Real-World Outcomes in Patients with Spinal Muscular Atrophy Treated with Onasemnogene Abeparvovec Monotherapy: Findings from the RESTORE Registry

J Neuromuscul Dis. 2024;11(2):425-442. doi: 10.3233/JND-230122.


Background: Long-term, real-world effectiveness and safety data of disease-modifying treatments for spinal muscular atrophy (SMA) are important for assessing outcomes and providing information for a larger number and broader range of SMA patients than included in clinical trials.

Objective: We sought to describe patients with SMA treated with onasemnogene abeparvovec monotherapy in the real-world setting.

Methods: RESTORE is a prospective, multicenter, multinational, observational registry that captures data from a variety of sources.

Results: Recruitment started in September 2018. As of May 23, 2022, data were available for 168 patients treated with onasemnogene abeparvovec monotherapy. Median (IQR) age at initial SMA diagnosis was 1 (0-6) month and 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 (58.3%) were identified by newborn screening. Infants identified by newborn screening had a lower age at final assessment (mean age 11.5 months) and greater mean final (SD) CHOP INTEND score (57.0 [10.0] points) compared with clinically diagnosed patients (23.1 months; 52.1 [8.0] points). All patients maintained/achieved motor milestones. 48.5% (n = 81/167) experienced at least one treatment-emergent adverse event (AE), and 31/167 patients (18.6%) experienced at least one serious AE, of which 8/31 were considered treatment-related.

Conclusion: These real-world outcomes support findings from the interventional trial program and demonstrate effectiveness of onasemnogene abeparvovec over a large patient population, which was consistent with initial clinical data and published 5-year follow-up data. Observed AEs were consistent with the established safety profile of onasemnogene abeparvovec.

Keywords: AAV9 vector-based gene replacement therapy; RESTORE registry; long-term follow-up; motor neuron disease; newborn screening; onasemnogene abeparvovec; outcomes; rare disease; real-world evidence; spinal muscular atrophy.

Publication types

  • Multicenter Study

MeSH terms

  • Biological Products*
  • Genetic Therapy
  • Humans
  • Infant
  • Infant, Newborn
  • Muscular Atrophy, Spinal* / drug therapy
  • Prospective Studies
  • Recombinant Fusion Proteins*
  • Registries
  • Spinal Muscular Atrophies of Childhood* / drug therapy


  • Zolgensma
  • Biological Products
  • Recombinant Fusion Proteins