Agios Pharmaceuticals, Inc. (Nasdaq: AGIO), a commercial-stage biopharmaceutical company focused on delivering innovative medicines for patients with rare diseases, announced the U.S. Food and Drug Administration (FDA) approval of Aqvesme (mitapivat), an oral pyruvate kinase (PK) activator, for the treatment of anemia in adults with alpha- or beta-thalassemia. With this approved indication, Aqvesme becomes the only FDA-approved medicine for anemia in both non-transfusion-dependent and transfusion-dependent alpha- or beta-thalassemia.
“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,” said Hanny Al-Samkari, M.D., 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. “The ENERGIZE and ENERGIZE-T Phase 3 trial results demonstrate that Aqvesme can help address anemia, fatigue, and the need for regular transfusions – key challenges of the disease. Today’s FDA approval represents an important step forward for individuals with thalassemia.”
The FDA approval of Aqvesme in thalassemia is based on results from the global, randomized, double-blind, placebo-controlled ENERGIZE and ENERGIZE-T Phase 3 trials in adults with non-transfusion-dependent and transfusion-dependent alpha- or beta-thalassemia, respectively. A total of 452 patients who are representative of the real-world thalassemia population were enrolled in the trials. The ENERGIZE and ENERGIZE-T Phase 3 trials met all primary and key secondary efficacy endpoints, demonstrating that Aqvesme improves hemolytic anemia and a key quality-of-life measure compared to placebo, including significant reductions in transfusion burden and significant improvements in hemoglobin and fatigue.
“Today is a landmark moment for the thalassemia community, bringing forward an innovative, disease-modifying oral medicine to address the urgent needs of people living with this devastating rare blood disorder,” said Brian Goff, Chief Executive Officer, Agios. “With this approval, Aqvesme becomes the only medicine indicated for the treatment of anemia in both non-transfusion-dependent and transfusion-dependent alpha- or beta-thalassemia. We are deeply grateful to the patients, caregivers, healthcare providers, and advocacy partners who participated in and supported our clinical trials and helped ensure that our efforts reflected their priorities. Our focus now is on ensuring a successful launch and delivering meaningful impact for the community.”
“This year marks 100 years since thalassemia was first described in medical literature, and the progress we’ve made as a community is truly extraordinary,” said Ralph Colasanti, National President, Cooley’s Anemia Foundation. “Innovative medicines like Aqvesme help make this progress possible, offering new hope to patients like me by helping to address the complex needs and challenges of this disease. This approval provides an important new treatment option for the thousands of adults living with thalassemia in the U.S., including those with non-transfusion-dependent thalassemia who previously had no approved alternatives.”
In the ENERGIZE and ENERGIZE-T Phase 3 trials, five patients receiving Aqvesme experienced adverse reactions suggestive of hepatocellular injury (HCI), with two of these patients requiring hospitalization. These adverse reactions occurred within the first six months of exposure, and liver tests improved upon discontinuation of Aqvesme. To mitigate the risk of HCI, Aqvesme is available only through the Aqvesme REMS, a Risk Evaluation and Mitigation Strategy (REMS) program approved by the FDA. The Aqvesme REMS program requires liver tests prior to the first Aqvesme dose, every four weeks thereafter for 24 weeks, and then as clinically indicated. It also includes education and certification requirements for patients, prescribing physicians, and pharmacists, which are common components of REMS programs.
Due to the Aqvesme REMS program, mitapivat will be marketed under the brand name Aqvesme in the U.S. for the thalassemia indication. Mitapivat will continue to be marketed as Pyrukynd® (mitapivat) in the U.S. for the PK deficiency indication, which does not require a REMS program. Outside the U.S., mitapivat will continue to be marketed as Pyrukynd for its PK deficiency and thalassemia indications in regions where it is approved, and will retain this name upon approval in regions currently under regulatory review.
Agios expects Aqvesme to be available in the U.S. in late January 2026, following implementation of the Aqvesme REMS program. For more information, visit Aqvesme.com.
Some individuals with thalassemia require regular transfusions (classified as transfusion-dependent thalassemia), while others only need them intermittently (classified as non-transfusion-dependent thalassemia). All patients with thalassemia experience a significant disease burden, including comorbidities, reduced quality of life, and shortened life expectancy.
In the U.S., approximately 6,000 adult patients are diagnosed with thalassemia.
The ENERGIZE trial randomized 194 non-transfusion-dependent alpha- or beta-thalassemia patients 2:1 to receive either mitapivat 100 mg twice daily or placebo. The primary endpoint was hemoglobin response, defined as an increase of ≥1.0 g/dL in average hemoglobin concentration from Week 12 through Week 24 compared with baseline. Key secondary endpoints included changes from baseline in average fatigue scores and in average hemoglobin concentration from Week 12 to Week 24. The trial also assessed safety and tolerability.
The ENERGIZE-T trial randomized 258 transfusion-dependent alpha- or beta-thalassemia patients 2:1 to receive either mitapivat 100 mg twice daily or placebo. The primary endpoint was transfusion reduction response, defined as a ≥50% reduction in transfused red blood cell (RBC) units with a reduction of ≥2 units of RBCs transfused in any consecutive 12-week period through Week 48 compared with baseline. Several transfusion reduction measures were included as key secondary endpoints, and achievement of transfusion independence was a secondary endpoint. The trial also assessed safety and tolerability.
For each trial, patients who completed the double-blind phase had the option to transition into a corresponding open-label extension phase, during which all patients receive mitapivat.
