Objective: We sought to assess treatment patterns and long-term, real-world outcomes in patients with SMA in the context of expanding disease-modifying treatment options.
Background: While three disease-modifying therapies have been approved for SMA, real-world data on treatment outcomes are limited.
Methods: RESTORE is a prospective, multicenter, multinational, observational registry that captures data on patients with SMA from several sources (e.g., patients recruited de novo, patients previously treated during a clinical study who were not part of a long-term follow-up study, and patients from expanded/managed access programs).
Results: As of May 23, 2021, data were available for 247 patients (215 from the US, 19 from Japan, 5 from Ireland, 4 from Israel, and 4 from Portugal). Therapeutic regimens were: onasemnogene abeparvovec monotherapy (n=110); switching to onasemnogene abeparvovec after initial nusinersen (n=61); combinations with onasemnogene abeparvovec (n=41); nusinersen or risdiplam monotherapy (n=29); nusinersen switched to risdiplam (n=3); and supportive care only (n=3). Most patients (146/247 [59.1%]) had two copies of the SMN2 gene. In the onasemnogene abeparvovec monotherapy, nusinersen switching to onasemnogene abeparvovec, and combinations with onasemnogene abeparvovec therapy groups, patients achieved mean (SD) monthly increases in CHOP INTEND scores of 1.4 (1.0), 1.2 (1.3), and 1.4 (2.1) points, respectively. Across treatment groups, patients achieved motor milestones. Adverse-event (AE) data were reported for 244 patients; 117 (48.0%) reported at least one treatment-emergent AE while 53 (21.7%) indicated at least one serious AE (22 [9.0%] related to onasemnogene abeparvovec treatment).
Conclusions: RESTORE provides extended real-world assessments of patient outcomes and SMA interventions gathered from routine clinical practice. Based on data available to date, the AE experience of onasemnogene abeparvovec in RESTORE is consistent with experience previously described for SMA. No new safety signals were identified in patients treated with onasemnogene abeparvovec or in those who switched to onasemnogene abeparvovec from prior treatment.