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)

Introduction

Spinal muscular atrophy (SMA) is a monogenic neuromuscular disorder due to survival motor neuron 1 mutation. Onasemnogene abeparvovec is a 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-and-middle-income countries (LMIC). We conducted a Phase 1 trial on vesemnogene lantuparvovec, an affordably priced substitute to onasemnogene intended for use in LMICs.

Methods

Sixteen patients with SMA (eight SMA Type 1 and Type 2 each) received a single dose of intrathecal vesemnogene lantuparvovec. Eleven patients received a low dose (1.5 × 10 ¹⁴ vg) and five received high dose (3.0 × 10 ¹⁴ 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.

Results

As of the data cutoff in August 2025, 16 patients enrolled have been followed-up to at least three-month post-treatment. The median ages at diagnosis and dosing were 5 months (0.1, 18) and 12 months (3, 22), respectively. The commonest adverse event (AE) was transiently increased aspartate amino-transaminase which occurred in 11 patients (69%), with one patient having a level twice the upper limit of normal. No patient had 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 2 and one of them eventually died.

Among the eight patients with SMA Type 1, two had gained one WHO milestone at 3-month post-treatment. Among the eight 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 could walk with assistance.

Conclusions

In 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 therapy’s long term safety and efficacy. ( ClinicalTrials.gov number NCT06288230 .)