Onasemnogene Abeparvovec Therapy Following Nusinersen Treatment in Eight Patients with Spinal Muscular Atrophy Type 1

Introduction: Innovative gene-modifying therapy can improve motor achievements of patients with spinal muscular atrophy (SMA). Onasemnogene abeparvovec (OAV101) is an adeno-associated viral vector gene therapy that introduces a functional copy of the SMN1 gene, which produces SMA protein that is essential for normal motor neuron function. Aim: To report our single-center clinical experience using OAV101 in patients with SMA Type 1 previously treated with nusinersen. Methods: Between October 2019 and September 2020, eight patients (aged 3-23 months) with SMA Type 1 were administered a single intravenous infusion of OAV101, individualized according to bodyweight (1.1 x 1014 vg/kg), and prophylactic immunosuppression. Change in motor function achievements was assessed using Children’s Hospital of Philadelphia Infant Test of Neuromuscular Disorders (CHOP INTEND) scores. Laboratory parameters, including liver enzymes and troponin were monitored. Results: OAV101 improved motor function in all eight patients. The average increase in CHOP INTEND scores were 11.14 points (range 3-21 points) 10 weeks after OAV101, with the highest score of 21 points in a child aged 13 weeks. The weekly increase in CHOP INTEND score following OAV101 was 1.11 points, 2.5-fold higher than that achieved with prior nusinersen treatment (0.42 points) (p=0.69; paired t-probe). Any increase in laboratory parameters occurred early after OAV101 and typically resolved to normal levels. Noninvasive ventilation use was decreased in two patients. Conclusion: OAV101 improved motor function in patients with SMA aged 3 23 months, with a manageable safety profile. Our report contributes real-world evidence of OAV101 treatment for SMA.