Onasemnogene abeparvovec for presymptomatic infants with two copies of SMN2 at risk for spinal muscular atrophy type 1: the Phase III SPR1NT trial

TLDR

SMA type 1 is a severe neuromuscular disease caused by SMN1 mutations that can be prevented with early gene therapy. The study aimed to evaluate the efficacy and safety of onasemnogene abeparvovec in presymptomatic infants with biallelic SMN1 mutations treated at ≤6 weeks of life. Efficacy was assessed by comparing 14 treated infants to a matched natural‑history cohort of 23 children in a Phase III, multicenter, single‑arm trial. All 14 infants independently sat, survived without ventilation, maintained weight, required no nutritional or respiratory support, and had no treatment‑related serious adverse events, demonstrating the therapy’s efficacy and safety and underscoring the need for universal newborn screening.

Abstract

Abstract SPR1NT ( NCT03505099 ) was a Phase III, multicenter, single-arm study to investigate the efficacy and safety of onasemnogene abeparvovec for presymptomatic children with biallelic SMN1 mutations treated at ≤6 weeks of life. Here, we report final results for 14 children with two copies of SMN2 , expected to develop spinal muscular atrophy (SMA) type 1. Efficacy was compared with a matched Pediatric Neuromuscular Clinical Research natural-history cohort ( n = 23). All 14 enrolled infants sat independently for ≥30 seconds at any visit ≤18 months (Bayley-III item #26; P < 0.001; 11 within the normal developmental window). All survived without permanent ventilation at 14 months as per protocol; 13 maintained body weight (≥3rd WHO percentile) through 18 months. No child used nutritional or respiratory support. No serious adverse events were considered related to treatment by the investigator. Onasemnogene abeparvovec was effective and well-tolerated for children expected to develop SMA type 1, highlighting the urgency for universal newborn screening.