Safety and Efficacy of Vesemnogene lantuparvovec, an AAV-based Gene therapy for Spinal Muscular Atrophy in Children Less Than 24 Months of Age in Low-Middle Income Countries. First interim report as of April 2025
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Introduction
Spinal muscular atrophy (SMA) is a monogenic neuromuscular disorder due to mutation of the survival motor neuron 1. Onasemnogene abeparvovec is an US FDA approved single- dose gene therapy for SMA, but is priced at USD 2.1 million per patient which severely limit its accessibility in low-middle-income countries (LMIC). We conducted a Phase 1 trial on Vesemnogene lantuparvovec, a low-cost substitute to onasemnogene intended for use in LMICs.
Methods
Sixteen patients with SMA (8 SMA Type 1 and 8 SMA Type 2) received a single dose of intrathecal Vesemnogene lantuparvovec. Eleven of the patients received a low dose (1.5 × 10 14 vg) and 5 received high dose (3.0 × 10 14 vg). The primary outcome was safety, and efficacy outcome was the change from baseline in the developmental gross motor milestones achieved according to WHO criteria.
Results
As of the data cutoff on April 15 2025, 16 patients enrolled have been followed-up to at least 1-month post treatment. The most common adverse event (AE) was transient increased transaminase which occurred in 12 patients (75%), only one patient had level twice upper limit of normal, no patient had required prolonged prednisolone prophylaxis. The most serious AEs were respiratory tract infections which occurred in 4 (50%) of 8 patients with Type 1 SMA, which had led to invasive ventilation in 2 and one of whom eventually died. Among the 8 patients with SMA Type 1, only 2 had gained one WHO milestone at 1-month and 3-month post treatment. Among the 8 patients with SMA Type 2, at 3-month post treatment, all patients had gained at least one WHO milestone while 2 had gained four milestones and were able to walk with assistance.
Conclusions
In patients with Type 1 and Type 2 SMA aged below 24 months, a single intrathecal dose of Vesemnogene lantuparvovec was safe and well-tolerated, and resulted in improved developmental gross motor milestones that contrast with patients referred to the trial but were untreated. Further studies are necessary to confirm the safety and efficacy of this gene therapy. ( ClinicalTrials.gov number NCT06288230 .)
