The Food and Drug Administration (FDA) has approved Pyrukynd® (mitapivat) for the treatment of hemolytic anemia in adults with pyruvate kinase deficiency.
Pyruvate kinase (PK) deficiency is a rare, inherited disease caused by mutations in the PKLR gene resulting in a deficiency of the enzyme pyruvate kinase. The disease is characterized by an accelerated destruction of red blood cells. Pyrukynd is a first-in-class, oral, selective PK activator.
The approval was based on data from two phase 3 studies, ACTIVATE (ClinicalTrials.gov Identifier: NCT03548220) and ACTIVATE-T (ClinicalTrials.gov Identifier: NCT03559699), which evaluated the efficacy and safety of mitapivat in adults with PK deficiency not regularly transfused and regularly transfused, respectively.
The ACTIVATE study included 80 patients who were randomly assigned 1:1 to receive either mitapivat or placebo for an average duration of about 24 weeks; ACTIVATE-T included 27 patients who received mitapivat for an average duration of about 40 weeks. In both studies, patients received mitapivat 50mg orally twice daily after an initial dose titration period.
Results from ACTIVATE showed that 40% (n=16) of patients treated with mitapivat achieved a hemoglobin (Hb) response (primary endpoint), defined as at least an increase of 1.5g/dL in Hb from baseline sustained at 2 or more scheduled assessments (weeks 16, 20, and 24) during the fixed dose period without transfusions, compared with 0 patients in the placebo arm (P <.0001). Statistically significant improvements were also observed in markers of hemolysis and ineffective erythropoiesis.
Findings from ACTIVATE-T showed that 33% (n=9) of patients treated with mitapivat had a transfusion reduction response (primary endpoint), defined as at least a 33% reduction in transfusion burden, in the 24-week fixed dose period compared with historical transfusion burden. Moreover, all 6 (22%) patients who were transfusion-free during the 24 weeks remained transfusion free in a long-term extension study. The median duration of response for the 6 patients was 17 months (range, 11.5+, 21.8+).
“The successful ACTIVATE and ACTIVATE-T studies demonstrate the impact of mitapivat in significantly improving hemolysis and anemia in PK deficiency,” said Hanny Al-Samkari, MD, hematologist and clinical investigator at the Mass General Cancer Center and Harvard Medical School, and an investigator in these pivotal phase 3 studies. “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.”
The most common adverse reactions reported with mitapivat were decreased estrone (males), increased urate, back pain, decreased estradiol (males), and arthralgia. Acute hemolysis with subsequent anemia was also observed following abrupt interruption or discontinuation of mitapivat in a dose-ranging study.
Pyrukynd is supplied as 5mg, 20mg, and 50mg tablets. The treatment is expected to be available in approximately 2 weeks. The Company is also offering an assistance program to help eligible patients.
- FDA approves treatment for anemia in adults with rare inherited disorder. News release. US Food and Drug Administration. Accessed February 17, 2022. https://www.fda.gov/drugs/news-events-human-drugs/fda-approves-treatment-anemia-adults-rare-inherited-disorder
- Agios announces FDA approval of Pyrukynd® (mitapivat) as first disease-modifying therapy for hemolytic anemia in adults with pyruvate kinase deficiency. News release. Agios Pharmaceuticals, Inc. Accessed February 17, 2022. https://www.globenewswire.com/news-release/2022/02/17/2387542/0/en/Agios-Announces-FDA-Approval-of-PYRUKYND-mitapivat-as-First-Disease-Modifying-Therapy-for-Hemolytic-Anemia-in-Adults-with-Pyruvate-Kinase-Deficiency.html
- Pyrukynd. Package insert. Agios Pharmaceuticals, Inc.; 2022. Accessed February 17, 2022. https://www.accessdata.fda.gov/drugsatfda_docs/label/2022/216196s000lbl.pdf