Genethon Presents Positive Initial Results from a Phase 1/2/3 Trial of its Gene Therapy (GNT0004) for Duchenne Muscular Dystrophy at ASGCT Breakthroughs in Muscular Dystrophy in Chicago

PARIS, FRANCE (November 19, 2024) – Genethon, a pioneering gene therapy research organization created by AFM-Telethon, today presented positive results from the Phase 1/2 dose escalation part of an international multicenter all-in-one Phase 1/2/3 trial evaluating its gene therapy, GNT-0004, for Duchenne muscular dystrophy (DMD) at the ASGCT Breakthroughs in Muscular Dystrophy conference, Nov. 19 – 20, 2024, in Chicago, IL. Based on these results, Genethon expects to launch pivotal trial in Europe in Q2/2025 and in the US.

• Based on positive safety and efficacy data in the Phase 1/2 dose escalation phase of the all-in-one study, Genethon expects to launch pivotal trials in Europe in 2025 and the US.
• The results showed that one to two years after treatment at the higher of two doses of GNT0004, patients experienced stabilization in the North Star Ambulatory Assessment measuring motor functions compared with a decline in untreated patients in the parallel disease natural history study. 
See the video of one patient’s remarkable improvement (https://youtu.be/LSeJzj-vUKk)

Frederic Revah, Genethon’s Chief Executive Officer, observed, “The results of treatment with our GNT0004 gene therapy are very positive in patients treated at the higher of two doses, both in terms of micro-dystrophin expression and clinical improvement. In addition, the strength of our product lies in this selected dose, which is lower than those used in other gene therapy trials for DMD. GNT0004 has the potential to be the best-in-class curative gene therapy for DMD.”

Dr. Revah emphasized, “These clinical results demonstrate that gene therapy can provide solutions to one of the most complex genetic diseases. Our aim is to start the confirmatory (pivotal) phase in more than 60 children in Europe in the second quarter of 2025, followed by the US.”

The presentation, titled “GNT0004, Genethon’s AAV8 Vector-delivered Microdystrophin Gene Therapy for Duchenne Muscular Dystrophy: First Data from Phase 1/2 Part of GNT-016-MDYF All-in-one Clinical Trial in Ambulant Boys,” was made by Serge Braun, PhD,  Genethon’s Director of Neuromuscular Strategy.

The Phase1/2 part of the all-in-one study, designed to assess tolerance and initial evidence of efficacy, was completed at the end of October and determined the therapeutic dose of GNT0004 to be used in the pivotal study. Five patients, between ages 6 and 10, were treated at one of two doses; two at the first level and three at a higher level.

The safety and pharmacodynamic data showed good tolerance of GNT0004 combined with transient immunological prophylaxis, as well as efficacy data, both in terms of micro-dystrophin expression and functional improvement.The findings in patients receiving the second dose level (3×10¹³ vg/kg) showed:

• Eight weeks after injection, up to 85% of muscle fibers expressed micro-dystrophin(mean 54%; 15%-85%) as measured by immunohistochemistry, and reconstitution of the dystrophin-associated protein complex. This expression coincides with a significant number of vector genome copies/muscle fiber nuclei, up to 2.4 (mean 1.2; 0.4-2.4).
• A fall in creatine phosphokinase (CPK) levels (a biomarker of muscular suffering) of between 50% and 87% (mean: 74%) 12 weeks after treatment, and persistent (up to 18 months of follow-up for the first two patients treated at this dose).

For all patients treated at the effective dose, the results also demonstrated, one to two years after treatment, stabilization of motor functions measured by a 34-point clinical evaluation scale. For one patient, an improvement was observed, reaching the maximum score of 34 at 12 months, and confirmed at 18 months post-treatment.

This development was remarkable compared with that of untreated patients in Genethon’s parallel natural history study, for whom motor function declined rapidly over the same period. After review and advice from the independent monitoring committee, these conclusive results enable Genethon to launch the confirmatory part of the trial (pivotal phase) with the inclusion of the first patients in mid-2025.