Safety and Efficacy of Vesemnogene Lantuparvovec, an AAV-Based Gene Therapy in Young Children Under 24 Months with Spinal Muscular Atrophy in Low- and-Middle- Income Countries. Second Interim Report (August 2025).

IntroductionSpinal muscular atrophy (SMA) is a monogenic neuromuscular disorder due to the survival motor neuron 1 mutation. Onasemnogene abeparvovec is a U.S. FDA approved single-dose gene therapy for SMA, but it is priced at USD 2.13 million per patient which severely limits its accessibility in low- and middle-income countries (LMICs). We conducted a phase 1 trial on vesemnogene lantuparvovec, an affordably priced substitute to onasemnogene abeparvovec intended for use in LMICs. MethodsSixteen patients with SMA (eight each with type 1 and type 2) received a single dose of intrathecal vesemnogene lantuparvovec. Eleven patients received a low dose (1.5 x 1014 vg) and five received high dose (3.0 x 1014 vg). The primary outcomes were safety, and efficacy with the change from baseline in the developmental gross motor milestones achieved according to World Health Organization (WHO) criteria. Overall survival was primarily evaluated in type 1 SMA patients. This trial was registered with ClinicalTrials.gov NCT06288230. ResultsAs of the data cutoff in August 2025, 16 patients enrolled have been followed-up to at least 3-month post-treatment. The median age at diagnosis and dosing were 4.4 months (0.0, 18.0) and 10.7 months (2.8, 22.5), respectively. The most common adverse event (AE) was transiently increased aspartate aminotransaminase which occurred in 11 patients (69%), with one patient having a level twice the upper limit of normal. No patient required prolonged prednisolone prophylaxis. The most serious AEs were respiratory tract infections which occurred in four (50%) of eight patients with type 1 SMA, leading to invasive ventilation in two and one of them eventually died. Among the eight patients with type 1 SMA, one had gained one new WHO milestone at 3- month post-treatment. Among the eight patients with type 2 SMA, at 3-month post treatment, three patients had gained at least one new WHO milestone while one had gained three new milestones and could crawl. ConclusionsIn patients with type 1 and type 2 SMA below 24 months, a single intrathecal dose of vesemnogene lantuparvovec was safe and well-tolerated, resulting in improved developmental gross motor milestones, which contrast with patients referred to the trial but were untreated. Further studies are necessary to confirm this gene therapys long term safety and efficacy.