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Shanghai Vitalgen Advances VGR-R01 Gene Therapy to Phase 3 Trial for Bietti Crystalline Dystrophy

a year ago3 min read

Key Insights

  • Shanghai Vitalgen BioPharma has initiated a Phase 3 multicenter randomized controlled trial evaluating VGR-R01 gene therapy in 45 patients with Bietti crystalline dystrophy.

  • VGR-R01 is an AAV8 vector carrying the human CYP4v2 coding sequence designed to treat this severe genetic retinal disorder caused by CYP4V2 mutations.

  • Earlier Phase 1/2 trials demonstrated that VGR-R01 is well tolerated with a favorable safety profile and showed efficacy in improving visual function.

Shanghai Vitalgen BioPharma Co., Ltd. has advanced its investigational gene therapy VGR-R01 into a Phase 3 clinical trial for patients with Bietti crystalline dystrophy (BCD), a severe genetic retinal disorder with no current effective treatments. The multicenter, randomized controlled study will enroll 45 subjects to evaluate the efficacy and safety of this novel AAV-based gene therapy.

Trial Design and Patient Population

The Phase 3 study employs a randomized controlled design with 30 subjects receiving monocular administration of VGR-R01 in the intervention group, while 15 subjects in the control group will not receive any intervention initially. The primary endpoint focuses on assessing efficacy based on the change from baseline in best corrected visual acuity (BCVA) of the study eyes. Following completion of the trial, untreated eyes will receive VGR-R01 administration in a subsequent clinical trial.

Gene Therapy Mechanism

VGR-R01 is a novel AAV8 vector carrying the human CYP4v2 coding sequence, specifically designed to address the underlying genetic cause of Bietti crystalline dystrophy. BCD is caused by biallelic mutations in the CYP4V2 gene, making it an ideal candidate for gene replacement therapy. The therapy is administered through a single unilateral subretinal injection.

Promising Early Clinical Results

Phase 1/2 trial data presented at major scientific conferences have demonstrated encouraging results for VGR-R01. According to findings presented at the American Academy of Ophthalmology (AAO) 2024, four subjects experienced ocular inflammation associated with VGR-R01 that was inconsequential to visual acuity. The researchers concluded that "VGR-R01 is well tolerated, with favorable safety profile, and efficacy is observed."
More detailed results presented at the American Society of Gene and Cell Therapy (ASGCT) 2024 showed that VGR-R01 is safe and well tolerated, with efficacy observed across the patient population. Notably, for some subjects with extremely low vision, VGR-R01 administration significantly improved their visual function, highlighting the therapy's potential impact on patients with advanced disease.

Addressing Unmet Medical Need

Bietti crystalline dystrophy represents a significant unmet medical need in ophthalmology. As described in the clinical trial documentation, BCD is "a severe and visually threatening genetic disorder with no effective treatment." The development of VGR-R01 offers hope for patients facing progressive vision loss from this inherited retinal dystrophy.
The advancement to Phase 3 represents a critical milestone for VGR-R01, building on encouraging preliminary results from investigator-initiated trials and the ongoing Phase 1/2 patient enrollments in China. The therapy's development demonstrates the potential of AAV-based gene replacement strategies for treating inherited retinal diseases caused by single gene defects.
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