Cambridge, Massachusetts — October 30, 2026
Agios Pharmaceuticals, Inc. announced that the U.S. Food and Drug Administration (FDA) has established a new February 1, 2027 PDUFA goal date for the supplemental New Drug Application (sNDA) seeking approval of mitapivat for the treatment of sickle cell disease. The review extension follows the agency’s classification of Agios’ response to an additional information request as a major amendment, extending the review timeline by three months. The application was submitted under the FDA’s accelerated approval pathway and received Priority Review, with an original goal date of November 1, 2026. The FDA requested additional information on October 9 to assess whether a Risk Evaluation and Mitigation Strategy (REMS) would be necessary for mitapivat in this indication. Agios submitted its response on October 19, including approximately nine months of updated safety data from the ongoing open-label extension periods of the RISE UP Phase 2 and Phase 3 trials. The FDA notified the company of the major amendment classification on October 28. Agios said the benefit-risk profile of mitapivat in sickle cell disease remains unchanged and that it is continuing discussions with the agency on labeling and potential REMS requirements.
Updated Safety Data and FDA Review Extension
The additional information submitted by Agios included safety follow-up through October 9, 2026 from patients participating in the open-label extension periods of the RISE UP clinical program. According to the company, the updated data showed no cases of hepatocellular injury (HCI) among patients with sickle cell disease treated with mitapivat that displayed a pattern and severity similar to those observed in clinical trials involving adults with thalassemia. The FDA’s request focused on evaluating whether additional risk-management measures would be required before the medicine could be approved for sickle cell disease. The agency’s classification of the response as a major amendment triggered the three-month review extension. Agios said it will continue working with the FDA on labeling discussions, including potential REMS elements. The company also stated that it is launch-ready, citing its existing commercial infrastructure and established relationships with hematologists, sickle cell treatment centers and patients. CEO Brian Goff highlighted the significant unmet medical need in sickle cell disease, which affects approximately 100,000 people in the United States, and described the indication as a potential major growth driver for Agios. However, the new PDUFA date means that the FDA review remains ongoing; the announcement does not constitute an approval decision.
RISE UP Clinical Program and Confirmatory Study
The mitapivat sNDA is supported by the global, randomized, double-blind, placebo-controlled RISE UP Phase 2 and Phase 3 trials, which enrolled patients aged 16 years or older with sickle cell disease. In the Phase 3 study, 207 participants were randomized in a 2:1 ratio to receive oral mitapivat at 100 mg twice daily (138 participants) or matching placebo (69 participants) during a 52-week double-blind treatment period, followed by an open-label extension. The trial included two primary endpoints: hemoglobin response, defined as an increase of at least 1.0 g/dL from baseline in average hemoglobin between Weeks 24 and 52, and the annualized rate of sickle cell pain crises. Five key secondary endpoints assessed changes in hemoglobin concentration, indirect bilirubin, fatigue scores, hospitalization frequency for pain crises and reticulocyte levels. Of the 176 participants who completed the double-blind period, 174 entered the open-label extension. Separately, Agios dosed the first participant in July 2026 in REIGNITE, the Phase 3 confirmatory trial required under the accelerated approval pathway. The global study is designed to evaluate whether mitapivat reduces transfusion burden in patients with sickle cell disease aged 12 years or older. The confirmatory trial is intended to provide additional evidence of clinical benefit if accelerated approval is granted.
Advertisement
Mitapivat Mechanism and Agios Commercial Portfolio
Mitapivat is an oral pyruvate kinase (PK) activator designed to improve red blood cell energy metabolism by increasing adenosine triphosphate (ATP) levels and reducing 2,3-diphosphoglycerate (2,3-DPG). Its dual mechanism activates the PKR isoform in red blood cells and PKM2 in organ tissues, with the potential to address chronic hemolysis and pathways associated with long-term organ damage. Mitapivat is already marketed in the United States under two brand names for other hemolytic conditions: PYRUKYND, approved in 2022 for hemolytic anemia in adults with PK deficiency, and AQVESME, approved in 2025 for anemia in adults with alpha- or beta-thalassemia. AQVESME carries a boxed warning for serious hepatocellular injury and is distributed through a restricted REMS program. The FDA’s current assessment of whether a REMS is necessary for the sickle cell disease indication is therefore a key part of the ongoing regulatory review. Agios is headquartered in Cambridge, Massachusetts, and focuses on developing and commercializing medicines for rare diseases, with a foundation in hematology.
Source:Agios Pharmaceuticals, Press release
