al-Samkari and colleagues evaluated the safety and efficacy of mitapivat in adults with pyruvate kinase deficiency who were not receiving regular red-cell transfusions. They were assigned to receive either mitapivat (5 mg twice daily, with potential escalation to 20 or 50 mg twice daily) or a placebo for 24 weeks.