Oncology/Hematology
>
Anemia
— PK activator indicated for adults with alpha- or beta-thalassemia
by Ian Ingram, Managing Editor, MedPage Today
December 24, 2025 • 2 min read
The FDA approved mitapivat (Aqvesme) as a disease-modifying treatment for anemia in adults with alpha- or beta-thalassemia, a rare inherited blood disease that affects hemoglobin production.
An oral pyruvate kinase (PK) activator, mitapivat becomes the only approved option for treating anemia in both non-transfusion- and transfusion-dependent patients with alpha- or beta-thalassemia, according to drugmaker Agios Pharmaceuticals, which announced the approval on Tuesday.
Labeling includes a boxed warning over the risk of serious liver injury, and the product will be available under a risk evaluation and mitigation strategy (REMS) program.
Approval was supported by ENERGIZE and ENERGIZE-T, global phase III placebo-controlled trials involving 452 patients with alpha- or beta-thalassemia. The studies demonstrated significant improvements in hemoglobin response, transfusion burden, and fatigue with mitapivat.
“Thalassemia is a debilitating disease that demands lifelong management and vigilant monitoring for many life-threatening complications, such as blood clots, heart disease, and liver disease. Despite its severity, treatments have historically been limited, leaving some patients without any options,” investigator Hanny Al-Samkari, MD, of Mass General Brigham Cancer Institute and Harvard Medical School in Boston, said in a statement.
The trial “results demonstrate that Aqvesme can help address anemia, fatigue, and the need for regular transfusions — key challenges of the disease,” Al-Samkari added.
In ENERGIZE and ENERGIZE-T, five of the participants randomized to mitapivat had adverse events (AEs) suggestive of liver injury within 6 months of starting treatment; two required hospitalization.
As part of the REMS program, liver function testing (aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, and bilirubin) is required before starting treatment, every 4 weeks for 6 months, and then as clinically indicated. Use of mitapivat should be avoided in patients with cirrhosis.
Common AEs with mitapivat reported in the thalassemia trials included headache and insomnia. Prescribing information also includes warnings of drug interactions with CYP3A inhibitors and inducers; sensitive CYP3A substrates; and CYP2B6, CYP2C, UGT1A1, and P-gp substrates.
Mitapivat was also approved in 2022 for treating hemolytic anemia in adults with PK deficiency, under the brand name Pyrukynd.
