Background: Long-term, real-world effectiveness and safety data of disease-modifying treatments for spinal muscular atrophy (SMA) are important for assessing patient outcomes and providing information for a broader range of SMA patients than were included in clinical trials to date.
Objective: We sought to describe patients with SMA treated with onasemnogene abeparvovec monotherapy, including real-world effectiveness and safety outcomes.
Methods: RESTORE is a prospective, multicenter, multinational, observational registry that captures data from a variety of sources, including patients recruited de novo, patients treated during a clinical study who are not part of a long-term follow-up study, and patients from expanded/managed access programs.
Results: As of May 23, 2022, data were available for 168 patients treated with onasemnogene abeparvovec monotherapy. Median (IQR) age at initial diagnosis of SMA was 1 (0‒6) month. Median (IQR) age at onasemnogene abeparvovec infusion was 3 (1‒10) months. Eighty patients (47.6%) had two and 70 (41.7%) had three copies of SMN2, and 98 patients (58.3%) were identified by newborn screening. Patients achieved mean (SD) monthly increases in CHOP INTEND scores of 1.53 (1.54) and an overall mean (SD) change in score of 11.32 (8.35) from first to last assessment (mean [SD] time between first and last assessment was 8.8 [5.35] months). All patients maintained/achieved motor milestones. Adverse event (AE) data were reported for 167 patients: 81 (48.5%) experienced at least one treatment-emergent AE. A total of 31 patients (18.6%) experienced at least one serious AE, of which 8 of 31 were considered treatment-related).
Conclusions: Real-world outcomes of SMA patients treated with onasemnogene abeparvovec monotherapy in RESTORE support findings from the interventional trial program and demonstrate effectiveness over a large patient population, consistent with both initial clinical data and published 5-year (long-term) follow-up data. Observed AEs were consistent with the established safety profile of onasemnogene abeparvovec.