REGENXBIO’s DMD Gene Therapy Well-Tolerated, Efficacy Signals Promising

RGX-202 (REGENXBIO) adeno-associated virus (AAV) gene therapy has been well-tolerated in patients with Duchenne muscular dystrophy (DMD) with initial signs of microdystrophin expression in the phase 1/2 AFFINITY trial (NCT05693142).

"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, REGENXBIO, said in a statement. "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."

Updated data from the AFFINITY trial were presented at the 28th Annual International Congress of the World Muscle Society, held on October 3-7 in Charleston, South Carolina. The data were from 3 patients aged 4.4, 10.6, and 6.3 years treated with dose level 1 (1 x 10¹⁴ genome copies (GC)/kg of RGX-202. As of September 28, the therapy has been well-tolerated with no treatment-related serious adverse events (AEs).

Initial biomarker data were reported in 2 patients that have reached 3 months of follow-up and completed the immunosuppression regimen. Investigators observed increases in RGX-202 microdystrophin expression from bicep muscle biopsies as well as by immunofluorescence staining revealing microdystrophin protein localization to the sarcolemma. Microdystrophin levels were measured by western blot and confirmed by a proprietary liquid chromatography-mass spectrometry (LC-MS) method.

The patient aged 4.4 years had 38.8% microdystrophin expression compared to control and a 43% reduction in serum creatinine kinase (CK) levels at 10 weeks. The patient aged 10.6 years had 11.1% microdystrophin expression compared to control and a 44% reduction in serum CK levels at 10 weeks.

REGENXBIO plans to dose patients at dose level 2 (2 x 10¹⁴ gc/kg) in the trial by the end of 2023. The company also announced that the trial has been accelerated, with the dose expansion phase set to begin after 2 patients instead of the previous 3.

"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," primary investigator Aravindhan Veerapandiyan, MD, pediatric neuromuscular neurologist, Arkansas Children's Hospital, added. "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."

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. October 3, 2023. https://www.prnewswire.com/news-releases/regenxbio-presents-interim-clinical-data-from-phase-iii-affinity-duchenne-trial-of-rgx-202-at-28th-annual-international-congress-of-the-world-muscle-society-301946289.html