Safety and Efficacy of IV Onasemnogene Abeparvovec for Pediatric Patients With Spinal Muscular Atrophy
Hugh J. McMillan, Giovanni Baranello, Michelle A. Farrar, Craig M. Zaidman, T. Moreno, Liesbeth De Waele, Yuh‐Jyh Jong, Vincent Laugel, Susana Quijano‐Roy, Eugenio Mercuri, Yin‐Hsiu Chien, Volker Straub, Basil T. Darras, Julia Seibert, Roberto Bernardo Escudero, I. Alecu, F. Freischläger, Francesco Muntoni, for the SMART Study Group
Abstract
BACKGROUND AND OBJECTIVES: Safety and efficacy of IV onasemnogene abeparvovec has been demonstrated for patients with spinal muscular atrophy (SMA) weighing <8.5 kg. SMART was the first clinical trial to evaluate onasemnogene abeparvovec for participants weighing 8.5-21 kg. METHODS: SMART was an open-label, multicenter, phase 3b study conducted across 13 sites in 9 countries (NCT04851873). Symptomatic pediatric participants with SMA (any type; treatment-naïve or had discontinued prior treatment) were stratified into 3 weight cohorts (≥8.5-13, >13-17, and >17-21 kg), administered onasemnogene abeparvovec, and followed for 52 weeks. Corticosteroids were initiated 24 hours before infusion with dose increases in response to adverse events (AEs) and subsequent tapering at investigator discretion. The primary objective was safety. Secondary objective was efficacy (motor function/motor milestones). RESULTS: copies) achieved new motor milestones. DISCUSSION: Onasemnogene abeparvovec safety profile was similar across weight groups in this heterogenous participant population. Frequency and duration of asymptomatic aminotransferase elevations and thrombocytopenia are notable findings. Most participants demonstrated maintenance or improvement of motor function, suggesting clinical benefit for patients with SMA weighing up to 21 kg. TRIAL REGISTRATION INFORMATION: ClinicalTrials.gov identifier (NCT04851873, clinicaltrials.gov/study/NCT04851873) submitted April 19, 2021. First participant enrolled on September 8, 2021. CLASSIFICATION OF EVIDENCE: This study provides Class IV evidence that intravenous onasemnogene abeparvovec is safe in pediatric patients with SMA who weigh 8.5-21 kg.