Agios Pharmaceuticals (Nasdaq: AGIO) announced that the US FDA has granted Priority Review to its supplemental New Drug Application (sNDA) for mitapivat (Pyrukynd/Aqvesme), an oral pyruvate kinase (PK) activator, for the treatment of sickle cell disease (SCD). The Prescription Drug User Fee Act (PDUFA) goal date is November 1, 2026.
The sNDA was submitted under the FDA’s accelerated approval pathway, meaning a confirmatory trial is required to convert any initial approval to a traditional one. Priority Review shortens the target FDA review timeline from ten months to six months and is granted when a therapy may offer a significant improvement in safety or efficacy for a serious condition. The sNDA was filed following a pre-sNDA meeting in which the FDA recommended submission of a confirmatory trial proposal as a condition of pursuing accelerated approval.
The submission is based on data from the global, randomized, double-blind, placebo-controlled RISE UP Phase III trial in 207 patients aged 16 years and older with SCD, randomized 2:1 to mitapivat 100 mg twice daily or placebo for 52 weeks. As reported at the European Hematology Association 2026 congress, mitapivat demonstrated a statistically significant improvement in the primary endpoint of hemoglobin response — defined as a ≥1.0 g/dL increase from baseline in average hemoglobin from Week 24 through Week 52 — with 40.6% of patients in the mitapivat arm achieving this threshold versus 2.9% on placebo (2-sided p<0.0001). Among hemoglobin responders, mean hemoglobin concentration increased by 1.6 g/dL from baseline. The second co-primary endpoint, annualized rate of sickle cell pain crises, showed a numerical reduction with mitapivat but did not reach statistical significance. New analyses presented at EHA showed a 41.1% relative reduction in the proportion of patients requiring transfusions with mitapivat versus placebo (23.9% vs. 40.6%), and a 55.9% relative reduction in average red blood cell units transfused per patient (0.70 vs. 1.59 units). The safety profile was consistent with prior mitapivat trials, with no treatment-related deaths.
Mitapivat works by activating the pyruvate kinase R enzyme in red blood cells, increasing ATP production and lowering 2,3-diphosphoglycerate (2,3-DPG) levels. Elevated 2,3-DPG promotes the abnormal sickle conformation of hemoglobin, so reducing it decreases hemolysis and red cell sickling.