GNT 0004 / Genethon, Sarepta Therapeutics - LARVOL DELTA

Sustained functional, biomarker, and MRI therapeutic effects following GNT0004 gene therapy in ambulant boys with Duchenne muscular dystrophy: Long-term Phase 1/2 results from the GNT-016-MDYF trial (ESGCT 2026) - No abstract available

Biomarker • Gene therapy • P1/2 data • Duchenne Muscular Dystrophy • Gene Therapies • Genetic Disorders • Muscular Dystrophy

Encouraging hepatic safety profile of Genethon's AAV8 microdystrophin gene therapy (GNT0004): cumulative clinical experience from an ongoing clinical trial in ambulant DMD boys (ESGCT 2026) - No abstract available

Clinical • Gene therapy • Duchenne Muscular Dystrophy • Gene Therapies

GNT-016-MDYF: A clinical study in 3 parts with a microdystrophin (called GNT0004), a new gene therapy in boys with Duchenne disease who can still walk. The study will start with finding the proper treatment dose (part 1). After that, a comparative study versus placebo will start to assess the safety and the effectiveness of the proper dose of this therapy (part 2). In the end, a follow up... (clinicaltrialsregister.eu) - P1/2 | N=42 | Recruiting | Sponsor: Genethon | N=62 ➔ 42

Enrollment change • Duchenne Muscular Dystrophy • Gene Therapies • Genetic Disorders • Muscular Dystrophy

GNT-016-MDYF: A clinical study in 3 parts with a microdystrophin (called GNT0004), a new gene therapy in boys with Duchenne disease who can still walk. The study will start with finding the proper treatment dose (part 1). After that, a comparative study versus placebo will start to assess the safety and the effectiveness of the proper dose of this therapy (part 2). In the end, a follow up... (clinicaltrialsregister.eu) - P1/2 | N=42 | Recruiting | Sponsor: Genethon

New P1/2 trial • Duchenne Muscular Dystrophy • Gene Therapies • Genetic Disorders • Muscular Dystrophy

GNT-016-MDYF: A clinical study in 3 parts with a microdystrophin (called GNT0004), a new gene therapy in boys with Duchenne disease who can still walk. The study will start with finding the proper treatment dose (part 1). After that, a comparative study versus placebo will start to assess the safety and the effectiveness of the proper dose of this therapy (part 2). In the end, a follow up... (clinicaltrialsregister.eu) - P1/2 | N=61 | Recruiting | Sponsor: Genethon | N=40 ➔ 61

Enrollment change • Duchenne Muscular Dystrophy • Gene Therapies • Genetic Disorders • Muscular Dystrophy

GNT-016-MDYF: A clinical study in 3 parts with a microdystrophin (called GNT0004), a new gene therapy in boys with Duchenne disease who can still walk. The study will start with finding the proper treatment dose (part 1). After that, a comparative study versus placebo will start to assess the safety and the effectiveness of the proper dose of this therapy (part 2). In the end, a follow up... (clinicaltrialsregister.eu) - P1/2 | N=61 | Recruiting | Sponsor: Genethon

New P1/2 trial • Duchenne Muscular Dystrophy • Gene Therapies • Genetic Disorders • Muscular Dystrophy

Long-term follow-up of ambulatory boys treated with GNT0004, Genethon's AAV-based gene therapy for Duchenne muscular dystrophy: Results from the phase 1/2 part of the GNT-016-MDYF clinical trial (ASGCT 2026) - "Conclusion At 3×10¹³ vg/kg, GNT0004 showed durable functional and MRI benefits along with significant and sustained CK reduction versus NH over ≥2 years, with a favorable safety profile. These results reinforce its therapeutic potential and support confirmation in the ongoing pivotal Part 2 study."

Clinical • Gene therapy • Late-breaking abstract • P1/2 data • CNS Disorders • Duchenne Muscular Dystrophy • Gene Therapies • Genetic Disorders • Muscular Dystrophy

Systemic GNT0004 Gene Therapy: Dose-Finding Study in the DMDmdx Rat Model (ASGCT 2026) - "Conclusion Systemic administration of GNT0004 restored dystrophin expression and improved both skeletal and cardiac function in DMDmdx rats. The MED is estimated to be between 1E13 and 3E13 vg/kg, supporting dose selection for clinical trial in DMD patients."

Gene therapy • Preclinical • Cardiomyopathy • Cardiovascular • CNS Disorders • Duchenne Muscular Dystrophy • Fibrosis • Gene Therapies • Immunology

GNT-016-MDYF: A clinical study in 3 parts with a microdystrophin (called GNT0004), a new gene therapy in boys with Duchenne disease who can still walk. The study will start with finding the proper treatment dose (part 1). After that, a comparative study versus placebo will start to assess the safety and the effectiveness of the proper dose of this therapy (part 2). In the end, a follow up... (clinicaltrialsregister.eu) - P1/2 | N=40 | Recruiting | Sponsor: Genethon | N=30 ➔ 40

Enrollment change • Duchenne Muscular Dystrophy • Gene Therapies • Genetic Disorders • Muscular Dystrophy

Gene therapy in Duchenne muscular dystrophy. (PubMed, Arch Pediatr) - "In 2023, delandistrogene moxeparvovec (Sarepta/Roche) received accelerated approval from the U.S. Food and Drug Administration for ambulatory pediatric patients, marking the first regulatory authorization of a gene therapy for DMD. By contrast, fordadistrogene movaparvovec (Pfizer) showed encouraging biomarker results but was associated with immune-mediated serious adverse events, including thrombotic microangiopathy cases and patient deaths due to acute liver failure, ultimately leading to program discontinuation. Other investigational candidates-GNT0004 (Généthon), SGT-003 (Solid Biosciences), and RGX-202 (Regenxbio)-incorporate distinct promoter designs and microdystrophin cassettes and are currently in early- to mid-phase evaluation...Gene therapy management also raises difficult economic and logistical challenges for healthcare systems. Balancing rapid patient access to potentially disease-modifying therapies with rigorous scientific and regulatory..."

Journal • Review • Duchenne Muscular Dystrophy • Gene Therapies • Genetic Disorders • Hepatology • Liver Failure • Muscular Dystrophy • Myositis • Pediatrics

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 (ESGCT 2024) - "Participants received immune prophylaxis with sirolimus and add-on steroids. GNT0004 administration was safe and well tolerated in the last 4 participants (including all 3 patients at dose 2). Therefore, dose 2 (3x1013vg/kg) was selected to proceed to part 2 (pivotal phase 3)."

Clinical • Gene therapy • P1/2 data • Duchenne Muscular Dystrophy • Gene Therapies • Genetic Disorders • Immunology • Muscular Dystrophy • Myositis

Step by step development of a cell-based potency assay for the gene therapy product G3MDYF/GNT0004 (rAAV8 human Microdystrophin) (ESGCT 2024) - "Since to exploit its function hMD1 must reach the membrane, in the third step we characterized the localization of the hMD1 protein by two different techniques: immunostaining to verify the colocalization between hMD1 and the dystrophin-associated protein complex (DAPC) proteins and Simple Western after subcellular fractionation to detect hMD1 protein in the membrane fraction and measure the relative potency in a dose dependent manner. We have shown the combination of different techniques to develop a robust assay for G3MDYF/GNT0004 (rAAV8 human Microdystrophin), that is fundamental for comparability studies, process validation and for stability testing."

Gene therapy • Duchenne Muscular Dystrophy • Gene Therapies • Muscular Dystrophy

Dose- and genotype-dependent cardiac arrhythmia and sudden death in rats following microdystrophin gene therapy. (PubMed, Mol Ther) - "GNT0004, a rAAV2/8 vector expressing MD1, is currently being tested in DMD patients...At this dose, increased arrhythmic risk and cardiac pathological remodeling were observed. These observations highlight the potential risk of MD overexpression in the heart and suggest a need for careful monitoring of DMD patients treated with gene therapy."

Journal • Preclinical • Cardiovascular • Duchenne Muscular Dystrophy • Gene Therapies • Genetic Disorders • Muscular Dystrophy

GNT0004, Genethon's AAV-based gene therapy for Duchenne muscular dystrophy: long-term follow-up of ambulatory boys enrolled in the dose-escalation phase of GNT-016-MDYF (ESGCT 2025) - No abstract available

Gene therapy • Late-breaking abstract • Duchenne Muscular Dystrophy • Gene Therapies • Genetic Disorders • Muscular Dystrophy

GNT0004, Genethon's AAV-based gene therapy for Duchenne muscular dystrophy: long-term follow-up of ambulatory boys enrolled in the dose-escalation phase of GNT-016-MDYF. (ASGCT 2025) - "These effects will need to be confirmed in Part 2, the pivotal phase of GNT-016-MDYF. Disease Focus of Abstract:Muscular Dystrophy (all forms)"

Gene therapy • Duchenne Muscular Dystrophy • Gene Therapies • Genetic Disorders • Infectious Disease • Muscular Dystrophy

Genethon to start international clinical trial for treatment of Duchenne muscular dystrophy (News-Medical) - "Genethon... received...the authorization from the ANSM, the French National Agency for Medicines and Health Products Safety, to start in France a multicentre international clinical trial for the treatment of Duchenne muscular dystrophy with product GNT 004. This trial's goal is to assess the safety and efficacy of an innovative gene therapy designed at Genethon..."

New trial • Duchenne Muscular Dystrophy

Genethon announces expanded collaboration with Sarepta Therapeutics (Eurekalert) - "Genethon...and Sarepta Therapeutics...announced an expansion of their collaboration to develop a gene therapy approach for Duchenne muscular dystrophy...The agreement between Sarepta and Genethon paves the way for a clinical trial to begin in 2020...Under the terms of agreement, Genethon will be responsible for commercializing the product GNT0004 in Europe (excluding the UK) and Sarepta will be responsible for the rest of the world."

Licensing / partnership • New trial