FDA Approves Pyrukynd for Hemolytic Anemia in Adults With Pyruvate Kinase Deficiency


The approval is based on the results of the ACTIVATE and ACTIVATE-T phase 3 studies, Agios Pharmaceuticals says.

The FDA has approved mitapivat (Pyrukynd, Agios Pharmaceuticals) for the treatment of hemolytic anemia in adults with pyruvate kinase (PK) deficiency, which is a lifelong and rare hemolytic anemia.

“The successful ACTIVATE and ACTIVATE-T studies demonstrate the impact of mitapivat in significantly improving hemolysis and anemia in PK deficiency,” Hanny Al-Samkari, MD, hematologist and clinical investigator at the Mass General Cancer Center and Harvard Medical School, said in a statement. “The FDA approval of mitapivat, a targeted agent and first disease-modifying medication in PK deficiency, is an encouraging step forward for these patients that addresses a significant unmet need.”

Agios is offering to eliminate the copay for mitapivat for eligible individuals who are commercially insured, as well as a patient assistance [program that offers free prescriptions to eligible individuals who are underinsured or uninsured.

Mitapivat is expected to be available in the United States about 2 weeks after approval. The FDA reviewed the drug under priority review, and mitapivat was previously granted orphan drug designation.

The FDA approval was based on results from 2 studies, ACTIVATE and ACTIVATE-T.

The studies included individuals with PK deficiency who were not regularly transfused (ACTIVATE) and regularly transfused (ACTIVATE-T).

The ACTIVATE trial achieved its primary endpoint, with mitapivat demonstrating a statistically significant increase in hemoglobin for individuals with PK deficiency who are not regularly transfused.

About 40% of individuals treated with mitapivat achieved a hemoglobin response where no individuals achieved this with the placebo.

Statistically significant improvements with mitapivat were shown for all pre-specified secondary endpoints, including markers of hemolysis and ineffective erythropoiesis compared with the placebo.

Individuals treated with mitapivat experienced jaundice, shortness of breath, and tiredness when assessed using the daily Pyruvate Kinase Deficiency Diary.

Serious adverse events (AEs) occurred in 10% of individuals, which included atrial fibrillation, gastroenteritis, musculoskeletal pain, and rib fracture.

The most common AEs included laboratory abnormalities for individuals with PK deficiency were arthralgia, back pain, and increased urate. Additionally, for males, this included decreased estradiol and estrone.

Furthermore, in the ACTIVATE-T trial, mitapivat also achieved its primary endpoint and demonstrated clinically meaningful and statistically significant reduction in the transfusion burden for individuals who were regularly transfused.

Approximately 33% of individuals achieved a transfusion reduction response, defined as an equal to or greater than 33% reduction in transfusion burden in the 24-week fixed-dose period. This was compared with the individual historical transfusion burden standardized to 24 weeks.

Additionally, approximately 22% of individuals were transfusion-free during the fixed-dose period, and the AEs reported in this study remained consistent with those observed in the ACTIVATE study.

An extension study for individuals with PK deficiency previously enrolled in either of the 2 phase 3 studies is ongoing and will evaluate the efficacy, long-term safety, and tolerability of mitapivat.


Agios announces FDA Approval of Pyrukynd (mitapivat) as first disease-modifying therapy for hemolytic anemia in adults with pyruvate kinase deficiency. Globe News Wire. News release. February 17, 2022. Accessed February 18, 2022. Email.

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