Background:
Persistent anemia and hemolysis drive acute and chronic complications and contribute to increased mortality in sickle cell disease (SCD). Mitapivat, an oral activator of pyruvate kinase (PK), including the red blood cell–specific (PKR) and PKM2 isoforms, increases adenosine triphosphate (ATP) and decreases 2,3-diphosphoglycerate (2,3-DPG), with the potential to improve hemolytic anemia and reduce sickling.
Aims:
To evaluate the efficacy and safety of mitapivat vs placebo (PBO) in patients (pts) with SCD.
Methods:
In this global, double-blind, randomized, PBO-controlled, phase 3 trial, pts were randomized 2:1 to mitapivat 100 mg or PBO twice daily (NCT05031780). Primary endpoints were hemoglobin (Hb) response (≥1.0 g/dL increase in average Hb concentration from Week [Wk] 24 through Wk 52 compared with baseline) and annualized rate of sickle cell pain crises (SCPC). Key secondary endpoints included change in Hb concentration, markers of hemolysis, pt-reported fatigue (PROMIS Fatigue 13a T-scores), and frequency of hospitalizations for SCPC. Additionally, a post hoc analysis of pts who achieved Hb response was performed.