Safety and tolerability of onasemnogene abeparvovec for patients with spinal muscular atrophy weighing ≤17 kg and ≤24 months old from OFELIA, a phase 4, open-label, multicenter, non-randomised, interventional study.

Background: OFELIA aimed to evaluate outcomes related to safety and motor milestones following administration of onasemnogene abeparvovec, a one-time gene replacement therapy, for patients with spinal muscular atrophy (SMA) from Latin America. Methods: OFELIA (NCT05073133) is a phase 4, 18-month, open-label, multicenter, non-randomised study (Brazil, Argentina) of onasemnogene abeparvovec treatment (1·1 × 10 Findings: Sixteen patients were enrolled (n = 11/16 female; n = 10/16 SMA type 1) (n = 17 screened). All reported adverse events (AEs). Eleven reported serious AEs; 12 reported an AE of special interest, most commonly hepatotoxicity (asymptomatic) (n = 11/12), thrombocytopenia (n = 5/12), and thrombotic microangiopathy (n = 2/12). Two deaths occurred: one possibly related to treatment (AST >20 × upper limit of normal, sepsis, infection, multiorgan failure, thrombotic microangiopathy) and one due to respiratory infection. Most patients maintained/improved motor milestones up to 18 months post-onasemnogene abeparvovec (e.g., sitting, crawling, standing, walking), including those in the >12-24-month age group. Interpretation: Most common AEs of special interest were hepatotoxicity, thrombocytopenia, and thrombotic microangiopathy; incidence rates (hepatotoxicity, thrombocytopenia) were similar compared with studies in patients >6 months of age and >8·5 kg. Efficacy data on demonstration of motor milestones suggest that Latin American patients with SMA may benefit from onasemnogene abeparvovec treatment. Funding: The study was funded by Novartis Pharma AG, Basel, Switzerland.