Twelve-Month Outcomes of Intrathecal Vesemnogene Lantuparvovec for Spinal Muscular Atrophy in Children Younger than 24 Months in Low- and Middle- Income Countries

Introduction Spinal muscular atrophy (SMA) is a monogenic neuromuscular disease caused by mutations in the survival motor neuron 1 (SMN1) gene. Onasemnogene abeparvovec is a U.S. FDA-approved single-dose gene therapy for SMA. Both its intravenous formulation (Zolgensma, approximately USD 2.13 million per patient) and intrathecal formulation (Itvisma, around USD 2.59 million per patient) are prohibitively expensive, substantially limiting accessibility in low- and middle-income countries (LMICs). We conducted a clinical study of vesemnogene lantuparvovec, an alternative to onasemnogene abeparvovec developed for use in LMIC settings. Methods Sixteen patients with SMA, including 8 with type 1 SMA and 8 with type 2 SMA, received a single intrathecal administration of vesemnogene lantuparvovec. Eleven patients were treated with a low dose (1.5 * 10^14 vg) and five with a high dose (3.0 * 10^14 vg). The primary endpoints were safety and efficacy, assessed by changes from baseline in developmental gross motor milestones according to the World Health Organization criteria. Overall survival was primarily evaluated in type 1 SMA patients. This trial was registered with ClinicalTrials.gov NCT06288230. Results As of the March 2026 cutoff date, 15 of 16 treated patients had completed at least 12 months of follow-up after treatment, while the remaining one type 1 SMA patient died of disease progression at month 6 post-treatment. At 12 months post-treatment, among the surviving 7 patient with type 1 SMA, the median age was 21.6 months (range, 16.1 to 32.3 months). Among the 16 treated patients, the median age at diagnosis was 4.4 months (range, 0.0 to 18.0 months), and the median age at dosing was 10.7 months (range, 2.8 to 22.5 months). All patients experienced at least one AE. Thirty-one AESIs were reported in 13 patients, including hepatotoxicity, thrombocypenia-related events and cardiac events. No patient required prolonged prednisolone prophylaxis. SAEs, including pneumonia, lower respiratory tract infection, upper respiratory tract infection, and haemorrhagic diarrhoea, occurred in 5 of 8 (63%) patients with type 1 SMA and 2 of 8 (25%) patients with type 2 SMA. Two patients with type 1 SMA required invasive ventilation, and one of whom subsequently died. At 12 months post-treatment, 11 of 16 treated patients (69%) gained at least one new WHO motor milestone versus baseline, including 3 type 1 and 8 type 2 SMA patients; one type 2 patient gained six WHO motor milestones and achieved independent walking. Conclusions In patients younger than 24 months of age with type 1 or type 2 SMA, a single intrathecal dose of vesemnogene lantuparvovec was safe and generally well tolerated and was associated with improvements in developmental gross motor milestones compared with outcomes observed among referred but untreated patients. Additional studies are required to further evaluate the long-term safety and efficacy of this gene therapy.