Regenxbio starts pivotal trial testing DMD gene therapy RGX-202
Results could support treatment's accelerated approval by FDA
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Regenxbio has initiated the pivotal phase of a clinical trial testing its experimental gene therapy RGX-202 in boys with Duchenne muscular dystrophy (DMD).
If the results are positive, they could support the therapy’s accelerated approval by the U.S. Food and Drug Administration (FDA). Regenxbio has also announced new data showing RGX-202 treatment led to physical function gains in boys who took part in the Phase 1/2 part of the study.
“The initiation of our pivotal trial and newly released positive functional data are exciting milestones on our path to rapidly deliver RGX-202, the only next-generation gene therapy in pivotal phase, to the Duchenne community,” Curran Simpson, president and CEO of Regenxbio, said in a company press release.
The trial is being conducted as part of the AFFINITY DUCHENNE clinical trial (NCT05693142), which had been a Phase 1/2 study to identify the best dose for future testing, but was expanded to include a pivotal Phase 3 portion following discussions with the FDA.
The study’s pivotal part is expected to enroll 30 people with DMD, ages 1 and older, who are able to walk. The only gene therapy approved for DMD so far, Elevidys (delandistrogene moxeparvovec-rokl), is available in the U.S. only for patients ages 4 and older. This clinical trial will be the first DMD gene therapy to include children as young as a year, according to Regenxbio. The trial is actively recruiting participants at sites in California, Arkansas, Illinois, Texas, and Virginia.
DMD is caused by mutations in the gene that encodes dystrophin, a protein that helps prevent muscle damage. Lack of the protein in DMD leads to progressive muscle damage, which drives the disease’s symptoms.
How does RGX-202 work in DMD?
RGX-202 is designed to deliver to muscle cells a gene that encodes microdystrophin, a shortened but working version of dystrophin. The pivotal study’s main goal is to see how many participants have levels of microdystrophin at least 10% of normal dystrophin levels at 12 weeks after the gene therapy’s infusion.
Regenxbio hopes to use the study’s results to ask the FDA to grant accelerated approval to RGX-202. The accelerated approval pathway lets the FDA conditionally authorize a treatment based on early evidence that it will likely benefit patients, in this case, the microdystrophin expression may help prevent the muscle damage that drives DMD. Makers of therapies granted accelerated approval are required to run additional studies that prove the treatment actually does provide clinical benefits.
Regenxbio said it hopes to apply for accelerated approval in 2026.
RGX-202 wouldn’t be the first DMD gene therapy to come to market via accelerated approval. Elevidys, developed by Sarepta Therapeutics, was granted accelerated approval in 2023. It’s since been granted traditional approval for patients ages 4 and older who can walk, along with accelerated approval for patients in this age range who can’t walk.
“Based on the strength of the Phase [1/2] data and our positive discussions and alignment with the FDA, we are quickly advancing RGX-202 toward a [biologics license application] filing in 2026 using the accelerated approval pathway,” Simpson said. “We continue to evaluate opportunities to expand the RGX-202 program to benefit Duchenne patients worldwide.”
Results of gene therapy in Phase 1/2 study
Regenxbio has also disclosed new data from five boys who participated in the Phase 1/2 part of the study. Three of the boys were given a low dose of RGX-202, while two got a higher dose that will be used in the pivotal study.
All the boys have seen improvements or stability in measures of physical function. This differs from the typical trajectory of DMD, where motor function gets progressively worse as time goes on.
In the two boys given the dose that will be used in pivotal testing (2x10E14 genome copies per kilogram), the mean score on the North Star Ambulatory Assessment (NSAA) improved by 5.5 points in the nine months since gene therapy. Without treatment, these scores would be expected to worsen by a point or two in the same timeframe. The NSAA is a standardized measure of motor function for boys with DMD who can walk.
The data also shows evidence of microdystrophin expression at 10% or more of normal dystrophin levels for all the participants, with one showing expression upwards of 77% of normal. No serious safety issues have been reported.
“The totality of our data demonstrates that RGX-202 provides evidence of improving outcomes for boys with Duchenne and altering the trajectory of this devastating disease, with consistent, robust expression of our novel microdystrophin translating into significant clinical benefit,” Simpson said.
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