Gene Therapy RGX-202 Continues to Increase Microdystrophin Expression in Latest Trial Update

Curran M. Simpson

Newly announced interim safety and efficacy data from the phase 1/2 AFFINITY DUCHENNE trial (NCT05693142) showed that treatment with REGENXBIO’s RGX-202 was well tolerated, with meaningful increases in expression of microdystrophin at 3 months. In addition to reductions in serum creatine kinase levels, these data support evidence of clinical improvement with RGX-202, a next-generation investigational gene therapy, for patients with Duchenne muscular dystrophy (DMD).¹

In addition to sharing positive interim data, the company noted it expects to complete enrollment in the dose level 2 expansion cohort early in the third quarter of 2024 and has initiated enrollment in the cohort for boys aged 1-3. Initiation of that pivotal trial is expected in the fourth quarter of 2024. Additionally, initial strength and functional assessment data for both dose levels of AFFINITY DUCHENNE is expected in the second half of 2024.

The data update included 7 patients who had been dosed, 3 in dose level 1 and 4 reaching dose level 2. In patients aged 5.8 and 8.5 who received the gene therapy at dose level 2, RGX-202 microdystrophin expression was measured to be 77.2%, and 46.5%, respectively compared with control at 3 months. All patients, regardless of dose level, completed 3-month assessments, with results showing meaningful increases in expression of RGX-202 microdystrophin and a reduction in serum creatinine kinase levels. For context, creatine kinase is an intracellular enzyme found in skeletal muscles, heart muscles, and the brain.

"With today's new, positive data, we are seeing a clear dose response and consistent, robust microdystrophin expression levels across all treated patients in the AFFINITY DUCHENNE trial, and, notably, among the highest levels of microdystrophin expression reported in older ambulatory patients,” Curran M. Simpson, president and chief executive officer at REGENXBIO, said in a statement.¹ "This data continues to build on the totality of evidence supporting the potential for RGX-202 to be a differentiated, best-in-class treatment for Duchenne. RGX-202 is well positioned to be the next potential gene therapy approved for Duchenne, and, with our commercial-ready, suspension-based manufacturing platform process, we believe we have the capacity to serve the entire market."

READ MORE: Pfizer Discontinues Gene Therapy Program for Duchenne Following Negative Phase 3 Results

According to REGENXBIO, RGX-202 remains the only investigational gene therapy for DMD with a differentiated microdystrophin construct that encodes key regions of naturally occurring dystrophin, including the C-terminal domain. Manufactured using REGENXBIO’s proprietary high-yielding NAVXpress suspension-based platform process, the gene therapy is designed to target expression of genes throughout skeletal and heart muscle using the NAV AAV8 vector and a well-characterized muscle-specific promoter called Spc5-12.

The trial, which began in 2023, includes 2 cohorts of patients, with the lower-dose cohort receiving 1x10¹⁴ genome copies (GC)/kg body weight and the higher-dose cohort receiving 2x10¹⁴ GC/body weight. Participants in the trial are required to have a DMD gene mutation in exons 18 and above, must be able to walk 100 meters independently without assistive devices, must be able to complete the Time to Stand Test per protocol-specific criteria, and must be on a stable dose of systemic glucocorticoids according to the standard of care for at least 12 weeks prior to screening.

Aravindhan Veerapandiyan, MD

"I remain encouraged by the biomarker data from the AFFINITY DUCHENNE trial of RGX-202 and am eagerly anticipating the initial functional data from this program," Aravindhan Veerapandiyan, MD, a pediatric neuromuscular neurologist at Arkansas Children’s Hospital, said in a statement.¹ "This update is also encouraging for the Duchenne community, which is exploring various treatment options that could influence disease progression."

These data build on previous positive findings presented at the 2023 Annual International Congress of the World Muscle Society, where the therapy was reported to be well tolerated with no therapeutic-related serious adverse events in 3 patients, aged 4.4, 10.6, and 6.3 years, dosed at the level 1 dosage. The findings, presented by Veerapandiyan, showed a 43% reduction in creatine kinase levels at 10 weeks. In addition, 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 creatine kinase levels at 10 weeks.²

REFERENCES
1. REGENXBIO announces new positive data from Affinity Duchenne trial of RGX-202. News release. REGENXBIO. August 1, 2024. Accessed August 1, 2024. https://www.prnewswire.com/news-releases/regenxbio-announces-new-positive-data-from-affinity-duchenne-trial-of-rgx-202-302212086.html
2. 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 August 1, 2024. https://regenxbio.gcs-web.com/news-releases/news-release-details/regenxbio-presents-interim-clinical-data-phase-iii-affinity