ViGeneron Receives FDA Authorization to Launch Clinical Trial for mRNA Trans-splicing Gene Therapy for Stargardt Disease

ViGeneron, a company developing genetic therapies for eye diseases, has received authorization from the US Food & Drug Administration (FDA) to launch a Phase 1/2 clinical trial for VG801, an emerging mRNA trans-splicing gene therapy for people with Stargardt disease and other retinal diseases caused by mutations in the gene ABCA4. The company will also seek authorization from the European Medicines Agency to conduct the clinical trial at sites in the EU. Additional details for the planned clinical trial are forthcoming.

Stargardt disease, and most other inherited retinal diseases, is caused by mutations (mistakes) in a single gene. Genes are like recipes. Information from genes is transcribed into messages called mRNA which cells read to make proteins critical to the cells’ health and function. If there is a mutation in the gene (i.e., a mistake in the recipe), it gets transferred in the mRNA, and the cell makes insufficient or incorrect proteins, leading to disease.

While many emerging retinal disease gene therapies involve delivery of an entire new gene to cells in the retina to compensate for the mutated gene, the ABCA4 gene is too large to deliver with commonly used viral delivery systems.

VG801 overcomes the delivery challenge of the large ABCA4 gene by delivering it in two halves using dual viral vectors. Once in the cell, half of the mRNA is transcribed from each gene half. VG801 uses a special biochemical process called trans splicing to bond the two mRNA halves together. The cell then reads the complete mRNA to make a functional protein. VG801 is a onetime treatment injected into the vitreous, the soft gel in the middle of the eye.

ViGeneron also announced that the FDA has selected its proposal for the Rare Disease Endpoint Advancement (RDEA) pilot program. The RDEA program is designed to foster innovation and advance rare disease drug development programs. As part of the RDEA program, ViGeneron will collaborate with the FDA throughout the novel efficacy endpoint development process. The identification of novel endpoints ¾ measures that enable clinical researchers to determine if an emerging therapy is saving or restoring vision ¾ is critical to clinical trial success and regulatory approval of the treatment. 

In April 2024, ViGeneron launched a Phase 1/2 clinical trial for a gene therapy for people with retinitis pigmentosa caused by mutations in the gene CNGA1.