Effectiveness and Safety of Onasemnogene Abeparvovec in Older Patients with Spinal Muscular Atrophy: Real-World Outcomes from the RESTORE Registry


Clinical Management

Poster Number: 79


Laurent Servais, MD, PhD, Department of Pediatrics, MDUK Oxford Neuromuscular Center, University of Oxford, Darryl De Vivo, MD, Columbia University Medical Center, Janbernd Kirschner, MD, Medical Center-University of Freiburg; University Hospital Bonn, Faculty of Medicine, Eugenio Mercuri, Paediatric Neurology and Centro Clinico Nemo, Catholic University and Policlinico Gemelli, Fondazion, Francesco Muntoni, MD, Great Ormond Street Institute of Child Health, London, UK, Eduardo Tizzano, Department of Clinical and Molecular Genetics, Hospital Valle Hebron, Susana Quijano-Roy, Garches Neuromuscular Reference Center, APHP Raymond Poincare University Hospital, Kayoko Saito, MD, PhD, Institute of Medical Genetics, Tokyo Women’s Medical University, Melissa Menier, Atlas Clarity LLC, Nicole LaMarca, DNP, MSN, CPNP, PMHS, Novartis Gene Therapies, Frederick A. Anderson, Center for Outcomes Research, University of Massachusetts Medical School, Omar Dabbous, Novartis Gene Therapies, Richard Finkel, MD, St. Jude Children’s Research Hospital, Memphis, TN, USA.

Objective: We aimed to describe real-world outcomes in patients with spinal muscular atrophy (SMA) aged ?6 months at the time of onasemnogene abeparvovec (OA) infusion.
Background: Interventional trials of OA demonstrated safety and efficacy in patients <6 months of age.
Methods: We evaluated patients aged ?6 months receiving OA (regardless of treatment with other disease-modifying treatments) in RESTORE (a comprehensive, prospective, multicenter, multinational, observational registry of patients with SMA).
Results: As of May 23, 2021, RESTORE included 117 patients with SMA aged ?6 months at OA infusion (51 [43.6%] were ?6–<12 months; 57 [48.7%] were ?12–<24 months; and 9 [7.7%] were ?24 months). The majority of patients (n=73/117; 62.4%) had two copies of the SMN2 gene. Thirty-eight (32.5%) participants received OA monotherapy; 26 (22.2%) were administered OA that was preceded and followed by nusinersen and/or risdiplam; and 53 (45.3%) switched from nusinersen to OA. Of 81 patients with information available, 41 (50.6%) weighed ?8.5 kg at OA infusion. At that time, the majority of patients (n=76/114; 66.7%) were diagnosed with SMA type 1 and 7/114 (6.1%) were presymptomatic. Of 28 patients with ?2 evaluable CHOP INTEND assessments, 25 (89.3%) increased or maintained score, and 18 (64.3%) achieved ?4-point increases (11 patients aged ?6–<12 months; 7 patients aged ?12–<24 months). Adverse event (AE) data were reported for 116 patients; 71 (61.2%) reported at least one treatment-emergent AE and 33 (28.4%) reported at least one serious AE (20 [17.2%] related to OA treatment).
Conclusions: Patients with SMA aged ?6 months at OA infusion benefited from treatment as measured by CHOP INTEND scores. The safety profile of OA in patients aged ?6 months at infusion is consistent with the overall AE profile for OA, with no apparent pattern of AE incidence or severity according to age at infusion.