RGX-202 Is Well-Tolerated At Multiple Doses Among Patients With DMD


An interim analysis of a phase 1/2 study suggest the REGENXBIO therapy also showed efficacy signals.

Aravindhan Veerapandiyan, MD, a child neurologist and assistant professor at Arkansas Children’s Hospital (ACH), as well as the director of the Comprehensive Neuromuscular Program and codirector of the Muscular Dystrophy Association Care Center at ACH

Aravindhan Veerapandiyan, MD

(Credit: UAMS Health)

Based on an interim data presentation from the phase 1/2 AFFINIITY DUCHENNE study (NCT05693142) including 4 patients with Duchenne muscular dystrophy (DMD) who have been administered RGX-202, the gene therapy appears to be well-tolerated at both dose levels assessed with no serious adverse events (SAEs) at the 25-week point post-administration, as of the February 28, 2024, cut-off date.1

The doses assessed included 1×1014 gc/kg (n = 3) and 2×1014 gc/kg (n = 2), though the second level included data on only 1 patient, as the other had limited follow-up. The treatment is an investigational, single-use AAV therapeutic developed by REGENXBIO that utilizes the company’s NAV AAV8 vector to deliver microdystrophin that includes functional elements of the C-Terminal domain and a muscle-specific promoter to support a targeted therapy for improved resistance to muscle damage from DMD pathology.

Microdystrophin expression at the 3-month mark was deemed “robust” at both dose levels by the investigators, with levels of 38.8%, 83.4%, and 11.1% among those aged 4 to 5 years (Patient 1, age 4.4 years), 6 to 7 years (Patient 3, age 6.6 years), and 8 to 11 years at screening (Patient 2, age 10.5 years) compared with control, respectively, for those who received the lower dose. Among the 1 patient with follow-up who received the higher dose (8 to 11 years group), the expression was 75.7% compared with control levels.

RGX-202 microdystrophin was detectable by immunofluorescence staining in muscle at 3 months, with RGX-202 microdystrophin protein localized to the sarcolemma. In addition to microdystrophin expression, there was also a reported reduction from baseline in serum creatine kinase (CK) levels of 43% at 10 weeks in Patient 1, which the investigators noted was “supporting evidence of clinical improvement.” A similar reduction from baseline in serum CK levels of 44% was observed at 10 weeks in Patient 2.

The data were presented at the 2024 American Academy of Neurology Annual Meeting, held April 13-18, in Denver, Colorado, by Aravindhan Veerapandiyan, MD​, a child neurologist and assistant professor at Arkansas Children’s Hospital​ (ACH), as well as the director of the Comprehensive Neuromuscular Program and codirector of the Muscular Dystrophy Association Care Center at ACH. Similar results were presented earlier this year at the 2024 Muscular Dystrophy Association (MDA) Clinical and Scientific Conference by Veerapandiyan and colleagues.2

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“Robust RGX-202 microdystrophin expression was observed at both dose levels in all ages. Encouraging observations of early improvements in daily activities associated with strength and function in clinic and caregiver videos,” Veerapandiyan noted in the presentation. The videos included in the presentation displayed comparisons between baseline and 9 months in 2 patients for the 1-legged hop, running, walking upstairs, and lay down to stand, as well as a few other everyday activities for children, including playing outside, swimming, and riding a bike.

In the video, a mother of one of the children in the study was quoted on her son’s progress, pointing particularly to his ability to learn to ride a bike. She said, “This is the second time he is doing this in his life. He’s a little bit afraid of falling, but he can pedal the bike. He was never able to pedal a tricycle or a balanced bike before.”

Veerapandiyan added that REGENXBIO has plans to initiate pivotal trial in second half of 2024, which will use RGX-202 microdystrophin expression as a surrogate end point that is likely to predict clinical benefit​ for the study’s primary end point. The therapy was granted fast track designation by the FDA in April 2023,3 and REGENXBIO is also carrying out AFFINITY BEYOND (NCT05683379), an observational study assessing the prevalence of AAV8 antibodies in boys aged 12 years or younger with DMD that may inform further study of the treatment.

1. Veerapandiyan A. RGX-202, an Investigational Gene Therapy for the Treatment of Duchenne Muscular Dystrophy: ​ Interim Clinical Data. Presented at: 2024 AAN Annual Meeting; April 13-18; Denver, CO.
2. Veerapandiyan A, Rao V, Dastgir J, et al. RGX-202, an investigational gene therapy for the treatment of Duchenne muscular dystrophy: Interim clinical data. Presented at: 2024 MDA Clinical and Scientific Conference; March 3-6; Orlando, FL. Poster #M150
3. REGENXBIO receives FDA fast track designation for RGX-202, a novel gene therapy candidate for the treatment of Duchenne muscular dystrophy. News release. REGENXBIO Inc. April 11, 2023. Accessed April 16, 2024. https://regenxbio.gcs-web.com/news-releases/news-release-details/regenxbio-receives-fda-fast-track-designation-rgx-202-novel-gene
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