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.

Aravindhan Veerapandiyan, MD, pediatric neuromuscular neurologist at Arkansas Children's Hospital

Aravindhan Veerapandiyan, MD

Recently, additional findings from the ongoing phase 1/2 AFFINITY DUCHENNE trial (NCT05693142) of RGX-202 (REGENXBIO), an investigational adeno-associated virus (AAV) vector-based gene therapy for Duchenne muscular dystrophy (DMD), showed a reduction in key DMD measures among pediatric patients treated with the agent.1 These results suggest that the therapy demonstrates clinical improvement and thus supports the continued investigation of RGX-202 in this patient population.

At the level 1 dosage of the therapy (1x1014 genome copies [GC]/kg body weight), a patient aged 4.4 years old reported microdystrophin expression of 38.8% on RGX-202 in comparison with control. This patient also reported a 43% reduction from baseline in serum creatine kinase (CK) levels at 10 weeks. Using the same dosage, a patient aged 10.6 years old had 11.1% of RGX-202 microdystrophin expression compared with the control and reported a 44% reduction from baseline in serum CK 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 Aravindhan Veerapandiyan, MD, pediatric neuromuscular neurologist at Arkansas Children's Hospital, said in a statement.1 "I know that there is still unmet need for these boys for new treatment options that have the potential to impact the trajectory of the disease."

Presented at the 2023 Annual International Congress of the World Muscle Society, the therapy reported to be well tolerated with no therapeutic-related serious adverse effects in 3 patients, aged 4.4, 10.6, and 6.3 years, dosed at the level 1 dosage. The time of post administration follow-up ranges from 3 weeks to more than 5 months and the 2 patients who reached a 3-month follow-up completed the immunosuppression regimen.

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 one-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.

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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 genome copies (GC)/kg body weight (n =2) and the higher-dose cohort receiving 2x1014 GC/kg body weight (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 adverse events (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 which 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.”1

"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 said in a statement.1 "The unique construct of RGX-202, inclusive of the C-Terminal domain, has the potential to make a meaningful impact for patients and we are encouraged by these interim safety and efficacy results."

REGENXBIO expects to dosing 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 as well as 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 chief executive officer of REGENXBIO said in a statement.1 "We plan to scale up production of RGX-202 using commercial-ready cGMP material from the REGENXBIO Manufacturing Innovation Center to support a pivotal program in 2024, with a clear path to submit a BLA using the accelerated approval pathway, with RGX-202 microdystrophin as a surrogate endpoint for clinical benefit. This update firmly establishes RGX-202 as a key feature of our '5x'25' vision to have 5 gene therapies either on the market or in late-stage development by 2025."

1. 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.
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