The Phase 3 portion of a clinical trial testing RGX-202, an investigational gene therapy for Duchenne muscular dystrophy (DMD), met its main goal, the therapy’s developer, Regenxbio, announced in a press release.
Steve Pakola, MD, Regenxbio’s chief medical officer, said the data “support the potential of RGX-202 to become a best-in-class gene therapy for Duchenne patients.”
Based on these positive data, Regenxbio is planning to ask the U.S. Food and Drug Administration (FDA) to grant accelerated approval to RGX-202. Accelerated approval allows the FDA to approve a therapy based on early evidence, such as a biomarker, that is reasonably likely to predict clinical benefit. If granted, Regenxbio would be required to run additional testing to confirm the therapy’s benefits, and approval could be withdrawn if those benefits are not confirmed.
Regenxbio said it is preparing for a potential commercial launch of RGX-202 in the U.S. in 2027.
Regenxbio plans FDA approval request
“These topline results are exciting for the Duchenne community,” said Pat Furlong, founding president of Parent Project for Muscular Dystrophy. “For decades, our community has pushed for therapies that can change the trajectory of this disease, and today’s news gives us renewed optimism. Our families cannot wait; regulatory flexibility for innovative medicines to treat rare disease remains an urgent priority. We applaud the dedication of the patients and families who participated in this research and look forward to continued progress toward delivering stronger futures for people with Duchenne.”
DMD is a genetic disease marked by a lack of dystrophin, a protein that’s vital for preserving muscle health. RGX-202 is designed to deliver a gene encoding microdystrophin, a shortened but functional version of this protein, to muscle cells.
In the Phase 3 portion of the Phase 1/2/3 AFFINITY DUCHENNE clinical trial (NCT05693142), the main goal was to see how many patients given one-time RGX-202 treatment would achieve microdystrophin levels equivalent to at least 10% of the dystrophin levels typically seen in people without DMD.
Biomarker data were available for 30 of the 31 boys treated in the Phase 3 portion of the trial. All were ages 1 and older and able to walk when they received RGX-202. Results showed 93% had at least 10% microdystrophin expression, with 80% of participants achieving levels higher than 40%.
The average microdystrophin level across all participants with available biomarker data was 71.1%, though in boys ages 8 and older, average levels were somewhat lower at 41.6%. Of note, the microdystrophin protein was located at the sarcolemma, the muscle-cell membrane where dystrophin is normally found.
Interim function data show early gains
Available one-year motor function data from nine boys ages 5 to 12 suggested RGX-202 was associated with better motor function than would be expected based on external control data from untreated DMD. The improvements in motor function scores were correlated with increased microdystrophin expression; in other words, patients with higher protein expression tended to have greater motor function improvements.
This correlation is particularly noteworthy because Regenxbio is hoping to use the microdystrophin expression data as the basis for its application requesting FDA accelerated approval. Regenxbio said the correlation supports using microdystrophin expression as a surrogate endpoint for clinical benefit in DMD.
“RGX-202 is the first gene therapy in development for Duchenne to demonstrate strong, statistically significant correlation between microdystrophin expression and functional improvement, a landmark distinction in the field,” Pakola noted.
Safety data, covering a total of 31 patients in the Phase 3 study, showed that RGX-202 was generally well tolerated. The most common drug-related adverse events were vomiting, fatigue, and nausea, all of which were mild or moderate. Only two serious adverse events were reported: one case of asymptomatic liver injury and one case of subacute myocarditis, or heart muscle inflammation. Both serious events were managed and resolved within weeks without lasting complications, Regenxbio reported.
“It’s encouraging to see robust microdystrophin expression, correlation with functional outcomes, and a manageable safety profile. These data give us hope and reinforce the potential of RGX-202 to positively impact disease progression in individuals with Duchenne,” said Aravindhan Veerapandiyan, MD, principal investigator of the study at Arkansas Children’s Hospital.
Overall, the biomarker and safety data seen in the Phase 3 portion of AFFINITY DUCHENNE build on previously reported findings from the earlier parts of the trial. A confirmatory trial will test RGX-202 in an additional 30 patients. Regenxbio said the confirmatory study has already enrolled more than 20 participants and expects to complete dosing across all 60 patients in the pivotal and confirmatory trials by mid-year.
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