Genethon Reports Positive 2-Year Outcomes for AAV8 Gene Therapy Trial in Duchenne Muscular Dystrophy

Paris, France (May 17, 2025) – Genethon has released 2-year follow-up data from its GNT0004 (GNT-016-MDYF) clinical trial for Duchenne Muscular Dystrophy (DMD), which utilizes an AAV8 vector to deliver a functional dystrophin gene. The study, involving five patients aged 6 to 10, identified 3×10¹³ vg/kg as the effective dose for the upcoming pivotal phase, notably lower than doses in other DMD gene therapy trials.

Genethon CEO Frederic Revah highlighted the “very positive” results at the selected dose, showing both microdystrophin expression and clinical benefits. He emphasized the lower dose as an advantage as they prepare for pivotal trials in Europe and the US.

The AAV8 gene therapy demonstrated good tolerance with prophylactic immune treatment, alongside efficacy shown by microdystrophin expression, reduced CPK levels (a muscle damage marker), and positive clinical criteria (NSAA). Patients at the effective dose experienced sustained improvement or stabilization of motor functions and a significant, lasting reduction in CPK.

One year post-treatment, these patients showed a +4.7 point difference in NSAA score compared to a matched untreated group. At 24 months, the two patients reaching this milestone exhibited stabilized motor functions, contrasting with the continuous decline in untreated patients. One treated patient achieved and maintained the maximum NSAA score. CPK reduction remained stable (50-87% average, >75% at 18 months) and persistent for up to 24 months. The AAV8 gene therapy also maintained a reassuring safety profile at the lower selected dose, with no serious adverse effects reported after two years.

GNT0004 uses an AAV8 vector carrying the optimized hMD1 transgene, designed for expression in muscle and heart tissue via a specific promoter. It’s administered as a single intravenous injection and was developed by Genethon and academic partners. The ongoing trial combines dose escalation and a pivotal phase in France and the UK, for boys aged 6 to 10 with DMD who can still walk.