FDA extends Agios’ mitapivat review to February 1, 2027, after classifying additional safety information for sickle cell disease as a major amendment.
Written By: Rishabh Sonawane, BPharm
Reviewed By: Pharmacally Editorial Team
Agios Pharmaceuticals has received a three-month extension to the FDA review of its supplemental New Drug Application (sNDA) for mitapivat in sickle cell disease (SCD). The extension follows the agency’s classification of the company’s response to an additional safety information request as a major amendment. The revised Prescription Drug User Fee Act (PDUFA) target action date is now February 1, 2027, moving beyond the original November 1, 2026 deadline.
FDA Requests Additional Safety Information for REMS Assessment
On October 9, 2026, the FDA requested additional information to determine whether mitapivat requires a Risk Evaluation and Mitigation Strategy (REMS) for its potential use in sickle cell disease. Agios submitted its response on October 19, providing approximately nine months of updated safety data through October 9 from the ongoing open-label extension (OLE) periods of the Phase 2 and Phase 3 RISE UP trials.
The updated analysis identified no cases of hepatocellular injury (HCI) in patients with sickle cell disease showing a pattern and severity comparable to those previously observed in clinical trials of mitapivat in adults with thalassemia.
On October 28, the FDA notified Agios that it classified the submission as a major amendment, triggering the standard three-month extension to allow the agency adequate time to evaluate the data and determine appropriate risk-management requirements. Agios stated that the findings do not alter its assessment of mitapivat’s positive benefit-risk profile in SCD, though the FDA’s decision regarding a REMS remains pending.
Clinical Background and Mechanism of Action
Mitapivat is an oral activator that targets the PKR isoform in red blood cells—elevating ATP levels and reducing 2,3-diphosphoglycerate (2,3-DPG) to increase oxygen affinity and prevent red blood cell sickling and hemolysis—while also activating PKM2 in organ tissues.
The sNDA is supported by data from the RISE UP Phase 2 and Phase 3 program. The pivotal Phase 3 study (NCT05031780) evaluated mitapivat (100 mg twice daily) against placebo in 207 patients aged 16 and older, measuring key endpoints including hemoglobin response and annualized rate of sickle cell pain crises (VOCs).
Confirmatory Trial and Regulatory Outlook
In July 2026, Agios initiated REIGNITE (NCT07656415), a confirmatory Phase 3 trial required under the accelerated approval pathway. REIGNITE evaluates whether mitapivat reduces transfusion burden in patients aged 12 years and older.
While the revised PDUFA date of February 1, 2027, extends the review window, Agios will continue ongoing labeling discussions with the FDA and advance commercial launch preparations. The key regulatory focal point moving forward remains whether the updated safety profile will allow approval without additional REMS requirements.
Reference
Agios Announces New PDUFA Goal Date of February 1, 2027, for Mitapivat Sickle Cell Disease sNDA; Company Is Launch-Ready and in Labeling Discussions with FDA, Agios, 30 October 2026
A Study Evaluating the Efficacy and Safety of Mitapivat (AG-348) in Participants with Sickle Cell Disease (RISE UP), ClinicalTrials.gov ID NCT05031780
About the Writer
Rishabha Sonawane, B.Pharm (LinkedIn) is healthcare writer with a strong interest in medical writing, regulatory affairs, clinical research, and AI-driven drug discovery. He has completed specialized training from the NIH and ICMR in clinical pharmacology, clinical research, and scientific writing. Passionate about evidence-based healthcare communication, he focuses on translating complex scientific research into clear, accurate, and engaging medical content.