DMD gene therapy leads to sustained benefits for 3 boys in trial
Motor function improved, muscle damage eased 2 years after treatment
Three boys with Duchenne muscular dystrophy (DMD) who were given the experimental gene therapy GNT0004 in a clinical trial were seeing sustained improvements in motor function and reductions in markers of muscle damage two years after the one-time treatment.
Genethon, GNT0004’s developer, presented the findings at the European Society of Gene and Cell Therapy (ESGCT) 32nd Annual Congress, held Oct. 7-10 in Seville, Spain, according to a company press release.
DMD is caused by mutations in the gene that encodes dystrophin, a protein that helps prevent muscle damage. People with DMD produce virtually no functional dystrophin protein, and as a result, muscle cells accumulate damage over time, resulting in symptoms like muscle weakness and wasting.
GNT0004 is designed to deliver to muscle cells a gene encoding microdystrophin, a shortened but functional version of the dystrophin protein, with the aim of preserving muscle health to slow disease progression. The therapy delivers its genetic payload using a viral vector, a virus that’s been engineered to deliver a therapeutic gene instead of causing infections.
Genethon is running a Phase 1/2/3 clinical trial to test GNT0004 in people with DMD. The new data come from three participants who were treated in the Phase 1/2 part of the study.
Dose being tested in Phase 3 trial
All three patients were given GNT0004 at a dose of 30 trillion vector genomes per kilogram of body weight (vg/kg); one vector genome is one particle of gene therapy. This dose is being tested in the Phase 3 part of the trial, which recently began enrolling participants.
“These patients were treated in the dose escalation portion of our Phase 1/2/3 European trial and we are excited to present these positive long-term efficacy findings as we begin the Phase 3 pivotal trial, which is under way with the first patients included in France,” said Frederic Revah, PhD, Genethon’s CEO. “The therapeutic [30 trillion] vg/kg dose administered to the three patients is lower than other DMD gene therapies and is the dose being used [in] the Phase 3 trial, which will enroll 64 boys, ages 6 to 10, who have retained their ability to walk.”
Findings from the three GMT0004-treated patients were compared against data from a natural history cohort that tracked DMD’s evolution in the absence of gene therapy. Researchers assessed various measures of motor function, including the North Star Ambulatory Assessment (NSAA). The NSAA rates motor function on a scale out of 34; an improvement of more than 2.5 points is considered clinically relevant.
After 18 months, average NSAA scores in the GMT0004-treated patients were 5.8 points better than in the natural history cohort. Other assessments, such as the time to get up from the floor or walk a short distance, also showed improvements over natural history at 18 months, and these improvements were maintained out to two years, according to Genethon.
Genethon also reported that the three patients had significant reductions in levels of creatine phosphokinase (CPK), a biomarker of muscle damage, by 75% at 18 months and 61% at two years. Measures of muscle fat fraction, a marker of muscle degeneration, also showed improvements, and no serious side effects were reported, the company said.
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