Agios’ Mitapivat Gains FDA Priority Review for Sickle Cell Disease

Agios Pharmaceuticals has reached a key regulatory milestone after the U.S. Food and Drug Administration (FDA) accepted the supplemental New Drug Application (sNDA) for mitapivat to treat sickle cell disease (SCD) and granted the application Priority Review. The FDA assigned a Prescription Drug User Fee Act (PDUFA) goal date of November 1, 2026. Submitted under the FDA’s accelerated approval pathway, the application positions mitapivat to become the first oral pyruvate kinase (PK) activator approved for sickle cell disease.

Mitapivat is already approved in the United States for adults with pyruvate kinase deficiency and thalassemia. The current application expands its potential use to patients aged 16 years or older with sickle cell disease, a rare inherited blood disorder marked by chronic hemolytic anemia, vaso-occlusive crises, progressive organ damage, and reduced life expectancy.

Oral PK Activation Targets Red Blood Cell Dysfunction

Mitapivat activates pyruvate kinase, a key enzyme in red blood cell energy metabolism. By increasing adenosine triphosphate (ATP) production and lowering 2,3-diphosphoglycerate (2,3-DPG) levels, the therapy improves red blood cell function and reduces hemoglobin sickling, helping limit hemolysis. Despite recent therapeutic advances, many patients continue to experience persistent anemia and recurrent painful crises, highlighting the need for additional disease-modifying treatment options.

 RISE UP Program Supported FDA Submission

The sNDA is supported by the global RISE UP clinical program, including the pivotal Phase 3 trial (NCT05031780).

The randomized, double-blind, placebo-controlled study enrolled 207 patients aged 16 years or older, who received oral mitapivat 100 mg twice daily or placebo during a 52-week treatment period before entering an open-label extension.

The trial evaluated two co-primary endpoints: the proportion of patients achieving at least a 1.0 g/dL increase in average hemoglobin from Weeks 24 through 52 and the annualized rate of sickle cell pain crises. Key secondary endpoints included changes in hemoglobin, indirect bilirubin, reticulocyte percentage, PROMIS Fatigue scores, and hospitalization rates related to pain crises. Of the 176 participants who completed the double-blind phase, 174 entered the open-label extension, providing additional long-term safety and efficacy data.

Extensive Clinical Experience Supports Review

Sarah Gheuens, MD, PhD, Chief Medical Officer and Head of Research & Development at Agios Pharmaceuticals, said the Priority Review marks an important step toward expanding treatment options for the underserved sickle cell disease community. She noted that the submission is supported by results from the RISE UP clinical program and more than 1,300 patient-years of clinical experience across hemolytic anemias, including pyruvate kinase deficiency, thalassemia, and sickle cell disease.

Priority Review shortens the FDA’s target review timeline from the standard 10 months to approximately six months for therapies that may provide meaningful improvements in treating serious diseases.

REIGNITE Confirmatory Trial Underway

As required under the accelerated approval pathway, Agios has initiated the REIGNITE Phase 3 confirmatory trial (NCT07656415).

The global study will enroll approximately 159 patients aged 12 years and older with sickle cell disease requiring regular transfusions. Participants are randomized in a 2:1 ratio to receive mitapivat 100 mg twice daily or placebo for 52 weeks. The primary endpoint is transfusion-free status between Weeks 4 and 52, while key secondary endpoints include transfusion burden, hemoglobin, indirect bilirubin, and lactate dehydrogenase (LDH). Successful completion of REIGNITE will be required to convert any accelerated FDA approval into traditional approval.

Reference

U.S. FDA Grants Priority Review to Agios’ sNDA for Mitapivat in Sickle Cell Disease – Agios Pharmaceuticals, Inc.