Agios Pharmaceuticals (NASDAQ:AGIO) saw its shares drop 12% after releasing Phase 3 RISE UP trial data for mitapivat in sickle cell disease, revealing a combination of encouraging and disappointing outcomes.
The study succeeded on its primary goal: 40.6% of patients treated with mitapivat achieved a hemoglobin increase of at least 1.0 g/dL, compared with just 2.9% of those given placebo. But the therapy fell short on a key clinical measure — reducing annualized sickle cell pain crises (SCPCs) — where results trended positively but did not reach statistical significance (2.62 vs. 3.05 for placebo).
Agios, headquartered in Cambridge, Massachusetts, noted that mitapivat delivered statistically meaningful improvements on two major secondary endpoints: hemoglobin change from baseline and reductions in indirect bilirubin, an indicator of hemolysis. However, the drug failed to hit the third secondary endpoint tied to patient-reported fatigue.
A post hoc analysis suggested that patients who achieved the hemoglobin response enjoyed broader clinical gains, including fewer pain crises, fewer hospitalizations, and better fatigue outcomes. Safety findings aligned with earlier studies, and investigators reported none of the liver-related issues previously seen in certain mitapivat trials.
“We plan to engage with the FDA to discuss these findings and our goal of bringing this innovative medicine to patients with sickle cell disease,” said Sarah Gheuens, Chief Medical Officer and Head of R&D at Agios.
Despite the uneven data, the company still intends to move forward. Agios plans to file a marketing application for mitapivat in sickle cell disease after its FDA meeting in the first quarter of 2026. It also reaffirmed expectations for a U.S. approval decision for PYRUKYND (mitapivat) in thalassemia by early December 2025.