DMD gene therapy GNT0004 set to enter Phase 3 trial in Europe, US
Stable or better motor function seen in boys given higher dose in multipart study
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GNT0004, an experimental gene therapy for Duchenne muscular dystrophy (DMD), appears to be working as intended in the initial parts of a multiphase clinical trial, with benefits including stable or improved motor function.
That’s according to data presented by Genethon, the therapy’s developer, at the ASGCT Breakthroughs in Muscular Dystrophy conference, held in Chicago earlier this month.
Based on these findings, Genethon is planning to expand the GNT0004 study into its pivotal Phase 3 part next year, with sites in the U.S. and Europe. If results are positive, the company may use the trial as a basis to apply for regulatory approvals of GNT0004.
“These clinical results demonstrate that gene therapy can provide solutions to one of the most complex genetic diseases,” Frederic Revah, PhD, CEO of Genethon, said in a company press release. “Our aim is to start the confirmatory (pivotal) phase in more than 60 children in Europe in the second quarter of 2025, followed by the US.”
DMD gene therapy works to provide microdystrophin to muscle cells
DMD is caused by mutations in the gene that provides instructions to make dystrophin, a protein that acts like a shock absorber in muscle cells to cushion muscles against damage. Without functional dystrophin, muscle cells accumulate more wear-and-tear over time, ultimately resulting in characteristic DMD symptoms of progressive muscle weakness and wasting.
GNT0004 is designed to deliver a gene encoding a shortened but functional version of the dystrophin protein, called microdystrophin, to muscle cells. The one-time therapy is given by intravenous (into the vein) injection.
Genethon is running a Phase 1/2/3 trial of the therapy in boys with DMD, ages 6 to 10, who are able to walk. In the Phase 1/2 portion of the study, five children were treated with GNT0004 — two at a low dose and three at a higher dose — at sites in France and the U.K. The higher dose will be used in the upcoming Phase 3 part of the trial.
“The strength of our product lies in this selected dose, which is lower than those used in other gene therapy trials for DMD,” Revah said. “GNT0004 has the potential to be the best-in-class curative gene therapy for DMD.”
Boys given higher dose showing stable motor function 1-2 years later
Results showed that, in the three higher dose patients, an average of 54% of their muscle fibers were expressing microdystrophin protein by eight weeks after therapy administration.
Levels of creatine phosphokinase, a muscle damage marker, also decreased by an average of 74% by 12 weeks after gene therapy. This muscle damage marker has remained at lowered levels for up to 18 months in the two higher dose patients able to be evaluated at that time.
Measures of motor function one to two years following GNT0004 treatment also have been stable for these three patients, with one experiencing notable improvements in motor function. These findings are noteworthy given that, without treatment, people with DMD typically experience a gradual worsening of motor abilities over time.
“The results of treatment with our GNT0004 gene therapy are very positive in patients treated at the higher of two doses, both in terms of micro-dystrophin expression and clinical outcomes,” Revah said.
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