Onasemnogene abeparvovec gene therapy for spinal muscular atrophy type 1: phase 3 study (str1ve-us)

Introduction and Objective Onasemnogene abeparvovec (formerly AVXS-101), is designed to address the genetic root cause of spinal muscular atrophy (SMA), survival motor neuron 1 gene (SMN1) deletion/mutation. Here, we evaluate final data from STR1VE-US (NCT03306277), a multicenter, open-label, single-arm, single-dose, Phase 3 study conducted in the United States, investigating efficacy and safety of one-time intravenous infusion of onasemnogene abeparvovec in patients with SMA1 (aged, Methods Co-primary endpoints: independent sitting for ≥30 seconds at the 18 months visit, survival (no death/permanent ventilation) at 14 months of age. Co-secondary endpoints: ability to thrive at 18 months (composite of: tolerates thin liquids, no mechanical nutrition support, maintains weight consistent with age), independence from ventilatory support at 18 months (based on Trilogy BiPAP usage). Safety endpoints: unanticipated treatment-related toxicity of Grade ≥3 based on CTCAE. Results All co-primary and co-secondary endpoints demonstrated statistically significant benefits of onasemnogene abeparvovec compared with untreated controls in the Pediatric Neuromuscular Clinical Research (PNCR) study. Thirteen of 22 (59.1%) patients treated with onasemnogene abeparvovec achieved the milestone of functional independent sitting for ≥30 seconds at the 18-month visit (P Conclusions In the STR1VE-US study, patients with SMA1 treated with onasemnogene abeparvovec demonstrated a significant therapeutic benefit and a favourable the benefit-risk profile.