Hemoglobinopathies

At the 63rd Annual Meeting of the American Society of Hematology (ASH), researchers from the Sickle Cell Branch of the National Heart, Lung, and Blood Institute and the National Institute of Diabetes and Digestive and Kidney Diseases presented results of a small study (abstract 10) of the oral antisickling agent mitapivat (AG-348). Study authors also included researchers from Agios Pharmaceuticals, Inc. Mitapivat increases glycolytic activity, which in turn reduces intracellular levels of 2,3-diphosphoglycerate (2,3-DPG), thereby decreasing the hemoglobin S (HbS) polymerization that causes sickling. ATP level increases that occur in parallel with this process improve the integrity of red blood cell (RBC) membranes. At ASH, the investigators reported that, in 16 evaluable patients (11 male; mean age, 39 years) with confirmed sickle cell disease (HbSS) treated with either 3 or 4 ascending dose levels of mitapivat (5, 20, 50, 100 mg twice daily) for 2 weeks) followed by a 12-15 day drug taper, this agent improved anemia, reduced markers of hemolysis, decreased levels of 2,3-DPG and increased levels of ATP, improved oxygen affinity, and decreased the sickling rate, "signaling its potential to improve clinically meaningful outcomes in SCD," the authors reported. An ongoing extension study (ClinicalTrials.gov Identifier: NCT04610866) will evaluate long-term effects of mitapivat in SCD.