Long-term Safety of Onasemnogene Abeparvovec for Patients with Spinal Muscular Atrophy: Real-world Findings from the RESTORE Registry

Topic:

Clinical Trials

Poster Number: P280

Author(s):

Richard Finkel, MD, Center for Experimental Neurotherapeutics, St. Jude Children’s Research Hospital, Iulian Alecu, MD, Novartis Pharmaceuticals, Sandra Lopez-Leon, MD, PhD, Novartis Pharmaceuticals, Andreja Ilic, MA, Novartis Pharmaceuticals, Andreas Brueckner, MS, Novartis Pharmaceuticals, Kamal Benguerba, MD, MSc, Novartis Gene Therapies Switzerland GmbH, Sandra Reyna, MD, Novartis Gene Therapies, Inc., Omar Dabbous, MD, MPH, Novartis Gene Therapies, Inc., Nayla Mumneh, MD, Novartis Gene Therapies, Inc., Laurent Servais, MD, PhD, MDUK Oxford Neuromuscular Centre & NIHR Oxford Biomedical Research Centre, Oxford, UK

Background: Spinal muscular atrophy (SMA) is a genetic disorder causing progressive loss of motor neurons. Clinical trials have demonstrated safety and efficacy of onasemnogene abeparvovec (OA), a one-time survival motor neuron gene replacement therapy, in patients with SMA, though follow-up durations were limited.
Objective/Methods: RESTORE is a prospective, global, non-interventional, observational SMA patient registry initiated in 2018. Long-term OA safety was evaluated in RESTORE patients (included as of December 2023) with data collected from treatment initiation. Adverse events (AEs) and AEs of special interest (AESI) were analyzed based on MedDRA preferred and grouped terms, respectively. Cumulative incidence (first events) and interval prevalence (repeating events) of AESI were provided at 3, 6, 9, and 12 months, and then yearly (up to 5 years).
Results: 140 patients met the analysis criteria, with a median (minimum–maximum) time of observation after OA of 33.89 (0.4–55.4) months. The most common AEs were aspartate aminotransferase (AST) increased (n=41; 29%), pyrexia (n=38; 27%), alanine aminotransferase (ALT) increased (n=35; 25%), and vomiting (n=33; 24%). Serious AEs were reported in 58 patients (41%). The most common AESI were hepatotoxicity (n=60; 43%) (mainly isolated AST/ALT elevations), thrombocytopenia (n=30; 21%), and cardiac AEs (n=25; 18%) (mainly elevated troponin I), all without associated clinical signs or symptoms. Thrombotic microangiopathy was reported for three patients (2%). No dorsal root ganglia toxicity AEs were reported. One case of malignant neoplasm of spinal cord was reported and assessed as not related to OA [1]. Most AESI occurred within 3 months of treatment. There were no late-onset AESI over 5 years.
Conclusions: Long-term real-world safety RESTORE findings were consistent with the established safety profile for OA. Time-to-onset and interval prevalence analyses demonstrated that most AESI occurred within 3 months of OA infusion, and no long-term or late-onset toxicities were reported over a 5-year follow-up.

[1.]Retson L, et al. Mol Ther. 2023;31:2991-8.