Genethon, a global pioneer in gene therapy research and development for rare genetic diseases, has announced compelling long-term efficacy results from its micro-dystrophin gene therapy (GNT0004) for Duchenne muscular dystrophy (DMD). The data, presented at the 32nd Annual Congress of the European Society of Gene and Cell Therapy (ESGCT) held October 7–10, 2025, in Seville, Spain, revealed that three treated DMD patients maintained significant motor function improvements and experienced durable reductions in key biomarkers two years post-treatment.
Strong Two-Year Clinical Outcomes
The new data demonstrate that patients who received Genethon’s low-dose GNT0004 gene therapy showed sustained motor function gains and reduced muscle damage compared to untreated individuals. Over the two-year follow-up, participants experienced a meaningful increase in motor scores, substantial reductions in creatine phosphokinase (CPK)—a biomarker of muscle injury—and stabilization of disease progression on MRI imaging.
“These patients were treated in the dose-escalation portion of our Phase 1/2/3 European trial, and we are thrilled to share these positive long-term findings as our pivotal Phase 3 study moves forward,” said Frédéric Revah, Chief Executive Officer of Genethon. “Importantly, these results were achieved with a therapeutic dose of 3×10¹³ vg/kg, which is lower than other DMD gene therapies currently in development. This same dose is now being evaluated in our Phase 3 trial enrolling 64 ambulatory boys aged 6 to 10.”
Details from the Phase 1/2 Dose Escalation Trial
The Phase 1/2 study included five patients—two treated at an initial lower dose and three at the therapeutic dose of 3×10¹³ vg/kg. The results presented by Dr. Arnaud Valent, M.D., Genethon’s Head of Medical Activities and Pharmacovigilance, confirmed that the therapeutic dose achieved robust and durable efficacy with no serious adverse effects.
The findings indicate that the treatment is both effective and well tolerated, with clinical benefits maintained over two years, supported by multiple key parameters:
- Motor Function:
Patients treated with GNT0004 demonstrated a +5.8-point improvement on the North Star Ambulatory Assessment (NSAA) scale at 18 months compared to untreated matched controls from a parallel natural history study. This improvement is more than double the clinically meaningful threshold of 2.5 points, confirming a significant functional benefit that persisted at two years. - Functional Mobility:
Timed functional tests showed meaningful improvement, with treated patients performing the “rise from floor” test 6.98 seconds faster and exhibiting an increase in walking speed by +0.67 meters per second over 10 meters, compared to natural history controls. - Biomarker Response:
CPK levels—indicative of muscle breakdown—showed a 75% reduction at 18 months and remained 61% below baseline at two years, demonstrating long-term stabilization of muscle cell membranes and reduced ongoing damage. - MRI Imaging Results:
Quantitative MRI analysis revealed a 7% slower increase in muscle fat fraction compared to untreated patients, indicating that GNT0004 therapy successfully slowed disease progression at the tissue level. - Safety Profile:
No serious adverse events were reported during the two-year follow-up period. Patients received transient prophylactic immunosuppression, and the treatment maintained a favorable safety profile throughout.
Next Steps: Phase 3 Pivotal Trial Underway
Building on these encouraging results, Genethon has initiated its Phase 3 pivotal trial, now enrolling in France and soon expanding across 13 international sites. The study will evaluate the same 3×10¹³ vg/kg dose in 64 ambulatory boys aged 6–10 years with confirmed DMD, focusing on durability, safety, and long-term functional outcomes.
“Our goal is to provide a durable and transformative gene therapy option for boys living with Duchenne,” said Dr. Revah. “These results strengthen our confidence in GNT0004’s potential to deliver meaningful and lasting benefits at a lower dose than competing programs.”
A Step Forward for Duchenne Gene Therapy
Duchenne muscular dystrophy is a severe X-linked genetic disorder caused by mutations in the dystrophin gene, leading to progressive muscle degeneration and weakness. While several gene therapies are in development, many face challenges related to high vector doses and immune responses. Genethon’s GNT0004 distinguishes itself with its low-dose approach, potentially offering a safer, more sustainable treatment option that maintains efficacy while minimizing risk.
The positive two-year results presented at ESGCT 2025 reinforce Genethon’s scientific leadership and its mission to make gene therapy accessible and effective for rare disease patients worldwide.
“These findings represent a significant milestone not just for Genethon, but for the entire Duchenne community,” said Dr. Valent. “The combination of durable efficacy, improved safety, and lower dosing positions GNT0004 as a truly differentiated candidate in the evolving DMD gene therapy landscape.”
As Genethon continues its pivotal trial and collaborates with global partners, the company remains committed to advancing innovative genetic therapies that deliver real-world, long-term benefits to patients and families affected by rare neuromuscular diseases.
Summary:
Genethon’s low-dose micro-dystrophin gene therapy (GNT0004) demonstrated durable efficacy over two years in Duchenne muscular dystrophy patients, showing improved motor function, reduced CPK levels, and slowed disease progression. With no serious safety concerns and a lower therapeutic dose than competing therapies, GNT0004 is now progressing through a Phase 3 pivotal trial enrolling 64 boys across multiple global sites.
About Duchenne muscular dystrophy
Duchenne muscular dystrophy is a rare progressive genetic disease that affects all the muscles in the body and mainly boys (1 in 5,000). It is caused by abnormalities in the gene responsible for the production of dystrophin, a structural protein essential for the stability of muscle fiber membranes and their metabolism. The absence of dystrophin leads to progressive degeneration of the skeletal and cardiac muscles, loss of walking and respiratory abilities, cardiomyopathy, and death, usually between the ages of 20 and 40.
About GNT0004 and the trial
The gene therapy product GNT0004 consists of an AAV8 (adeno-associated virus) vector and the optimized hMD1 transgene, a shortened but functional version of the gene encoding dystrophin, the protein that is deficient in people with Duchenne muscular dystrophy. This vector is designed to express itself in muscle tissue and also in the heart, thanks to a Spc5-12 promoter sequence specific to these tissues. GNT0004 is administered by a single intravenous injection. It was developed by Genethon, in partnership with Prof. Dickson’s teams (University of London, Royal Holloway) and the Institut de Myologie (Paris).
