The FDA has delayed its decision on Agios Pharmaceuticals’ supplemental New Drug Application (sNDA) seeking approval of mitapivat for sickle cell disease (SCD). The agency extended the application’s Prescription Drug User Fee Act target action date from November 1, 2026, to February 1, 2027.
Agios said the extension followed what the FDA classified as a major amendment to the application. At the agency’s request, the company submitted additional information to help determine whether mitapivat would require a Risk Evaluation and Mitigation Strategy (REMS) for use in SCD.
On October 19, Agios provided approximately nine months of updated safety data collected through October 9 from the ongoing open-label extension periods of the Phase II/III RISE UP trial (NCT05031780). Data published in The Lancet showed a hemoglobin response in 56 of 138 patients receiving mitapivat, or 41%, compared with two of 69 patients receiving placebo, or 3%. The difference was statistically significant, with a two-sided p value below 0.0001.
The annualized rate of sickle cell pain crises was 2.6 with mitapivat and 3.1 with placebo, a difference that was not statistically significant. Serious adverse events occurred in 28 patients, or 20%, in the mitapivat group and 20 patients, or 29%, in the placebo group. One serious adverse event in the mitapivat group was considered treatment related.
Agios said the updated information continued to show no cases of hepatocellular injury among SCD patients treated with mitapivat that matched the pattern and severity observed in previous adult thalassemia trials. The company said its assessment of the treatment’s risk-benefit profile in SCD remained unchanged.
The delay affected Agios’ shares, which fell nearly 18% on Friday, from $37.23 to $30.55. J.P. Morgan analyst Tessa T. Romero said investors appeared focused on the possibility of a REMS and on how the FDA was assessing safety in the SCD population. She described the decision as a potential signal of a more cautious agency position.
Romero also noted that investors were concerned the delay could reduce mitapivat’s potential first-to-market advantage over Novo Nordisk’s SCD candidate etavopivat. Novo Nordisk has told investors it plans to advance that candidate to a first regulatory filing in the fourth quarter of this year.
Agios has marketed mitapivat for thalassemia under the name Aqvesme since January and for hemolytic anemia under the name Pyrukynd. The two products generated combined net product revenue of $65.491 million during the first half of this year, up 209% from $21.181 million in the same period of 2025.
Leerink Partners analyst Andrew Berens wrote that, even if a REMS is required, Agios expects no further delays and is prepared for a launch. He said the extension could postpone the commercial launch by about three months but did not believe it would change the commercial opportunity. In April, Berens estimated a 60% probability that mitapivat would reach the SCD market and projected peak U.S. sales of approximately $550 million.
Agios said it will continue discussions with the FDA on the product labeling, including possible REMS elements, while working to bring mitapivat to patients as soon as possible. The company plans to report its third-quarter results on Thursday.
The sNDA was submitted through the FDA’s accelerated approval pathway and received Priority Review. The pathway requires a confirmatory clinical trial, which Agios is addressing through the Phase III REIGNITE study (NCT07656415). The trial dosed its first patient in July and is designed to evaluate mitapivat’s effect on reducing transfusion burden in patients aged 12 and older with sickle cell disease.