Mitapivat PDUFA Date for Sickle Cell Disease Extended to February 2027

Agios Pharmaceuticals announced the US Food and Drug Administration (FDA) has extended the Prescription Drug User Fee Act (PDUFA) goal date for mitapivat in sickle cell disease (SCD) by 3 months, moving the target action date from November 1, 2026, to February 1, 2027. The supplemental New Drug Application (sNDA) for the oral pyruvate kinase (PK) activator was submitted under the accelerated approval pathway and holds Priority Review.¹

According to Agios, the FDA classified the company’s response to a Risk Evaluation and Mitigation Strategy (REMS) information request as a major amendment, which triggered the extension.¹

“We have strong conviction in mitapivat’s potential to transform care for people living with sickle cell disease, grounded in the comprehensive data from the RISE UP clinical program and further supported by the additional data we submitted in response to the FDA’s recent request. The FDA granted this application Priority Review, underscoring the serious need in this disease, and that urgency has not changed,” , said in a statement. “Sickle cell disease affects approximately 100,000 people in the U.S. and is the largest indication we have pursued for mitapivat, and we expect it to be a significant growth driver for Agios. We are launch-ready, building on our commercial infrastructure and the strong relationships we have established over several years with hematologists, sickle cell centers, and patients. We will continue to work expeditiously with the goal of bringing mitapivat to patients with sickle cell disease as soon as possible.”

The delay comes nearly 4 months after the FDA granted Priority Review to the mitapivat sNDA in July 2026, following the company’s submission for accelerated approval earlier in the year. Mitapivat is already marketed as Pyrukynd for hemolytic anemia in adults with PK deficiency. It is also marketed as Aqvesme for anemia in adults with alpha- or beta-thalassemia, an indication carrying a boxed warning for hepatocellular injury and available only through a REMS.¹

Why Did the FDA Extend the Mitapivat PDUFA Date in Sickle Cell Disease?

On October 9, 2026, the FDA requested more information to help it decide whether mitapivat in SCD would require a REMS. On October 19, Agios responded with approximately 9 months of updated safety data, collected through October 9, from the open-label extension (OLE) periods of the phase 2 and phase 3 RISE UP trials. The agency classified the submission as a major amendment on October 28, which added a 3-month extension to the review.¹

The REMS question traces back to the thalassemia program. In the thalassemia trials, 5 of 301 patients treated with mitapivat across the double-blind and open-label periods experienced liver injury reactions, and 2 of these were serious.¹

Agios reported no cases of hepatocellular injury in mitapivat-treated patients with SCD resembling the pattern and severity seen in the adult thalassemia trials. The company stated the benefit-risk profile of mitapivat in SCD is unchanged.¹ Labeling discussions with the FDA, including potential REMS elements, are ongoing.¹

What Did The RISE UP Phase 3 Trial Show for Mitapivat in Sickle Cell Disease?

The application builds on findings from the phase 2 portion of RISE UP. The global, double-blind, placebo-controlled phase 3 trial randomized 207 patients aged 16 years and older in a 2:1 ratio to mitapivat 100 mg twice daily (n = 138) or placebo (n = 69) for 52 weeks. Its dual primary endpoints were hemoglobin response, defined as an increase of ≥ 1.0 g/dL from baseline in average hemoglobin from weeks 24 through 52, and annualized rate of sickle cell pain crises (SCPCs).¹

Detailed results presented at the European Hematology Association (EHA) 2026 Congress showed 40.6% (56/138) of patients receiving mitapivat achieved a hemoglobin response, compared with 2.9% (2/69) receiving placebo (P <.0001). From weeks 24 to 52, mitapivat also improved hemoglobin (least squares mean change, 0.769 vs 0.026 g/dL; P < .0001) and indirect bilirubin (−16.03 vs 0.88 µmol/L; P < .0001). The annualized SCPC rate was lower with mitapivat (2.62 vs 3.05), but the difference did not reach statistical significance, and fatigue scores showed no overall difference between arms.^2,3

New analyses showed a 41.1% relative reduction in the proportion of patients requiring transfusion (23.9% vs 40.6%). They also showed a 55.9% relative reduction in average red blood cell units transfused per patient (0.70 vs 1.59). Rates of treatment-emergent adverse events were similar between arms (97.1% vs 98.6%), and no treatment-related deaths occurred.²

Agios is conducting REIGNITE, the phase 3 confirmatory trial required under the accelerated approval pathway, to evaluate whether mitapivat reduces transfusion burden in patients with SCD aged 12 years and older. The first patient was dosed in July 2026, so the trial will be underway when the FDA makes its decision, as the pathway requires. Of the 176 patients who completed the RISE UP phase 3 double-blind period, 174 entered the OLE.¹

References

1. Agios Pharmaceuticals. Agios announces new PDUFA goal date of February 1, 2027, for mitapivat in sickle cell disease. Published October 30, 2026. Accessed October 30, 2026. https://investor.agios.com/news-releases/news-release-details/agios-announces-new-pdufa-goal-date-february-1-2027-mitapivat

2. Agios Pharmaceuticals. Agios showcases RISE UP phase 3 results at EHA 2026 plenary session reinforcing strong anti-hemolytic profile of mitapivat in sickle cell disease. Published June 13, 2026. Accessed October 30, 2026. https://agiospharmaceuticalsinc.gcs-web.com/node/19101

3. Andemariam B. Efficacy and safety of mitapivat in sickle cell disease: results from the global, randomized, phase 3 RISE UP trial. Presented at: European Hematology Association 2026 Congress; June 13, 2026; Stockholm, Sweden. Abstract S102.