MDA 2025: DMD gene therapy RGX-202 well tolerated, data show
Treatment leads to improved motor function in DMD boys, per interim data
RGX-202, a one-time gene therapy designed to treat Duchenne muscular dystrophy (DMD), has been well tolerated in an ongoing clinical trial, with no serious side effects reported.
Interim data from the Phase 1/2 part of the trial, which is sponsored by RGX-202’s developer Regenxbio, also indicate that RGX-202 appears to be working as intended, robustly increasing the production of microdystrophin and leading to improvements in motor function for DMD boys.
Carolina Tesi-Rocha, MD, an investigator on the trial and a professor at Stanford University, shared the findings at the Muscular Dystrophy Association (MDA) annual meeting, in the presentation, “RGX-202, an investigational gene therapy for the treatment of Duchenne Muscular Dystrophy: Interim clinical data.”
DMD is caused by mutations in the gene that provides instructions to make dystrophin, a protein that normally helps prevent muscle damage. People with DMD produce little to no functional dystrophin, leading to muscular dystrophy symptoms such as progressive muscle weakness and wasting.
RGX-202 is designed to deliver to muscle cells a gene encoding microdystrophin, a shortened but functional version of the dystrophin protein, with the aim of preventing muscle damage and slowing DMD progression.
Microdystrophin version aims to promote muscle health
The treatment’s mechanism is similar to that of Elevidys (delandistrogene moxeparvovec-rokl), which is currently the only approved gene therapy for DMD in the U.S. However, the specific version of microdystrophin in RGX-202 is more similar to naturally occurring dystrophin, carrying a protein segment called the C-Terminal domain that’s expected to make it better at maintaining muscle health.
Regenxbio is running a Phase 1/2/3 clinical trial called AFFINITY DUCHENNE (NCT05693142), which is testing RGX-202 in boys and men with DMD ages 1 and older. An initial Phase 1/2 portion is testing two doses of the gene therapy in up to 15 participants, and a pivotal Phase 3 part is actively recruiting participants at six locations in the U.S.
The MDA presentation covered interim safety data from 12 boys participating in the AFFINITY DUCHENNE Phase 1/2 portion. These boys ranged in age from 1 to 11. Three of them were given a lower dose of RGX-202 (10 trillion genome copies per kg of body weight) and the rest were given a higher dose (20 genome copies/kg).
The gene therapy has been overall well tolerated in all patients. The most common side effects associated with RGX-202 were nausea, vomiting, and fatigue, and no serious side effects have been reported.
“I’m happy to report that there have been no serious adverse events throughout the trial so far,” Tesi-Rocha said.
Data also indicate that RGX-202 is leading to microdystrophin production in muscle cells as designed. In boys given the lower dose, microdystrophin ranged from 10.4% to 83.4% of dystrophin levels typically seen in people without DMD. In boys given the higher dose, microdystrophin ranged from 20.8% to more than 120%.
The microdystrophin protein was also located in the sarcolemma, the part of muscle cells where dystrophin is normally found.
“At both dose levels, RGX-202 has been well tolerated and demonstrated robust RGX-202 microdystrophin expression in boys with DMD 4-12 years of age,” the researchers wrote in their abstract.
Stronger muscles
In addition to effectively delivering the microdystrophin gene as designed, early data suggest that RGX-202 is improving muscle strength for boys. For the three boys given a low dose, a decrease has been observed in the time it takes them to stand, go up a set of stairs, or walk 10 meters (about 33 feet) at one year after gene therapy.
Scores on the North Star Ambulatory Assessment (NSAA), which measures motor function in DMD boys who retain the ability to walk, also improved in the year following gene therapy.
Motor function data were available for two boys given the higher dose. They also have shown shorter times to stand, climb stairs, or walk 10 meters, as well as improvements in NSAA scores.
Tesi-Rocha noted that these data markedly contrast with the typical trajectory of DMD, in which NSAA scores get worse over time and progressive muscle weakness makes patients take longer to stand, walk, or climb stairs. The extent of improvements seen on these functional measures was also generally larger than the minimal difference that’s considered clinically important.
“Participants treated with RGX-202 demonstrated clinically meaningful improvement in functional outcomes at both dose levels that exceeded comparisons using natural history external cohorts and [minimally clinically important difference],” Tesi-Rocha said.
The researcher also noted that the children’s caregivers have reported improvements in day-to-day life, such as better ability to ride a bicycle and engage in sports and other recreational activities with peers.
The company is now running the Phase 3 portion of AFFINITY DUCHENNE, which will evaluate the higher RGX-202 dose in about 30 boys and men, ages 1 and older. The main goal is to determine the proportion of patients whose microdystrophin levels reach at least 10% of normal dystrophin levels at 12 weeks.
Regenxbio hopes these findings will provide the basis for requesting accelerated approval of RGX-002 from the U.S. Food and Drug Administration. This is a conditional approval that is granted based on a surrogate measure that is expected to predict clinical benefit. Elevidys, developed by Sarepta Therapeutics, was also granted accelerated approval for some DMD patients in 2023.
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