Lancet
Efficacy and safety of mitapivat in patients with sickle cell disease (RISE UP): a phase 3, double-blind, global, randomised, placebo-controlled trial
By Andemariam B, Kuo KHM, Algahtani FH and 22 others.
Abstract
Background
Persistent haemolytic anaemia and recurrent vaso-occlusion drive complications and accelerate mortality in sickle cell disease. Mitapivat, an oral allosteric activator of pyruvate kinase, increases ATP and decreases 2,3-DPG with the potential to improve haemolytic anaemia and reduce sickling. We aimed to evaluate the efficacy and safety of mitapivat in patients with sickle cell disease.
Methods
We report results from RISE UP, a phase 3, double-blind, global, randomised, placebo-controlled trial from 69 sites across 15 countries. Patients older than 16 years with anaemia and recurrent sickle cell pain crises were randomly assigned (2:1) to either mitapivat 100 mg or placebo twice a day using permuted-block randomisation. Primary endpoints, assessed in all randomly assigned patients, were haemoglobin response (≥1·0 g/dL increase in average haemoglobin concentration from week 24 to week 52 compared with baseline) and annualised rate of sickle cell pain crises. This study is registered with ClinicalTrials.gov, NCT05031780, and the open-label extension is ongoing.