Mitapivat (AG-348) - (RISE UP)

July 7, 2026: Agios Pharmaceuticals, Inc. (NASDAQ: AGIO) announced the FDA has accepted its supplemental NDA (sNDA) for mitapivat, an oral pyruvate kinase (PK) activator, for sickle cell disease, granting Priority Review. The filing is submitted under the accelerated approval pathway, with a PDUFA goal date of November 1, 2026.

The sNDA is supported by the global RISE UP Phase 2 and Phase 3 program in patients aged ≥16 years with sickle cell disease. The RISE UP Phase 3 trial (NCT05031780) was a 52-week, randomized, double-blind, placebo-controlled study (n=207; 2:1 mitapivat 100 mg BID vs placebo) followed by an open-label extension; primary endpoints included hemoglobin response (≥1.0 g/dL increase from baseline in average hemoglobin from Week 24–52) and annualized rate of sickle cell pain crises, with multiple hematologic and PRO secondary endpoints.

Agios also described REIGNITE, the required Phase 3 confirmatory trial (NCT07656415) for accelerated approval, designed to assess transfusion-burden reduction in sickle cell disease patients aged ≥12 years (n≈159; 2:1 randomization; primary endpoint transfusion-free status Week 4–52).