MITAPIVAT significantly improved haemoglobin levels and markers of haemolysis in patients with sickle cell disease (SCD) in a Phase 3 trial, with additional clinical benefits observed among patients who achieved a haemoglobin response, a study presented at EHA 2026 congress found.
Mitapivat Targets Sickle Cell Anaemia
Persistent anaemia and ongoing haemolysis are major drivers of morbidity and mortality in SCD, contributing to acute complications, chronic organ damage and reduced quality of life. Mitapivat, an oral activator of pyruvate kinase in red blood cells, is designed to increase adenosine triphosphate (ATP) production while reducing levels of 2,3-diphosphoglycerate (2,3-DPG), potentially improving red blood cell health and reducing sickling. Investigators evaluated the efficacy and safety of the therapy in a global, randomised, double-blind, placebo-controlled Phase 3 trial involving 207 patients with SCD.
Mitapivat Trial Delivered Strong Haemoglobin Gains
Participants were randomised in a 2:1 ratio to receive mitapivat 100 mg twice daily (n=138) or placebo (n=69). The primary efficacy endpoint of haemoglobin response, defined as a rise of at least 1.0 g/dL from baseline between weeks 24 and 52, was achieved by 40.6% of patients receiving mitapivat compared with just 2.9% in the placebo group (p<0.0001). The treatment also produced significant improvements in average haemoglobin concentration, with a least-squares mean difference of 0.74 g/dL versus placebo, alongside marked reductions in indirect bilirubin, a key marker of haemolysis. However, the annualised rate of sickle cell pain crises did not differ significantly between treatment groups, at 2.62 events per year with mitapivat versus 3.05 with placebo.
Mitapivat Showed Safety and Clinical Benefits
Further analyses suggested that patients who achieved a haemoglobin response experienced broader clinical benefits. Responders had lower annualised rates of sickle cell pain crises and related hospitalisations than non-responders, alongside clinically meaningful improvements in fatigue scores. Safety outcomes were also favourable. Serious adverse events occurred in 20.3% of patients receiving mitapivat compared with 29.0% of those receiving placebo, while treatment discontinuation rates remained low in both groups. Only one serious adverse event in the mitapivat arm was considered treatment-related, and no new safety signals emerged during the study.
The findings indicate that mitapivat may offer a novel disease-modifying approach for SCD by addressing haemolytic anaemia through an oral mechanism of action. Longer-term studies will help clarify its impact on pain crises and other clinically meaningful outcomes.
Reference
Andemariam B et al. Efficacy and safety of mitapivat in sickle cell disease: results from the global, randomized, Phase 3 rise up trial. Abstract S102. EHA 2026 Congress, 10-14 June, 2026.
Featured Image; Sebastian Kaulitzki on Adobe Stock
- Author:
