Outcomes for patients in the RESTORE registry with spinal muscular atrophy and four or more SMN2 gene copies treated with onasemnogene abeparvovec.

We describe outcomes following onasemnogene abeparvovec monotherapy for patients with ≥four survival motor neuron 2 (SMN2) gene copies in RESTORE, a noninterventional spinal muscular atrophy patient registry. We evaluated baseline characteristics, motor milestone achievement, post-treatment motor function, use of ventilatory/nutritional support, and adverse events as of December 22, 2022. At data cutoff, 19 patients in RESTORE had ≥four SMN2 copies and were treated with onasemnogene abeparvovec monotherapy (n=12 [63.2%] four copies; n=7 [36.8%] >four copies). All patients were identified by newborn screening and were reported as asymptomatic at diagnosis. Median age at onasemnogene abeparvovec administration was 3.0 months. Median time from treatment to last recorded visit was 15.4 months, with a range of post-treatment follow-up of 0.03-39.4 months. All 12 children who were assessed for motor development achieved new milestones, including standing alone (n=2) and walking alone (n=5). Five children reported one or more treatment-emergent adverse events (one Grade 3 or greater). No deaths or use of ventilatory/nutritional support were reported. Real-world findings from the RESTORE registry indicate that patients with ≥four SMN2 gene copies treated with onasemnogene abeparvovec monotherapy demonstrated improvements in motor function. Adverse events experienced by these patients were consistent with previously reported findings.

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Déclaration de conflit d'intérêts

Declaration of competing interest EFT received personal compensation for consultancy from Novartis Gene Therapies, Inc., Biogen, Biologiz, Cytokinetics, Novartis, and Roche, and research funding from Biogen/Ionis and Roche. SQ-R has participated in clinical trials sponsored by Roche, Novartis and Biogen, and has received speaker and/or consulting fees from Biogen, Novartis Gene Therapies, Inc. (AveXis), Sanofi, UCB, and Roche. She has received research support from the European Commission, INSERM-Health Ministry, and the Association Française des Myopathies (AFM). She is the scientific coordinator of the Registre SMA FRANCE for the French neuromuscular network (FILNEMUS) (http://filnemus.fr) and coordinator of the Garches-Necker-Creteil Health Care Provider for the European Reference Network for Rare Neuromuscular Diseases (ERN EURO-NMD). LS has received personal compensation from Novartis Gene Therapies, Inc., Biogen, Inc., Cytokinetics, Scholar Rock, Biohaven, Akros Pharma, Roche, and Illumina, and research funding from Novartis Gene Therapies, Inc., Biogen, Dynacure, and Roche. JAP has received clinical trial funding from AveXis/Novartis, Biogen, PTC Therapeutics, Sarepta Therapeutics, Biohaven, Genentech, and Scholar Rock, and served as advisor/consultant for AveXis, Biogen, Genentech, and Scholar Rock. SA is a site principal investigator for clinical trials of Biogen, Novartis Gene Therapies, Inc., and Roche; has participated on advisory boards for Novartis Gene Therapies, Inc./Novartis, and Roche; received speaker's fees from Biogen, Novartis, and Roche; and received a research grant from Novartis Gene Therapies, Inc. AL has served on advisory boards for AveXis and Biogen and received research funding from Novartis and Genentech. RSF has received personal compensation for advisory board/data safety monitoring board participation from Novartis Gene Therapies, Inc., Biogen, Catabasis, Ionis, ReveraGen, Roche/Genentech, and Scholar Rock; editorial fees from Elsevier for co-editing a neurology textbook; license fees from the Children's Hospital of Philadelphia; and research funding from Novartis Gene Therapies, Inc., Biogen, Catabasis, ReveraGen, Roche/Genentech, and Scholar Rock.