Agios Pharmaceuticals announced that the US Food and Drug Administration (FDA) has approved AQVESME (mitapivat), an oral Pyruvate Kinase (PK) activator, for the treatment of anaemia in adults with alpha- or beta-thalassemia. With this approved indication, AQVESME becomes the only FDA-approved medicine for anaemia 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. The ENERGIZE and ENERGIZE-T phase III trial results demonstrate that AQVESME can help address anaemia, 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,” said Hanny Al-Samkari, MD, 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 III clinical programme.

The FDA approval of AQVESME in thalassemia is based on results from the global, randomised, double-blind, placebo-controlled ENERGIZE and ENERGIZE-T phase III 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 III trials met all primary and key secondary efficacy endpoints, demonstrating that AQVESME improves hemolytic anaemia and a key quality-of-life measure compared to placebo, including significant reductions in transfusion burden and significant improvements in haemoglobin 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. With this approval, AQVESME becomes the only medicine indicated for the treatment of anaemia 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,” said Brian Goff, Chief Executive Officer, Agios.

In the ENERGIZE and ENERGIZE-T phase III trials, five patients receiving AQVESME experienced adverse reactions suggestive of hepatocellular injury (HCI), with two of these patients requiring hospitalisation. 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) programme approved by the FDA. The AQVESME REMS programme 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, who are common components of REMS programmes.

“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. 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 US, including those with non-transfusion-dependent thalassemia who previously had no approved alternatives,” said Ralph Colasanti, National President, Cooley’s Anemia Foundation.

Due to the AQVESME REMS programme, mitapivat will be marketed under the brand name AQVESME in the US for the thalassemia indication. Mitapivat will continue to be marketed as PYRUKYND (mitapivat) in the US for the PK deficiency indication, which does not require a REMS programme. Outside the US, 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 US in late January 2026, following implementation of the AQVESME REMS programme.