The Food and Drug Administration (FDA) has accepted for Priority Review the New Drug Application (NDA) for mitapivat for the treatment of adults with pyruvate kinase deficiency.

Pyruvate kinase (PK) deficiency is a rare, inherited disease caused by mutations in the PKR gene resulting in a deficiency of the enzyme pyruvate kinase. The disease is characterized by an accelerated destruction of red blood cells. Mitapivat is a first-in-class, oral, selective small molecule allosteric activator of pyruvate kinase-R enzymes. 

The NDA submission is supported by data from 2 pivotal phase 3 studies, ACTIVATE ( Identifier: NCT03548220) and ACTIVATE-T ( Identifier: NCT03559699) that evaluated the efficacy and safety of mitapivat in adults with PK deficiency not regularly receiving blood transfusion and those regularly receiving transfusions, respectively. The ACTIVATE study included 80 patients who were randomly assigned 1:1 to receive either mitapivat or placebo; ACTIVATE-T included 27 patients who received mitapivat for 24 weeks.

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Results from ACTIVATE showed that mitapivat met the primary endpoint with 40% (n=16) of patients achieving a hemoglobin response compared with no patients in the placebo arm (2-sided P <.0001). Significant improvements in pre-specified key secondary endpoints were also observed, including markers of hemolysis and ineffective erythropoiesis, as well as patient-reported outcome measures.

Findings from ACTIVATE-T showed that 37% (n=10) of patients treated with mitapivat met the primary endpoint achieving a statistically significant and clinically meaningful transfusion reduction response, defined as at least a 33% reduction in transfusion burden, in the 24-week fixed dose period compared with historical transfusion burden (1-sided P =.0002). Moreover, there were 9 responders who achieved at least a 50% reduction in transfusion burden and 6 patients who were transfusion-free during the 24 weeks.

The safety profile for mitapivat in both studies was consistent with that seen in previous studies. The most common adverse reactions reported were nausea and headache.

A Prescription Drug User Fee Act (PDUFA) target date of February 17, 2022 has been set for the application.

“The acceptance of our NDA for mitapivat with Priority Review represents an important milestone on the path to expeditiously deliver the first potentially disease-modifying therapy for people with PK deficiency, a chronic, lifelong hemolytic anemia characterized by serious complications affecting multiple organs,” said Sarah Gheuens, MD, PhD, senior vice president of clinical development and incoming chief medical officer at Agios. 


  1. Agios announces FDA acceptance and Priority Review of New Drug Application for mitapivat for treatment of adults with pyruvate kinase deficiency. News release. Agios Pharmaceuticals, Inc. Accessed August 18, 2021.
  2. Agios announces updated data from ACTIVATE and ACTIVATE-T phase 3 studies of mitapivat in pyruvate kinase (PK) deficiency at the European Hematology Association Virtual Congress. News release. Agios Pharmaceuticals, Inc. June 11, 2021. Accessed August 18, 2021.

This article originally appeared on MPR