GNT0004 confirms its clinical efficacy with stabilization of motor functions in DMD patients for up to 2 years

Genethon has unveiled the 2-year follow-up data from its GNT0004  gene therapy clinical trial for Duchenne Muscular Dystrophy (GNT-016-MDYF) at the annual meeting of the American Society of Gene & Cell Therapy (ASGCT) in New Orleans, May 13 – 17, 2025. GNT0004 is an AAV8  vector containing a shortened but functional version of the gene encoding dystrophin, the protein deficient in people with DMD. Five patients, aged 6 to 10 years, were treated, 2 at the first dose level and 3 at the second dose level (3×10¹³ vg/kg). The initial part of the clinical trial aimed at selecting the optimal dose (dose escalation phase), evaluating the tolerance and preliminary efficacy of the treatment and determined the effective dose for the pivotal phase of the GNT-016-MDYF trial, which is expected to start in mid-2025 (3×10¹³ vg/kg).

Genethon CEO Frederic Revah observed, “The results of our gene therapy GNT0004 are very positive in patients treated at the dose of 3×10¹³ vg/kg, both in terms of microdystrophin expression and clinical efficacy criteria. Besides these results, the advantage of our product lies in the selected dose for the pivotal phase, which is lower than those used in other gene therapy trials for Duchenne Muscular Dystrophy. We are currently preparing the pivotal phase that we will conduct in Europe and the US.
Safety, efficacy, and pharmacodynamic results show good tolerance of GNT0004 associated with transient immunological prophylactic treatment, as well as efficacy data in terms of microdystrophin expression, CPK reduction, and clinical criteria (NSAA, timed tests). Patients treated at the effective dose show prolonged improvement or stabilization of motor functions and significant persistent reduction in creatine kinase (CPK) levels, a key marker of muscle damage.
One-year post-treatment, the comparison of the three patients treated at the effective dose with a group of 34 untreated patients, matched by age and followed in the same centers and by the same practitioners, shows a difference of +4.7 points in the score obtained using the internationally recognized clinical evaluation scale NSAA between treated and untreated patients.
At 24 months post-treatment, key observations include:
• For the 2 patients who reached 2 years post-treatment out of the 3 treated at the effective dose, the trial shows stabilization of motor functions measured by the NSAA scale , while untreated patients from the parallel natural history study showed a continuous and significant average decline in NSAA. For one treated patient, the observed improvement allowed reaching the maximum score of 34 at 12 months, confirmed at 24 months post-treatment.
• Stabilization of CPK reduction between 50% and 87% on average: >75% at 18 months post-treatment (data from the 3 patients treated at the effective dose), and persistent (up to 24 months follow-up for the first two patients treated at this dose).
• The reassuring safety profile of the gene therapy drug is confirmed two years after injection, without the occurrence of serious adverse effects at the selected dose, which is notably lower than that used for other gene therapy products under development for Duchenne Muscular Dystrophy.

21/05/2025