Phase 1/2 Findings Highlight RGX-202’s Safety, Impact on Key Duchenne Biomarkers
RGX-202, a gene therapy for Duchenne muscular dystrophy, was well tolerated with no therapy-related serious adverse effects in 3 patients who received the level 1 dosage.
Recently, additional findings from the ongoing phase 1/2 AFFINITY DUCHENNE trial (
At the level 1 dosage of the therapy (1x1014 genome copies [gc]/kg), a patient aged 4.4 years reported microdystrophin expression of 38.8% on RGX-202 compared with a control patient. This patient also reported a 43% reduction from baseline in serum creatine kinase levels at 10 weeks. Using the same dosage, a patient aged 10.6 years had 11.1% of RGX-202 microdystrophin expression compared with the control and reported a 44% reduction from baseline in serum creatinine kinase levels at 10 weeks.
"I am encouraged by these initial results demonstrating that RGX-202 appears to be well tolerated and leads to robust microdystrophin expression in muscle tissue, which are important early findings," principal investigator
Presented at the
The initial biomarker data from those 2 patients indicated an increase in expression of microdystrophin from bicep muscle biopsies taken at 3 months following a 1-time administration of RGX-202. Notably, RGX-202 microdystrophin was detected by immunofluorescence staining throughout muscle tissue at 3 months, with the microdystrophin protein localized to the sarcolemma.
AFFINITY DUCHENNE, a multicenter, open-label trial is actively seeking to recruit ambulatory patients aged 4 to 11 years with DMD for the dose evaluation phase of the study. In this phase of the trial, 4 patients will be divided into 2 cohorts, with the lower-dose cohort receiving 1x1014 gc/kg (n =2) and the higher-dose cohort receiving 2x1014 gc/kg (n = 2). The study may recruit an additional 7 patients at a later time based on the results of an independent safety data review, raising the total to 9 patients in each cohort.
The study’s primary end point is the incidence of AE and serious AEs. Secondary end points include changes in North Star Ambulatory Assessment raw and total score, microdystrophin protein expression, and measures of pharmacokinetics and vector shedding. Of note, participants in the trial will receive a prophylactic immunosuppression regimen intended to mitigate potential complement-mediated immune responses. Although the study is primarily based in the United States, trial sites in Canada and Europe are expected to open later.
RGX-202 uses REGENXBIO’s proprietary NAV AAV8 vector and is intended to deliver a novel transgene that contains the functional elements of the C-Terminal (CT) domain seen in natural dystrophin. The company noted that the CT domain's presence “has been shown in preclinical studies to recruit several key proteins to the muscle cell membrane, leading to improved muscle resistance to contraction-induced muscle damage in dystrophic mice.”
"Duchenne is a rare degenerative disease, and without a functional dystrophin protein, muscles progressively weaken, leading to loss of mobility and declining respiratory and cardiac function," Olivier Danos, PhD, chief scientific officer of REGENXBIO,
REGENXBIO expects to dose for level 2 of the trial by the end of 2023. In addition, the trial was amended to accelerate the development of the therapy, updating the dose expansion phase of the trial to begin after 2 new patients. The company expects to share initial strength and functional assessment data for both dose levels and to make a pivotal dose determination to initiate a pivotal program for RGX-202 in 2024.
"We are pleased to share these encouraging results and updates, enabling us to accelerate our development of RGX-202 with the goal of reaching pivotal phase faster," Kenneth T. Mills, president and CEO of REGENXBIO,
Reference
REGENXBIO Presents Interim Clinical Data from Phase I/II AFFINITY DUCHENNE Trial of RGX-202 at 28th Annual International Congress of the World Muscle Society. News Release. REGENXBIO. Published October 3, 2023. Accessed October 4, 2023. https://regenxbio.gcs-web.com/news-releases/news-release-details/regenxbio-presents-interim-clinical-data-phase-iii-affinity
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