P68 Outcomes in Patients with Spinal Muscular Atrophy (SMA) and Four or More SMN2 Copies Treated with Onasemnogene Abeparvovec: Findings from RESTORE

Onasemnogene abeparvovec is a one-time gene replacement therapy for SMA. While clinical trials of onasemnogene abeparvovec included patients with two or three SMN2 gene copies, patients with ≥4 copies may be treated in clinical practice. Natural history and outcomes following SMA treatment have not been well-characterized for these patients. We sought to describe clinical outcomes after onasemnogene abeparvovec monotherapy for patients with ≥4 SMN2 copies in RESTORE, a comprehensive, noninterventional SMA registry. We evaluated baseline characteristics, and post-treatment motor function, motor milestone achievement, use of ventilatory/nutritional support, and AEs (as of Dec. 22, 2022, data cut). Patients evaluable for motor function or milestone achievement had ≥2 assessments, with at least 1 occurring after onasemnogene abeparvovec administration. Twelve children with 4 SMN2 copies and 7 with ≥4 copies were included. All 19 cases were identified by newborn screening and all but one were treated presymptomatically. Median age at onasemnogene abeparvovec administration was 3.0 (range, 1–11) months. Twelve children with evaluable motor milestone assessments achieved new milestones. Seven of 13 children evaluable for CHOP INTEND maintained or achieved the maximum score of 64 points. Five children with recorded AE data had ≥1 treatment-emergent AE. One child reported AE ≥Grade 3 (history of seizure ≃3.5 months post-onasemnogene abeparvovec administration). No deaths or use of ventilatory or nutritional support were reported. Patients with ≥4 SMN2 copies attained improvements in motor function and achieved new milestones after treatment with onasemnogene abeparvovec. SMA presentation with ≥4 SMN2 copies is heterogeneous, and laboratory determination of SMN2 copy number may be unreliable, highlighting the importance of early identification and intervention to optimize outcomes for all SMA patients. Onasemnogene abeparvovec is a one-time gene replacement therapy for SMA. While clinical trials of onasemnogene abeparvovec included patients with two or three SMN2 gene copies, patients with ≥4 copies may be treated in clinical practice. Natural history and outcomes following SMA treatment have not been well-characterized for these patients. We sought to describe clinical outcomes after onasemnogene abeparvovec monotherapy for patients with ≥4 SMN2 copies in RESTORE, a comprehensive, noninterventional SMA registry. We evaluated baseline characteristics, and post-treatment motor function, motor milestone achievement, use of ventilatory/nutritional support, and AEs (as of Dec. 22, 2022, data cut). Patients evaluable for motor function or milestone achievement had ≥2 assessments, with at least 1 occurring after onasemnogene abeparvovec administration. Twelve children with 4 SMN2 copies and 7 with ≥4 copies were included. All 19 cases were identified by newborn screening and all but one were treated presymptomatically. Median age at onasemnogene abeparvovec administration was 3.0 (range, 1–11) months. Twelve children with evaluable motor milestone assessments achieved new milestones. Seven of 13 children evaluable for CHOP INTEND maintained or achieved the maximum score of 64 points. Five children with recorded AE data had ≥1 treatment-emergent AE. One child reported AE ≥Grade 3 (history of seizure ≃3.5 months post-onasemnogene abeparvovec administration). No deaths or use of ventilatory or nutritional support were reported. Patients with ≥4 SMN2 copies attained improvements in motor function and achieved new milestones after treatment with onasemnogene abeparvovec. SMA presentation with ≥4 SMN2 copies is heterogeneous, and laboratory determination of SMN2 copy number may be unreliable, highlighting the importance of early identification and intervention to optimize outcomes for all SMA patients.