Agios shares fall 19% after mitapivat review extended to February 1, 2027
Key Facts
Agios Pharmaceuticals said the U.S. Food and Drug Administration moved the target date for a decision on its supplemental application for mitapivat to treat sickle cell disease to February 1, 2027, from November 1, 2026. The company said in a statement that the extension adds three months after the agency classified its response to an information request as a major amendment. In a Dow Jones report published at 11:21 a.m. Eastern time on October 30, the company’s shares fell 19% to $30.26. The stock closed at $37.23 on October 29, according to EL7 data. The regulatory decision delays the ruling on an application the company says is under priority review.
The regulatory process began on October 9, when the FDA requested additional information to assess whether the drug needs a Risk Evaluation and Mitigation Strategy. Agios submitted its response on October 19, then the agency informed the company on October 28 that the response had been classified as a major amendment, prompting the review extension. The company said its response included about nine months of updated safety data, through October 9, from ongoing open-label follow-up phases of the RISE UP Phase 2 and Phase 3 trials. The company linked the extended timeline to the classification of its response, while its announcement did not say the agency had excluded efficacy from its review.
On liver safety, Agios said cases of hepatocellular injury continue to occur among sickle cell disease patients treated with mitapivat, showing a pattern and severity similar to cases observed in trials of the drug in adults with thalassemia. The company added that the drug’s benefit-risk profile was unchanged. Published RISE UP results had said that liver abnormalities observed in the mitapivat and placebo groups did not suggest drug-induced hepatocellular injury. The safety data are part of the information the company submitted in response to the agency’s request, while the application review remains ongoing through the new target date.
In the Phase 3 RISE UP trial, the study included 207 participants aged 16 years or older, randomized 2 to 1 between mitapivat and placebo during a 52-week double-blind period. The annualized rate of pain crises was 2.62 with mitapivat and 3.05 with placebo, but the difference did not reach statistical significance, with a p-value of p=0.1213. The results reflect a divergence between the hemoglobin response endpoint and the pain-crisis measure, which did not show a statistically significant difference in the trial.
For indirect bilirubin, the change was minus 16.03 micromoles per liter in the drug group, compared with 0.88 micromoles per liter in the comparator group; the company said these changes were statistically significant. Mitapivat had previously received two approvals in the U.S. to treat hemolytic anemia in adults: pyruvate kinase deficiency in 2022, and thalassemia in 2025. The sickle cell application was submitted under the accelerated approval pathway and granted priority review.
Agios’s program includes the Phase 3 confirmatory REIGNITE trial, in which the company said it dosed its first participant in July 2026. The trial aims to measure mitapivat’s ability to reduce transfusion burden in sickle cell disease patients aged 12 years or older. Chief Executive Brian Goff said the company was launch-ready and would continue discussions with the FDA on the drug label, including potential elements of a Risk Evaluation and Mitigation Strategy. In a competing development program, Novo Nordisk expected to submit the first regulatory application for etavopivat in the fourth quarter of 2026. The next regulatory date for mitapivat remains February 1, 2027.