Sickle Cell Disease (SCD) is a chronic, progressive, and life-threatening inherited blood disorder that causes severe pain, anaemia, and organ damage. India accounts for 14.5% of the global burden of SCD, placing a heavy health, social, and economic burden on families. Traditionally, the disease has been managed through reactive emergency interventions during acute crises rather than through proactive, long-term care. For many patients, hydroxyurea remains the primary treatment option, while frequent blood transfusions and temporary pain management continue to define day-to-day care. Experts say there is an urgent need to move SCD management toward a continuous and preventive care model.
Against this backdrop, etavopivat, an investigational once-daily oral therapy, is being studied as a potential disease-modifying treatment for SCD. Unlike therapies that focus mainly on complications, etavopivat targets the underlying biology of the disease by acting on red blood cell metabolism. It works as a small-molecule activator of erythrocyte pyruvate kinase (PKR), an enzyme that helps maintain the shape, health, and function of red blood cells. By improving PKR activity, the therapy enhances the cell’s energy supply, supports healthier red blood cells, and increases oxygen affinity. This helps reduce sickling and haemolysis, while its once-daily oral dosing offers a more convenient option for long-term management.
Clinical evidence from the global Phase 3 HIBISCUS trial, which enrolled adolescent and adult participants across 17 countries, including India, has shown encouraging results. The study found that 48.7% of participants treated with etavopivat achieved a clinically relevant haemoglobin increase of more than 1 g/dL at week 24, compared to 7.2% in the placebo group. The therapy also reduced the annualised rate of vaso-occlusive crises by 27% on top of standard care. In addition, it prolonged the median time to a patient’s first VOC to 38.4 weeks, compared with 20.9 weeks for placebo, and preliminary analysis suggested a reduced risk of blood transfusions.
Speaking on the development, Dr. Dipty Jain, Director, Arihant Hospital and Ex-HOD, Department of Pediatrics, GMC Nagpur, said, “Etavopivat is a once-daily oral investigational therapy, showing promising progress in this area. Activating erythrocyte pyruvate kinase (PKR), it improves red blood cell metabolism, helping maintain healthier red blood cells while reducing sickling and haemolysis. In the Phase 3 HIBISCUS trial, etavopivat met its co-primary endpoints, demonstrating improvements in haemoglobin response and reductions in vaso-occlusive crises, while also delaying the onset of pain episodes and reducing reliance on blood transfusions. These advances have the potential to support a more proactive approach to SCD management and improve long-term patient outcomes, but it’s still undergoing clinical trials.”
Dr. Jina Bhattacharyya, Professor and Head of the Department of Clinical Hematology at Gauhati Medical College and Hospital, Guwahati, added, “For many years, the treatment of Sickle Cell Disease (SCD) has focused on managing symptoms and preventing complications. While existing therapies have improved survival and quality of life, many patients continue to experience recurrent pain crises, organ damage, and frequent hospitalisations, emphasising the need for more effective treatment options. Today, the SCD landscape is undergoing a significant transformation. Novel disease-modifying therapies are being developed to address the underlying biology of the disease by reducing red blood cell sickling, preventing vaso-occlusive crises, and limiting long-term complications. These advancements include targeted therapies, gene-based approaches such as gene addition and gene editing, and newer medicines designed to improve blood flow and reduce inflammation.”
As SCD care evolves, etavopivat represents a promising step toward more proactive, continuous disease management. If approved, it could help address treatment gaps and improve access to a sustainable oral therapy for patients living with the condition.
