Onasemnogene Abeparvovec in Early-Onset Spinal Muscular Atrophy: An Indian Experience

Abstract Background and Objectives: Spinal muscular atrophy (SMA) is an inherited neuromuscular disorder with a grave prognosis. Gene replacement therapy has significantly altered the disease trajectory. This study presents real-world evidence of the efficacy and safety of onasemnogene abeparvovec (OA) in children below 2 years of age from India. Methods: This single-centre, prospective cohort study includes longitudinal data of patients treated with OA for over 18 months. All patients diagnosed with SMA under 2 years of age were enrolled for OA through either the Global Managed Access Program or via commercial procurement. Once selected, patients were admitted for OA infusion, with close monitoring for adverse effects and blood parameters. Patients were followed prospectively to assess motor milestones and functional motor scores, ventilator and feeding support requirements, and hospitalization frequency. Results: Thirteen children received OA over the study period. Three died within a month—two likely due to the severity of the underlying disease and one from an unknown cause. Transaminitis and transient thrombocytopenia were frequently observed but managed successfully. Most patients showed gains in motor milestones during follow-up; the remainder maintained their baseline. No new ventilatory or feeding support was required. One child was weaned from permanent ventilation and gastrostomy to predominantly oral feeding, and another transitioned from nasogastric to oral feeds. Caregivers reported clinically meaningful improvement in 50% of patients. Conclusions: OA has transformed the landscape for children with early-onset SMA, enabling the achievement of motor milestones previously considered unattainable. However, the chronic nature of the disease necessitates long-term multidisciplinary care.