Respiratory outcomes of onasemnogene abeparvovec treatment for spinal muscular atrophy: national real-world cohort study.

Abstract

Onasemnogene abeparvovec (OA) is a novel gene replacement therapy for patients with spinal muscular atrophy (SMA). This study provides real-world respiratory data for pediatric SMA patients receiving OA who were assessed before and one year after treatment in a multicenter cohort study conducted from 2019 to 2021. Twenty-five OA-treated SMA patients (23 with type 1 and 2 with type 2; median age at treatment 6.1 months, with a range of 0.36-23 months) were included. Sixteen were treatment-naïve, and nine had received various prior treatments. Two patients died due to respiratory failure during the study period. Of the remaining 23 patients, four were put on non-invasive ventilation (NIV), bringing ventilated patients to a total of ten during the post-treatment year. Three patients required permanent NIV support, while 13 did not require any respiratory support. Ventilation time decreased from 14.3 to 11.1 hours per day, and respiratory hospitalizations decreased by 26% (from 0.76 to 0.57 per life year). Fifteen of the 23 patients maintained full oral nutrition at study closure compared to 20 of the 25 at study initiation. This real-world data analysis demonstrates that OA may improve respiratory outcomes in SMA patients. Importantly, compounding factors, such as age at treatment initiation, treatment combinations, and natural history, may influence the respiratory course, thus highlighting the need for standardized long-term management. What is Known: • Respiratory failure is a leading cause of mortality in untreated spinal muscular atrophy type 1 patients. • Onasemnogene abeparvovec (OA) improves neurological outcomes, but real-world respiratory data are limited. What is New: • Our real-world analysis suggests OA may improve respiratory outcomes. • Age at treatment and treatment combinations may also influence respiratory trajectory.