Abstract
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(14) vg/kg) for symptomatic patients with SMA ≤24 months of age and ≤17 kg (grouped by age [0-12 vs >12-24 months] and weight [<8·5 kg vs ≥8·5 kg]). The primary endpoint was safety. The secondary endpoint was demonstration of motor milestones measured at screening and at 6, 12, and 18 months post-onasemnogene abeparvovec infusion, according to the World Health Organization Multicentre Growth Reference Study criteria. 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.