Mitapivat Shows Positive Haemoglobin Response in Phase III Sickle Cell Trial

Agios has reported topline results from the global RISE UP Phase III trial evaluating mitapivat, an oral pyruvate kinase activator, in patients aged 16 and above with sickle cell disease. The randomized, double-blind, placebo-controlled study enrolled 207 participants worldwide and assessed the drug’s effects on haemolysis and disease parameters over 52 weeks.

The trial met its primary endpoint, with mitapivat demonstrating a statistically significant haemoglobin response versus placebo. Key secondary endpoints, including indirect bilirubin and average haemoglobin concentration, also improved significantly. While annualized sickle cell pain crises (SCPCs) decreased, this did not reach statistical significance, and fatigue improvement was not met. Post hoc analyses showed haemoglobin responders experienced reduced fatigue, fewer SCPCs, and fewer hospitalizations.

The therapy was well tolerated, with adverse events comparable to placebo and no treatment-related deaths. Most participants continued into a 216-week open-label extension. Agios plans to pursue regulatory approval in the US.

26-11-2025