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

Supported by encouraging trial outcomes, onasemnogene abeparvovec (OA) was authorized for spinal muscular atrophy (SMA). Nevertheless, efficacy of OA in advanced SMA patients remains underexplored. This investigation assessed clinical effectiveness and adverse effects of OA in a cohort including advanced SMA, and compared to historical survival data for SMA type 1 patients in Thailand. We conducted observational cohort study at Siriraj Hospital, Thailand, from May 2019 to April 2022. The study enrolled eight SMA patients receiving OA therapy. The cohort comprised five SMA type 1 patients treated at 16.7 months (6.5-24.9 months) and three SMA type 2 patients treated at 20.3 months (19-31.5 months). Before receiving OA, all Type 1 patients required 24-hour invasive ventilation and feeding support. Post-treatment, Three of five showed gradual improvement in motor scores, but none achieved new motor milestones. Survival rate was not improved, with all experiencing fatalities. Conversely, Type 2 patients exhibited motor score improvement without serious adverse events. OA did not significantly improve clinical outcomes or survival rates in advanced Type 1 SMA. These findings highlight need for additional caution when administering OA to severe SMA Type 1 and more specific guidelines in selecting subgroups for treatment.