Genethon Shares Positive Phase 1/2/3 Results of GNT0004 for DMD at ASGCT Chicago

PARIS, France I November 19, 2024 I Genethon, an innovative gene therapy research institution established by AFM-Telethon, today announced encouraging outcomes from the Phase 1/2 dose escalation section of an international multicenter trial evaluating its gene therapy, GNT0004, aimed at treating Duchenne muscular dystrophy (DMD). These findings were presented at the ASGCT Breakthroughs in Muscular Dystrophy conference held on November 19 – 20, 2024, in Chicago, IL. Following these positive results, Genethon plans to initiate a pivotal trial in Europe by the second quarter of 2025 and shortly thereafter in the US.

Frederic Revah, the Chief Executive Officer of Genethon, remarked, "The therapeutic results of our GNT0004 gene therapy are immensely promising for patients treated with the higher of two dose levels, both in terms of micro-dystrophin production and clinical outcomes. Furthermore, the efficacy of our product at a comparatively lower dose than those used in other DMD gene therapy trials underscores its potential as a leading curative gene therapy for DMD."

Dr. Revah went on to say, "These clinical outcomes highlight the capability of gene therapy to address one of the most challenging genetic disorders. Our objective is to commence the confirmatory (pivotal) phase with over 60 children in Europe by the second quarter of 2025, followed by trials in 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 delivered by Serge Braun, PhD, Genethon’s Director of Neuromuscular Strategy.

The Phase 1/2 segment of the comprehensive study, designed to evaluate tolerance and initial efficacy evidence, concluded at the end of October. This phase established the therapeutic dose of GNT0004 for the pivotal study. Five patients, aged between 6 and 10, were treated at one of two doses; two at the initial dose level and three at a higher dose level.

Safety and pharmacodynamic data demonstrated good tolerance for GNT0004 combined with transient immunological prophylaxis, along with efficacy data in terms of micro-dystrophin expression and functional improvement. Patients treated at the second dose level (3×10^13 vg/kg) exhibited:

For all patients treated at the effective dose, results showed stabilization of motor functions, as measured by a 34-point clinical evaluation scale, one to two years after treatment. One patient showed an improvement, achieving the maximum score of 34 at 12 months, which was sustained at 18 months post-treatment.

Remarkably, this improvement was significant compared to untreated patients in Genethon’s parallel natural history study, where the mean motor function declined rapidly over the same period. Following a review and advice from the independent monitoring committee, these conclusive results enable Genethon to proceed with the pivotal phase of the trial, aiming to include the first patients by mid-2025.

About GNT0004 and the trial
The GNT0004 gene therapy is composed of an AAV8 (adeno-associated virus) vector and the optimized hMD1 transgene, a shortened but functional version of the gene encoding dystrophin, the protein deficient in individuals with DMD. This vector is intended to be expressed in muscle tissue and the heart, thanks to a tissue-specific Spc5-12 promoter sequence. Administered via a single intravenous injection, GNT0004 was developed by Genethon in collaboration with the teams of Prof. Dickson (University of London, Royal Holloway) and the Institut de Myologie (Paris). The trial, sponsored by Genethon, integrates Phases 1/2/3, starting with a dose-escalation phase followed by a pivotal phase at the finalized dose. It is being conducted in France and the UK, involving boys aged 6 to 10 with DMD who can still walk.

About Duchenne muscular dystrophy
DMD is a rare, progressive genetic disorder affecting all the body’s muscles, predominantly in boys (1 in 5000). It results from abnormalities in the gene responsible for producing dystrophin, a structural protein crucial for the stability of muscle fiber membranes and their metabolism. The lack of dystrophin leads to the progressive degeneration of skeletal and cardiac muscles, loss of walking ability and respiratory capacity, cardiomyopathy, and premature death between the ages of 20 and 40.

About Genethon
Genethon is a non-profit organization and a pioneer in the discovery and development of gene therapies for rare diseases, created by the AFM-Téléthon. The first gene therapy for spinal muscular atrophy, utilizing technologies developed at Genethon, is available globally. With over 200 scientists and professionals, Genethon is dedicated to developing innovative therapies that transform the lives of patients with rare genetic diseases. Thirteen products from Genethon’s R&D or collaborations are in clinical trials for diseases affecting the liver, blood, immune system, muscles, and eyes, with seven more potentially entering clinical trials in the next five years.