Initial results from a gene therapy trial for GNT0004, presented at the International Myology 2024 Congress, indicate positive activity in treating Duchenne muscular dystrophy (DMD). The adeno-associated virus (AAV8) vector-based gene therapy, developed by Genethon, demonstrated good tolerability and efficacy in ambulant boys aged six to ten years. The trial's innovative design incorporated Phases I/II/III with a dose escalation phase, followed by a pivotal phase at the selected dose.
GNT0004 contains a shortened, functional version of the DMD gene (hMD1) encoding dystrophin, driven by a Spc5.11 promotor to ensure expression in skeletal and cardiac muscle. Five patients were treated with GNT0004 via intravenous injection, with two receiving the first dose and three receiving the second dose (3×1013 vg/kg).
Microdystrophin Expression and CPK Levels
Results from the trial showed that the higher dose facilitated up to 85 percent of muscle fibers expressing microdystrophin eight weeks post-injection. Furthermore, twelve weeks post-treatment, a decrease in CPK levels (a biomarker of muscular distress) was observed, ranging between 50 percent and 87 percent, and persistent for up to 18 months of follow-up for the first patient treated at this dose.
Clinical Evolution and Future Plans
Genethon reported that one-year efficacy results for the first patient in cohort 2 showed a positive clinical evolution. Notably, the dose chosen for the AAV8 gene therapy was lower than those used in other gene therapy trials for Duchenne muscular dystrophy.
Following a positive opinion from the Data Monitoring Committee, Genethon is planning the pivotal European phase of the trial, marking a significant step forward in the development of GNT0004 as a potential treatment for Duchenne muscular dystrophy.
