Gene Therapy: Two-Year Consolidated Results from Genethon’s Clinical Trial for Duchenne Muscular Dystrophy
Presented on May 17 at the 2025 Annual Meeting of the American Society of Gene & Cell Therapy (ASGCT), the results of Genethon’s trial for Duchenne Muscular Dystrophy show stabilization of motor functions and a significant, sustained reduction in CPK levels in patients treated at the effective dose. The pivotal phase is scheduled to begin mid-2025 in Europe and the United States.
Positive clinical outcomes up to 2 years
At the annual meeting of the American Society of Gene & Cell Therapy (ASGCT) in New Orleans, Genethon presented the two-year follow-up data from its GNT0004 gene therapy clinical trial for Duchenne Muscular Dystrophy. Five boys aged 6 to 10 years were treated: two at the first dose level and three at the second dose level (3x10¹³ vg/kg).
The initial phase of the trial, designed to identify the optimal dose and assess safety and preliminary efficacy, confirmed 3x10¹³ vg/kg as the effective dose for the upcoming pivotal phase, scheduled for mid-2025.
Maintenance of motor functions and CPK level reduction
The safety, efficacy, and pharmacodynamic data show good tolerance of GNT0004 when administered with transient immunological prophylaxis. Efficacy outcomes were demonstrated through microdystrophin expression, a sustained reduction in creatine kinase (CPK) levels—a key marker of muscle damage—and clinical criteria (NSAA, timed tests).
In patients treated at the effective dose, prolonged improvement or stabilization of motor functions was observed, along with a significant and persistent reduction in CPK levels.
At one year post-treatment, a comparison between the three treated patients and a group of 34 untreated, age-matched patients followed in the same centers showed a +4.7 point difference in the NSAA score, a recognized international clinical evaluation scale.
Results at 24 months post-treatment
Among the two patients who reached the 24-month follow-up after treatment at the effective dose, the trial demonstrated stabilization of motor functions measured by NSAA, in contrast to the continuous decline observed in the untreated group.
For one of them, improvement led to a maximum NSAA score of 34 at 12 months, which was maintained at 24 months.
The reduction in CPK levels ranged from 50% to 87%, with an average drop of over 75% at 18 months post-treatment. This reduction persisted up to 24 months in the first two patients treated at the effective dose.
Confirmed safety profile
The safety profile of GNT0004 was confirmed two years post-injection, with no serious adverse events reported at the selected dose. Notably, this dose is lower than those used in other gene therapy trials for Duchenne Muscular Dystrophy.
“The results of our GNT0004 gene therapy are very positive in patients treated at the 3x10¹³ vg/kg dose, both in terms of microdystrophin expression and clinical efficacy criteria. Beyond these results, our product’s strength lies in the selected dose for the pivotal phase, which is lower than that used in other gene therapy trials for Duchenne Muscular Dystrophy. We are currently preparing the pivotal phase, which we will conduct in Europe and the US,” said Frédéric Revah, CEO of Genethon.
A vector targeting muscle and cardiac tissue
GNT0004 is composed of an AAV8 vector and the optimized hMD1 transgene, a shortened but functional version of the gene encoding dystrophin. The vector is designed for expression in skeletal muscle and heart tissue, thanks to a specific Spc5-12 promoter sequence. GNT0004 is administered via a single intravenous injection.
Developed by Genethon, in collaboration with Professor Dickson’s team (University of London, Royal Holloway) and the Institute of Myology (Paris), the trial combines Phases 1/2/3. It is being conducted in France and the United Kingdom in ambulatory boys aged 6 to 10 years with Duchenne Muscular Dystrophy.