Bone Marrow Failure Disorders

On February 17, the US Food and Drug Administration (FDA) approved mitapivat (Pyrukynd) for the treatment of hemolytic anemia in adults with pyruvate kinase deficiency (PKD), a rare inherited disorder (estimated frequency: 3-9 cases per 1 million people) that causes premature destruction of red blood cells and leads to anemia. FDA approval of mitapivat, a first-in-class PK activator, was based on efficacy results of 2 clinical studies. In the first (ACTIVATE; ClinicalTrials.gov Identifier: NCT03548220), which included 80 adults with PKD who did not receive regular blood transfusions, 40% of participants randomized to mitapivat (average treatment duration: 24 weeks) had a hemoglobin (Hb) response compared with no participants receiving placebo. (Response was defined as a 1.5 g/dL or greater increase in Hb concentration beginning from study initiation and sustained at 2 or more scheduled assessments.) In the second study (ACTIVATE-T; ClinicalTrials.gov Identifier: NCT03559699), a single-arm trial of mitapivat (average treatment duration: 40 weeks) in 27 adults with PKD who were regularly transfused, 33% of participants had a reduction in transfusion burden, including 22% who did not require any transfusions over the last 24 weeks of treatment. The most common side effects observed in these studies were decreased levels in men of estrone and estradiol (not evaluable in women due to normal fluctuations in hormone levels and use of hormonal contraception), increased levels of urate, back pain, and joint stiffness.