Developer seeking FDA’s accelerated approval for mitapivat for SCD
Therapy shown in trial to boost levels of oxygen-carrying protein in blood cells
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Agios Pharmaceuticals has filed an application with the U.S. Food and Drug Administration (FDA) seeking accelerated approval of mitapivat, its oral therapy for sickle cell disease (SCD).
The developer said it expects to receive notice of acceptance of the application and the anticipated review timeline following the FDA’s 60-day filing review period.
“The submission of the mitapivat [application] represents an important milestone for the sickle cell community, which urgently needs new treatments that can address key underlying aspects of this debilitating and deadly disease,” Sarah Gheuens, MD, PhD, Agios’ chief medical officer and head of research and development, said in a company press release. “We look forward to continued engagement with the FDA throughout the review process.”
The application includes data from the global Phase 2/3 RISE UP clinical trial (NCT05031780), demonstrating that mitapivat — which works by activating a protein called pyruvate kinase, or PK — significantly boosted hemoglobin levels, the oxygen-carrying protein in red blood cells, in people with SCD.
“We believe mitapivat is well-positioned to become the first PK activator approved in the U.S. for sickle cell disease,” Gheuens said.
Agios’ filing follows an agreement with the FDA to launch a separate confirmatory trial, a requirement of the accelerated approval pathway. This pathway permits marketing authorization based on preliminary safety and effectiveness data from clinical trials.
Full FDA approval would still depend on confirmatory trial results
Full FDA approval of the drug would be contingent on the results of the confirmatory trial, which will be designed to demonstrate a clinically meaningful reduction in the blood transfusion burden for SCD patients. The trial is expected to enroll more than 150 SCD patients, ages 12 and older.
In SCD, a rare inherited disorder, abnormal hemoglobin causes red blood cells to become rigid and sickle-shaped. This leads to premature red blood cell destruction, known as hemolysis, and blood vessel blockages that trigger painful vaso-occlusive crises.
Mitapivat is designed to activate PK, a protein that boosts red blood cell energy production. It also reduces 2,3-DPG, a molecule elevated in SCD that promotes abnormal red blood cell sickling.
The oral therapy is already approved in the U.S. as Pyrukynd for adults with pyruvate kinase deficiency and Aqvesme for thalassemia, another bleeding condition.
Mitapivat holds orphan drug designation for SCD in both the U.S. and the European Union. This status offers certain incentives, including fee exemptions and market exclusivity should a treatment ultimately be approved, to encourage the development of rare-disease drugs.
Mitapivat shown to increase hemoglobin levels in SCD patients
RISE UP enrolled 286 SCD adolescents and adults with low hemoglobin levels who had experienced two to 10 pain crises in the previous year. In the study’s Phase 2 portion, twice-daily mitapivat was shown to outperform a placebo in boosting hemoglobin levels and reducing the frequency of pain crises.
The Phase 3 portion also met its main goal of showing that twice-daily mitapivat led to higher rates of hemoglobin response — an increase of at least 1.0 g/dL between six months and one year of treatment — than the placebo after one year. The annualized rate of pain crises was also reduced (2.62 vs. 3.05), but the difference was not statistically significant, suggesting it could have occurred by chance.
Still, participants who achieved the hemoglobin response also experienced clinically meaningful reductions in pain crises, fatigue, and hospitalizations.
“Mitapivat significantly improved hemoglobin concentration and reduced hemolysis in patients with sickle cell disease, translating into clinically meaningful benefits in pain crises and related hospitalizations, as well as fatigue, for those who achieved a hemoglobin response,” Gheuens said.
Mitapivat’s safety profile was consistent with prior studies. Participants completing RISE UP’s Phase 2 or 3 portions could enter the trial’s open-label extension phase, in which all are receiving the therapy for up to four years.
Mitapivat significantly improved hemoglobin concentration … in [some] patients with sickle cell disease, translating into clinically meaningful benefits in pain crises and related hospitalizations.
New RISE UP data on mitapivat, showing reductions in the blood transfusion burden and changes in patient-reported outcomes, will be presented in an oral plenary session at the 31st European Hematology Association Congress (EHA 2026), to be held June 11-14 in Sweden.
In a separate company press release, Gheuns said this EHA session “is an important opportunity to present new data showcasing the strong anti-hemolytic profile of mitapivat and its potential to address the urgent need for novel therapeutic options in sickle cell disease.”
Altogether, the “presentations at EHA 2026 build on over a decade of clinical and preclinical research that has consistently demonstrated the transformative potential of mitapivat as a disease-modifying oral medicine for hemolytic anemias,” Gheuens added.
