Fatal outcomes following onasemnogene abeparvovec in advanced-stage spinal muscular atrophy

Abstract

Objective Supported by encouraging trial outcomes, onasemnogene abeparvovec (OA) was authorized for treating spinal muscular atrophy (SMA) in children under 2 years of age. Nevertheless, the efficacy of OA in advanced SMA patients remains underexplored. This investigation assessed the clinical effectiveness and adverse effects of OA in a patient cohort including those with advanced SMA, and compared these outcomes to historical survival data for SMA type 1 patients in Thailand. Methods We conducted an observational cohort study at Siriraj Hospital, Thailand, from May 2019 to April 2022. The study enrolled eight SMA patients receiving OA therapy. We monitored safety through laboratory tests and clinical evaluations. Patient outcomes, such as motor scores, motor milestones, and survival status, were analyzed. Results The cohort comprised five SMA type 1 patients treated at median age of 16.7 months (6.5–24.9 months) and three SMA type 2 patients treated at median age of 20.3 months (19–31.5 months). Before receiving OA, all type 1 patients needed invasive ventilation and nutritional support by feeding tubes. Posttreatment, these patients did not achieve new motor milestones, their survival rates remained static, and each patient experienced severe adverse events, including fatalities. Conversely, type 2 patients exhibited improved motor scores without experiencing serious adverse events. Interpretation: This real-world evaluation revealed that OA did not significantly improve outcomes or survival rates among advanced SMA type 1 patients, with all such cases resulting in mortality. These findings suggest the need for additional caution and revised guidelines when administering OA to this subgroup.