• First patient received dose level 2 of RGX-202, a potential one-time AAV Therapeutic for the treatment of Duchenne that includes an optimized transgene for a novel microdystrophin
  • On track for pivotal dose determination and initiation of pivotal program in 2024

REGENXBIO Inc. (Nasdaq: RGNX) today announced that the first patient received RGX-202 at dose level 2 in the Phase I/II AFFINITY DUCHENNE® trial. RGX-202 is an investigational one-time AAV Therapeutic for Duchenne muscular dystrophy (Duchenne), using the NAV® AAV8 vector to deliver a transgene for a novel microdystrophin that includes the functional elements of the C-Terminal (CT) domain as well as a muscle-specific promoter to support a targeted therapy for improved resistance to muscle damage associated with Duchenne.

“Progressing to dose level 2 is an important milestone in our updated strategic plans and for accelerating the development of RGX-202,” said Kenneth T. Mills, President and Chief Executive Officer of REGENXBIO. “There is a large unmet need for new therapies for boys with Duchenne, and the market is capable of supporting multiple gene therapies. We believe RGX-202 has unique, differentiating features that support its potential to be a best-in-class product.”

Initial biomarker data in two patients who received RGX-202 at dose level 1 who completed three-month assessment demonstrated robust RGX-202 microdystrophin expression with localization to the muscle cell membrane. In recently completed preclinical efficacy studies, RGX-202 at dose level 2 showed improvement in functional performance, compared to dose level 1, as determined by forelimb muscle strength and treadmill exhaustion in mdx mice.

REGENXBIO expects to share initial strength and functional assessment data for both dose levels and anticipates pivotal dose determination and the initiation of a pivotal program in 2024. The Company plans to use RGX-202 microdystrophin expression as a surrogate endpoint to support a Biologics License Application (BLA) filing using the accelerated approval pathway.

 

AFFINITY DUCHENNE Trial Design

The Phase I/II AFFINITY DUCHENNE trial is a multicenter, open-label dose escalation and dose expansion clinical study to evaluate the safety, tolerability and clinical efficacy of a one-time intravenous (IV) dose of RGX-202 in patients with Duchenne. In the dose evaluation phase of the trial, four ambulatory, pediatric patients (ages 4 to 11 years old) are expected to enroll in two cohorts with doses of 1×1014 (GC)/kg body weight (n=2) and 2×1014 GC/kg body weight (n=2). After an independent safety data review for each cohort, a dose expansion phase of the trial may allow for additional patients to be enrolled.

The trial design was informed by the Duchenne community and engagement with key opinion leaders, including a comprehensive, short-term, prophylactic immunosuppression regimen to proactively mitigate potential complement-mediated immunologic responses, and inclusion criteria based on dystrophin gene mutation status, including DMD gene mutations in exons 18 and above. Trial endpoints include safety, immunogenicity assessments, pharmacodynamic and pharmacokinetic measures of RGX-202, including microdystrophin protein levels in muscle, and strength and functional assessments, including the North Star Ambulatory Assessment (NSAA) and timed function tests.

 

About RGX-202

RGX-202 is designed to deliver a transgene for a novel microdystrophin that includes the functional elements of the C-Terminal (CT) domain found in naturally occurring dystrophin. Presence of the CT domain 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. Additional design features, including codon optimization and reduction of CpG content, may potentially improve gene expression, increase translational efficiency and reduce immunogenicity. RGX-202 is designed to support the delivery and targeted expression of genes throughout skeletal and heart muscle using the NAV AAV8 vector, a vector used in numerous clinical trials, and a well-characterized muscle-specific promoter (Spc5-12).

 

About Duchenne Muscular Dystrophy

Duchenne is a severe, progressive, degenerative muscle disease, affecting 1 in 3,500 to 5,000 boys born each year worldwide. Duchenne is caused by mutations in the Duchenne gene which encodes for dystrophin, a protein involved in muscle cell structure and signaling pathways. Without dystrophin, muscles throughout the body degenerate and become weak, eventually leading to loss of movement and independence, required support for breathing, cardiomyopathy and premature death.

 

Source: https://www.prnewswire.com/news-releases/regenxbio-announces-dose-escalation-in-affinity-duchenne-trial-302000151.html
GMP mRNA
Check out our AAV CDMO service to expedite your gene therapy research
About PackGene

PackGene Biotech is a world-leading CRO and CDMO, excelling in AAV vectors, mRNA, plasmid DNA, and lentiviral vector solutions. Our comprehensive offerings span from vector design and construction to AAV, lentivirus, and mRNA services. With a sharp focus on early-stage drug discovery, preclinical development, and cell and gene therapy trials, we deliver cost-effective, dependable, and scalable production solutions. Leveraging our groundbreaking π-alpha 293 AAV high-yield platform, we amplify AAV production by up to 10-fold, yielding up to 1e+17vg per batch to meet diverse commercial and clinical project needs. Moreover, our tailored mRNA and LNP products and services cater to every stage of drug and vaccine development, from research to GMP production, providing a seamless, end-to-end solution.

Related News

Scientists develop potential stealth cancer therapy

Credit: ACS Central Science (2024). DOI: 10.1021/acscentsci.4c00559Sneaking by cancer's defenses, by disguising tumor-fighting antibodies inside the molecules cancer uses to nourish tumor growth, is the basis of a novel therapy from Yale Cancer Center researchers at...

read more

Related Services