In a defining breakthrough for the global fight against thalassaemia, the US Food and Drug Administration (FDA) has approved the first-ever oral pill to treat anaemia in adults with the inherited blood disorder, offering fresh hope to lakhs of patients dependent on lifelong blood transfusions.
Developed by Agios Pharmaceuticals, AQVESME (mitapivat) is a first-of-its-kind oral pyruvate kinase (PK) activator designed to improve red blood cell energy balance, reduce hemolysis and decrease transfusion dependency. The approval has been granted on the basis of data from the global Phase 3 Energize and Energize-T trials, which evaluated its efficacy in both non-transfusion-dependent (NTDT) and transfusion-dependent (TDT) alpha and beta thalassaemia.
Mitapivat acts by activating the pyruvate kinase enzyme, which plays a crucial role in energy production within red blood cells. The drug improves cellular energy levels, stabilises red blood cells and reduces their premature destruction by enhancing PK activity.
Unlike conventional therapies that primarily address symptoms, mitapivat targets the underlying metabolic dysfunction within red blood cells. In clinical trials, it demonstrated a 40-50% efficacy rate in reducing transfusion requirements among adults with thalassemia.
Although it is yet to get the nod of Drugs Controller General of India (DCGI) and available in the country, experts believe that the emergence of an effective oral therapy like Mitapivat, combined with existing affordable treatments such as thalidomide and luspatercept, could significantly ease the treatment burden for thousands of thalassaemia patients in India while paving the way for more accessible, patient-friendly care.
Beyond gene therapy
Indian College of Haematology (ICH) secretary Prof RK Jena described the FDA approval as a potential game-changer in long-term disease management. “Every patient may not be able to afford BMT or cellular therapy and frequent blood transfusions often lead to iron overload and damage to vital organs and endocrine systems. If an oral medication can meaningfully reduce transfusion requirements, nothing is better than this,” he said.
Prof Jena, who was part of India’s first-ever study on thalidomide as a potent haemoglobin inducer, believes mitapivat could complement existing affordable therapies for reducing transfusion dependence by increasing foetal haemoglobin production.
The Indian College of Haematology has recommended thalidomide at a dose of 2-4mg per kg of body weight for thalassemia patients. “Thalassemia management is rapidly evolving with newer drugs like luspatercept and mitapivat that help reduce transfusion needs. Luspatercept is available in the form of injection in India and mitapivat is expected anytime soon. But these are not replacements of BMT and gene therapy, which offer a potential cure. With multidisciplinary care and advancing therapies, patients can expect improved survival, quality of life, and future hope for definitive treatment,” said Dr Mukul Aggarwal, associate professor of clinical haematology at AIIMS-Delhi.