FDA Grants Priority Review to Agios’ Mitapivat sNDA for Sickle Cell Disease

The US Food and Drug Administration (FDA) has accepted Agios Pharmaceuticals, Inc.’s supplemental New Drug Application (sNDA) for mitapivat in sickle cell disease (SCD) and granted the application Priority Review, along with assigning a Prescription Drug User Fee Act (PDUFA) goal date of November 1, 2026.

If approved, mitapivat would become the first oral pyruvate kinase (PK) activator for patients with sickle cell disease, providing a potential new treatment approach for a population with significant unmet medical needs.

Agios submitted the sNDA on May 12, 2026, under the FDA’s accelerated approval pathway, and was supported by results from the global RISE UP Phase 2 and Phase 3 clinical program.

“The Priority Review designation for the mitapivat sNDA marks an important milestone for the sickle cell community – a large, underserved population that has long needed new treatment options to help manage the significant burden of disease,” said Sarah Gheuens, MD, PhD., Chief Medical Officer and Head of R&D at Agios, in a statement.

Mitapivat and Sickle Cell Disease

Mitapivat is an oral pyruvate kinase (PK) activator designed to improve red blood cell energy metabolism. By increasing ATP production and lowering levels of 2,3-diphosphoglycerate (2,3-DPG), mitapivat is intended to improve red blood cell health and reduce processes associated with red blood cell sickling and hemolysis.

The therapy is already approved in the United States for adults with other rare hemolytic anemias, including pyruvate kinase deficiency and thalassemia.

RISE UP Phase 3 Trial Results

The global, randomized, double-blind, placebo-controlled RISE UP Phase 3 trial evaluated mitapivat in patients aged 16 years or older with sickle cell disease. The study enrolled 207 participants who were randomized 2:1 to receive oral mitapivat 100 mg twice daily (n=138) or matched placebo (n=69), followed by an open-label extension period.

The 52-week double-blind period met the primary endpoint of hemoglobin response, defined as a sustained increase in average hemoglobin concentration from baseline. The trial also met key secondary endpoints evaluating changes in hemoglobin concentration and indirect bilirubin, a marker of hemolysis.

Mitapivat also demonstrated a numerical reduction in the annualized rate of sickle cell pain crises compared with placebo, however, this difference did not achieve statistical significance.

Among participants completing the double-blind treatment period, 87.0% (120/138) of patients in the mitapivat group and 81.2% (56/69) of patients in the placebo group completed the 52-week period. Nearly all participants who completed the double-blind period entered the open-label extension.

Confirmatory Trial Under Accelerated Approval Pathway

As part of the accelerated approval pathway, Agios is conducting the REIGNITE Phase 3 confirmatory trial to further evaluate the clinical benefit of mitapivat in sickle cell disease.

The global REIGNITE trial is designed to assess whether mitapivat can reduce transfusion burden in patients aged ≥ 12 years with sickle cell disease. The study includes a randomized, double-blind, placebo-controlled period in which participants receive either mitapivat or placebo, followed by an open-label extension.

References

1. U.S. FDA grants priority review to Agios’ snda for Mitapivat in sickle cell disease – Agios Pharmaceuticals, Inc.. July 7, 2026. Accessed July 7, 2026. https://investor.agios.com/news-releases/news-release-details/us-fda-grants-priority-review-agios-snda-mitapivat-sickle-cell.

2. Safety and efficacy of Mitapivat in sickle cell disease (rise up): Results from the phase 2 portion of a global, double-blind, randomised, placebo-controlled trial - the Lancet haematology. Accessed July 7, 2026. https://www.thelancet.com/journals/lanhae/article/PIIS2352-3026(24)00319-3/abstract.