Written By: Pharmacally Medical News Desk
The U.S. Food and Drug Administration has approved AQVESME™ (mitapivat) for the treatment of anemia in adults with alpha- or beta-thalassemia, including both non-transfusion-dependent (NTDT) and transfusion-dependent (TDT) disease. Developed by Agios Pharmaceuticals, AQVESME becomes the only FDA-approved medicine specifically indicated to treat anemia across both forms of thalassemia.
Agios CEO Brian Goff described the approval as a landmark moment, emphasizing that AQVESME is the first medicine to address anemia across both transfusion-dependent and non-transfusion-dependent thalassemia. He acknowledged the contributions of patients, caregivers, clinicians, and advocacy groups in shaping the clinical development program.
About AQVESME (Mitapivat)
AQVESME is an oral pyruvate kinase (PK) activator designed to improve red blood cell energy metabolism and reduce hemolysis. By enhancing pyruvate kinase activity, mitapivat helps red blood cells function more efficiently, leading to higher hemoglobin levels and reduced anemia-related symptoms.
In the U.S., mitapivat will be marketed under two brand names:
- AQVESME™ for the thalassemia indication, which requires a REMS program
- PYRUKYND® for pyruvate kinase deficiency, which does not require REMS
Outside the U.S., mitapivat continues to be marketed as PYRUKYND for approved indications.
Clinical Evidence
The FDA approval is based on data from two global Phase 3 trials: ENERGIZE (NCT04770753) and ENERGIZE-T (NCT04770779), which evaluated mitapivat in adults with NTDT and TDT alpha- or beta-thalassemia, respectively.
The clinical program supporting AQVESME included two global Phase 3 studies designed as randomized, double-blind, placebo-controlled trials. Together, these studies enrolled 452 adult patients with alpha- or beta-thalassemia, reflecting a population that closely mirrors real-world clinical practice. Both trials met their primary efficacy endpoints in adults with non-transfusion-dependent and transfusion-dependent thalassemia, with significant improvements in hemoglobin in NTDT and reductions in transfusion burden in TDT.
Across the Phase 3 trials, AQVESME demonstrated significant improvements in hemoglobin levels, along with clinically meaningful reductions in transfusion burden among patients with transfusion-dependent thalassemia. Patients treated with AQVESME also reported improvements in fatigue, an important quality-of-life measure, reflecting better day-to-day functioning. Overall, mitapivat improved markers of hemolytic anemia, including hemoglobin levels and transfusion burden, compared with placebo. Investigators noted that these outcomes directly address core challenges of thalassemia that impact both daily living and long-term health.
Safety Profile
In the ENERGIZE and ENERGIZE-T Phase 3 trials, a small number of patients experienced hepatocellular injury, with some cases requiring hospitalization. Hepatocellular injury has been observed in patients treated with mitapivat at doses higher than those used for PK deficiency. These events occurred within the first six months of treatment, and liver function tests improved after discontinuation of AQVESME, indicating reversibility with appropriate management.
REMS Requirements
To mitigate the risk of hepatocellular injury, the U.S. FDA has required a Risk Evaluation and Mitigation Strategy (REMS) for AQVESME. The REMS program mandates liver function testing before initiating therapy, followed by monitoring every four weeks for the first 24 weeks of treatment and additional testing as clinically indicated thereafter. The program also includes education and certification requirements for prescribing physicians, pharmacists, and patients. Together, these measures are intended to support early detection of liver-related adverse events and ensure the safe use of AQVESME in clinical practice.
Peggy S. Blitz Endowed Chair in Hematology/Oncology at Mass General Brigham Cancer Institute, Associate Professor at Harvard Medical School, and an investigator for the mitapivat thalassemia Phase 3 clinical program, noted that the ENERGIZE trials show AQVESME can meaningfully improve anemia, fatigue, and reliance on transfusions, marking an important advance for patients who previously had limited or no treatment options.
Patient advocacy leaders like Ralph Colasanti, National President of the Cooley’s Anemia Foundation, also welcomed the decision, noting that this approval comes nearly a century after thalassemia was first described in medical literature and offers new hope, particularly for adults with non-transfusion-dependent disease who previously had no approved therapies.
Agios expects AQVESME to be available in the U.S. in late January 2026, following full implementation of the REMS program.
In addition to its development in thalassemia, mitapivat is being evaluated across other hemolytic anemias. Agios is studying mitapivat in sickle cell disease through the Phase 2/3 RISE UP clinical trial (NCT05031780)
References
U.S. FDA Approves Agios’ AQVESME™ (mitapivat) for the Treatment of Anemia in Adults with Alpha- or Beta-Thalassemia, 23 December 2025, https://investor.agios.com/news-releases/news-release-details/us-fda-approves-agios-aqvesmetm-mitapivat-treatment-anemia
A Study Evaluating the Efficacy and Safety of Mitapivat in Participants with Non-Transfusion-Dependent Alpha- or Beta-Thalassemia (α- or β-NTDT), ClinicalTrials.gov ID NCT04770753, https://clinicaltrials.gov/study/NCT04770753
Taher AT et al, Mitapivat in adults with non-transfusion-dependent α-thalassaemia or β-thalassaemia (ENERGIZE): a phase 3, international, randomised, double-blind, placebo-controlled trial. Lancet. 2025 Jul 5;406(10498):33-42. Doi: 10.1016/S0140-6736(25)00635-X. Epub 2025 Jun 19. PMID: 40544857.
A Study Evaluating the Efficacy and Safety of Mitapivat in Participants with Transfusion-Dependent Alpha- or Beta-Thalassemia (α- or β-TDT) (ENERGIZE-T), ClinicalTrials.gov ID NCT04770779, https://clinicaltrials.gov/study/NCT04770779
Maria Domenica Cappellini et al, ENERGIZE-T: A Global, Phase 3, Double-Blind, Randomized, Placebo-Controlled Study of Mitapivat in Adults with Transfusion-Dependent Alpha- or Beta-Thalassemia. Blood 2024; 144 (Supplement 1): 409. doi: https://doi.org/10.1182/blood-2024-200867