The United States Food and Drug Administration has extended its review of Agios Pharmaceuticals mitapivat for sickle cell disease to 1 February 2027. The new Prescription Drug User Fee Act goal date replaces the original target of 1 November 2026, a delay of three months. Agios announced the extension on 30 October 2026. The application is a supplemental New Drug Application for the drug, an oral pyruvate kinase activator, and it was submitted under the accelerated approval pathway with Priority Review.
The extension followed a request for additional information about whether a Risk Evaluation and Mitigation Strategy, known as a REMS, is necessary for the drug in sickle cell disease. The agency made that request on 9 October 2026, three weeks before the original goal date. Agios submitted its response on 19 October 2026. On 28 October 2026, the agency told the company that the response had been classified as a major amendment to the application. That classification added three months to the review period.
Why the Mitapivat review was extended
The company response included about nine months of updated safety data through 9 October 2026, drawn from the ongoing open label extension periods of the RISE UP Phase 2 and Phase 3 trials. The company reported no cases of hepatocellular injury among patients with sickle cell disease treated with mitapivat that show a pattern and severity similar to those seen in the thalassemia trials. Agios stated that the benefit risk profile of the drug in sickle cell disease remains unchanged.
The REMS question traces back to the thalassemia programme. In the thalassemia trials, five of 301 patients treated with the drug across the double blind and open label periods experienced liver injury reactions, and two of these were serious. A REMS is a safety programme that can include monitoring or other conditions beyond the standard label, and labelling discussions, including potential REMS elements, are ongoing.
Agios chief executive Brian Goff said the company has strong conviction in the potential of the drug for people living with sickle cell disease, based on the RISE UP programme and the additional data submitted in response to the agency request. He said the Priority Review reflected the serious need in the disease, and that the urgency has not changed. The company said it remains launch ready while the extended review runs.
What the Mitapivat RISE UP trial showed
The application builds on the global, double blind, placebo controlled RISE UP Phase 3 trial. The trial randomised 207 patients aged 16 years and older in a ratio of two to one to mitapivat at 100 mg twice daily, with 138 patients, or placebo, with 69 patients, for 52 weeks. Its dual primary endpoints were haemoglobin response and the annualised rate of sickle cell pain crises.
Detailed results presented at the European Hematology Association 2026 Congress showed that 40.6 percent, or 56 of 138 patients receiving mitapivat, achieved a haemoglobin response, compared with 2.9 percent, or two of 69 patients, on placebo. From week 24 to week 52, mitapivat improved haemoglobin, with a least squares mean change of 0.769 g/dL against 0.026 g/dL for placebo, and indirect bilirubin, with a change of minus 16.03 micromol per litre against 0.88 micromol per litre.
The annualised rate of sickle cell pain crises was lower with mitapivat, at 2.62 against 3.05 for placebo, but the difference did not reach statistical significance. Fatigue scores showed no overall difference between the arms. New analyses reported a 41.1 percent relative reduction in the proportion requiring transfusion, and a 55.9 percent relative reduction in average red blood cell units transfused per patient. Rates of treatment emergent adverse events were similar, and no treatment related deaths occurred.
Mitapivat status and the February date
Mitapivat is already sold as Pyrukynd, and it is approved in the United States for adults with pyruvate kinase deficiency and for thalassemia. The sickle cell application would expand its use to a further group of patients. Market reports put the United States sickle cell population at roughly 100,000 people.
The new goal date of 1 February 2027 is a target action date, not a guarantee of approval on that day. The agency can still ask further questions, and the labelling discussions, including any REMS elements, remain open. For patients and clinicians, the practical effect is a longer wait for a decision on whether the drug becomes available for sickle cell disease. Agios said it will report further results in its third quarter earnings report, scheduled for 5 November 2026.