[en] [en] OBJECTIVE: 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.
METHODS: We evaluated baseline characteristics, motor milestone achievement, post-treatment motor function, use of ventilatory/nutritional support, and adverse events as of December 22, 2022.
RESULTS: 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.
CONCLUSIONS: 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.
Disciplines :
Pediatrics
Author, co-author :
Tizzano, Eduardo F; Department of Clinical and Molecular Genetics, Hospital Vall d'Hebron, Passeig de la Vall d'Hebron, 119-129, Horta-Guinardó, 08035, Barcelona, Spain. Electronic address: eduardo.tizzano@vallhebron.cat
Quijano-Roy, Susana; Garches Neuromuscular Reference Center, APHP Raymond Poincaré University Hospital (UVSQ Paris Saclay), 104 Bd Raymond Poincaré, 92380, Garches, France
Servais, Laurent ; Université de Liège - ULiège > Département des sciences cliniques
Parsons, Julie A; Children's Hospital Colorado, University of Colorado School of Medicine, 13001 East 17th Place, Aurora, CO, 80045, USA
Aharoni, Sharon; Institute of Pediatric Neurology, Schneider Children's Medical Center of Israel, Kaplan St 14, Petah Tikva, Israel, Faculty of Medical and Health Sciences, Tel-Aviv University, Ramat Aviv, Tel Aviv, Israel
Lakhotia, Arpita; University of Louisville, Norton Children's Medical Group, 411 East Chestnut Street, Floor 6, Louisville, KY, 40202, USA
Finkel, Richard S; Center for Experimental Neurotherapeutics, St. Jude Children's Research Hospital, 262 Danny Thomas Place, Memphis, TN, 38105, USA
RESTORE Study Group
Language :
English
Title :
Outcomes for patients in the RESTORE registry with spinal muscular atrophy and four or more SMN2 gene copies treated with onasemnogene abeparvovec.
NGT - Novartis Gene Therapies WHO - World Health Organization
Funding text :
Motor milestones were assessed using criteria from the World Health Organization (WHO) [41,42] and Bayley Scales of Infant and Toddler Development, Third Edition (BSID) [43]. Ten select performance criteria were used to define the achievement of developmental milestones on the case report form, specifically: holds head erect 3 s; rolls from back to sides; sits independently without support for >10 s (WHO); sits independently without support for \u226530 s (BSID); stands with assistance; crawls forward \u22655 feet; pulls to stand; walks with assistance; stands alone; and walks alone five or more steps (WHO). The interval for each collection was dependent on routine follow-up visits [39]. Because no predetermined follow-up was scheduled, motor milestones may not have been recorded at every visit, and age of first recorded milestone achievement may not reflect true age at first achievement.Writing and editing assistance, including preparation of a draft manuscript under the direction and guidance of the authors, incorporating author feedback, and manuscript submission, was provided by Wynne Dillon, MS, Caryne Craige, PhD (Kay Square Scientific, Newtown Square, PA, USA), and David Wolff, MS (Novartis Gene Therapies, Inc. Bannockburn, IL, USA). This support was funded by Novartis Gene Therapies, Inc. The authors wish to thank Dr. Simona Treidler from Stony Brook Children's, Stony Brook, NY, USA, for her critical review and input of her patient's details included in this manuscript. The authors also wish to thank the RESTORE investigators and site coordinators and, most importantly, all the patients, families, and caregivers for their willingness to participate in this registry, which is sponsored by Novartis Gene Therapies, Inc.
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