February 1, 2027, Set as New FDA Decision Date for Mitapivat in Sickle Cell Disease
Key Facts
Agios set February 1, 2027, as the new target date for the U.S. Food and Drug Administration’s decision on its supplemental application for mitapivat to treat sickle cell disease. The new date replaces the previous target date of November 1, 2026, according to the company. Agios said the agency requested additional information to assess whether the drug needs a risk evaluation and mitigation strategy. The company added that it is continuing label discussions with the agency, including potential elements of such a strategy. Agios said it is ready to launch the drug, while the new date extends the wait for a regulatory decision.
The FDA had granted the application priority review under the accelerated approval pathway and set November 1, 2026, as the target decision date. Agios said priority review is intended to reduce the review period from 10 months under the standard pathway to 6 months. The request for additional information comes at a stage of the application review that may include consideration of safety and labeling requirements before a decision. The company said the regulatory question concerns whether a risk evaluation and mitigation strategy is needed, without that alone determining the outcome of the review. Mitapivat is an oral pyruvate kinase activator, according to Agios.
The application was based on data from the two global, randomized, double-blind, placebo-controlled RISE UP trials, which included patients aged 16 years and older. The trial enrolled 207 participants, randomized in a 2-to-1 ratio between mitapivat and placebo; 138 received the drug and 69 received placebo. In the Phase 3 results, Agios reported a hemoglobin response in 40.6% of participants in the mitapivat group, compared with 2.9% in the placebo group. The company said the difference was statistically significant, with a p-value of less than 0.0001. These results provide part of the clinical basis for the application, while approval remains subject to the agency’s decision on the regulatory filing.
In other trial analyses, Agios said the proportion of patients who required transfusions was 23.9% with mitapivat, compared with 40.6% with placebo, a relative reduction of 41.1%. The mean number of red blood cell units transfused per patient was also 0.70 with the drug and 1.59 with placebo, which the company described as a relative reduction of 55.9%. These results relate to transfusion burden, which the confirmatory program is designed to assess. The Phase 3 RAINIER trial is required under the accelerated approval pathway to verify clinical benefit. The FDA says the pathway allows early approval based on a surrogate endpoint, while requiring companies to conduct studies confirming the expected clinical benefit.
Agios said the confirmatory RAINIER trial was designed to assess reductions in transfusion burden among patients aged 12 years and older. It is planned to enroll approximately 159 participants in a 52-week randomized, double-blind, placebo-controlled period. The primary endpoint measures the proportion of patients who achieve transfusion-free status during the period from week 4 through week 52. Alongside the U.S. pathway, the company said it submitted an application in the second quarter of 2026 for regulatory approval to treat sickle cell disease in Saudi Arabia. These steps place the confirmatory trial and the Saudi application among the next milestones for the mitapivat program, while the U.S. application awaits the new target date of February 1, 2027.