FDA Approves Milestone Oral Therapy for Adults With Thalassemia Anemia

The FDA approved mitapivat (Aqvesme; Agios) for the treatment of anemia in adults with α- or β-thalassemia. This landmark decision marks the first medication indicated for both transfusion-dependent and non–transfusion-dependent forms of these rare, inherited blood disorders.¹

“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,” Brian Goff, CEO of Agios, said in a news release. “With this approval, Aqvesme becomes the only medicine indicated for the treatment of anemia in both non-transfusion-dependent and transfusion-dependent α- or β-thalassemia.”¹

Understanding Thalassemia

Mitapivat is an oral pyruvate kinase (PK) activator, targeting the underlying mechanisms that lead to shortened red blood cell lifespans. In the US, approximately 6000 adults are diagnosed with thalassemia, a condition characterized by genetic defects in the synthesis of globin chains. These imbalances cause hemolysis and impair erythropoiesis, leading to chronic anemia, debilitating fatigue, and life-threatening complications.^1,2

“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,” Hanny Al-Samkari, MD, an investigator in the mitapivat thalassemia phase 3 clinical program and Peggy S. Blitz Endowed Chair in Hematology/Oncology at Mass General Brigham Cancer Institute, said in a news release.¹

The disease has historically been categorized by its severity and the specific globin chain affected. Alpha-thalassemia stems from deficient α globin synthesis, whereas β-thalassemia involves reduced β globin production. For many, the only management option was regular, lifelong blood transfusions to maintain hemoglobin levels, which inevitably leads to iron overload and damage to the heart or liver. Others with non–transfusion-dependent forms often had no approved pharmacological alternatives to address the chronic strain on their bodies.^1,2

“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,” Al-Samkari said. “Today’s FDA approval represents an important step forward for individuals with thalassemia.”¹

The ENERGIZE and ENERGIZE-T Trials

The FDA’s decision was bolstered by data from the ENERGIZE (NCT04770753) and ENERGIZE-T (NCT04770779) phase 3 trials. These global studies involved 452 patients and demonstrated that mitapivat significantly improved hemoglobin levels and reduced fatigue scores compared to a placebo.¹

In the ENERGIZE-T trial, which focused on transfusion-dependent patients, the drug achieved a meaningful reduction in transfusion burden, with some participants achieving transfusion independence. These results represent a significant shift for patients who otherwise faced a lifetime of clinical visits and chelation therapy to remove excess iron.¹

Despite its efficacy, mitapivat carries a boxed warning regarding hepatocellular injury. During clinical trials, some patients experienced liver injury, with 2 individuals requiring hospitalization. Consequently, the drug is available only through a Risk Evaluation and Mitigation Strategy program, which mandates that physicians and pharmacists be certified and requires patients to undergo liver laboratory tests every 4 weeks for the first 6 months of treatment to ensure safety.¹

Agios Pharmaceuticals expects the treatment to be available in the US by late January 2026.¹

“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 of the Cooley’s Anemia Foundation, in a news release. “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.”¹

REFERENCES

1. US FDA approves Agios’ Aqvesme (mitapivat) for the treatment of anemia in adults with alpha- or beta-thalassemia. News release. Agios Pharmaceuticals. December 23, 2025. Accessed December 24, 2025. https://investor.agios.com/news-releases/news-release-details/us-fda-approves-agios-aqvesmetm-mitapivat-treatment-anemia

2. Muncie HL, Campbell JS. Alpha and beta thalassemia. Am Fam Physician. 2009;80(4):339-344.