Phase 1/2 Trial of Gene Therapy RGX-202 for DMD Now Recruiting

18 patients expected to test safety, effectiveness of investigational treatment

Joana Vindeirinho, PhD avatar

by Joana Vindeirinho, PhD |

Share this article:

Share article via email
Text reads

Regenxbio has started recruiting patients for the Phase 1/2 clinical trial to assess the safety and effectiveness of RGX-202, an investigational gene therapy for Duchenne muscular dystrophy (DMD).

The trial, called AFFINITY DUCHENNE (NCT05693142), is expected to enroll 18 DMD patients ages 4 to 11 who can walk unaided. The first trial site has opened at the Arkansas Children’s Hospital in Little Rock, with additional sites expected in Canada and Europe.

Regenxbio is also recruiting DMD patients ages 12 or younger for an observational study called AFFINITY BEYOND (NCT05683379) to screen for antibodies against adeno-associated virus variant 8 (AAV8), the viral vector used in RGX-202. The study’s site is open at Rare Disease Research in Atlanta, Georgia.

“I am pleased that we are now able to initiate the trial for RGX-202 and also begin enrollment activities in our AAV8 antibody screening study,” said Kenneth T. Mills, President and CEO of Regenxbio, in a press release.

People with DMD don’t have functional dystrophin, an important protein for muscle health and function, due to mutations in the DMD gene. This leads to cell damage during muscle contraction and results in progressive muscle degeneration.

“Duchenne muscular dystrophy is a devastating disease and there are still unmet therapeutic needs,” said Aravindhan Veerapandiyan, MD, co-director of the Muscular Dystrophy Association Care Center at Arkansas Children’s Hospital and a principal investigator in the study. “Gene therapies, like RGX-202, have the potential to impact the progressive nature of Duchenne.”

Recommended Reading
DMD cell therapy | Muscular Dystrophy News | Illustration of muscle fibers

DEC Cell Therapy Leads to Muscle Function, Dystrophin Gains in Mice

Testing RGX-202 safety, effectiveness

RGX-202 was designed to deliver muscle cells a modified gene with instructions to produce a new microdystrophin, a shorter, but functional version of dystrophin. This microdystrophin contains specific regions found in the longer dystrophin shown to improve muscle resistance and health in a mouse model of the disease, Regenxbio noted.

For this delivery, RGX-202 uses Regenxbio’s proprietary viral vector, the modified and harmless AAV8. RGX-202 also contains features that promote microdystrophin production specifically in heart and skeletal muscle, along with components that might help reduce immune responses.

RGX-202 was granted orphan drug status by the U.S. Food and Drug Administration (FDA), which is meant to facilitate and incentivize new therapy development for rare medical conditions.

Following the FDA approval to progress to clinical trials, AFFINITY DUCHENNE will assess the safety, tolerability, and efficacy of RGX-202 as well as its pharmacokinetics (the movement of a medication into, through, and out of the body) and pharmacodynamics — the effects of the medication on the body. RGX-202 is given as a single infusion into the bloodstream.

Six children with DMD mutations in exons 18 and higher, ages 4 to 11 and able to walk unaided, will be divided into groups of three. Each group will receive one of two doses of RGX-202 — 1e14 genome copies per kilogram of body weight (gc/kg) and 2e14 gc/kg. After an independent safety review, another six children can be enrolled, three for each dose, for a total of 18. Exons are the DNA bits containing information to make proteins.

The trial goals include measuring microdystrophin protein levels in muscle, monitoring immune reactions against RGX-202, and strength and functional assessments such as the North Star Ambulatory Assessment of motor abilities and timed function tests.

Regenxbio has highlighted the safety measures for the trial, which were informed by the Duchenne community and by engaging with key opinion leaders. One such measure is a short-term preventive immunosuppression regimen to reduce possible immune reactions to treatment.

Regenxbio is also launching AFFINITY BEYOND, a screening study of the prevalence of antibodies against AAV8, which may help identify participants for AFFINITY DUCHENNE and future RGX-202 trials.

“We look forward to continuing to work closely with the Duchenne community as we advance a highly differentiated product candidate developed with the potential to improve muscle strength and motor function in boys with Duchenne,” Mills said.