Opus Genetics Advances OPGx-LCA5 Gene Therapy for LCA Following FDA Guidance

Opus Genetics has announced a key regulatory milestone in the development of its gene therapy candidate OPGx-LCA5 for Leber congenital amaurosis type 5 (LCA5), following a successful Type B Regenerative Medicine Advanced Therapy (RMAT) meeting with the U.S. Food and Drug Administration (FDA). The discussion offered constructive feedback on pivotal trial design and manufacturing, reinforcing the FDA’s ongoing support for therapies addressing rare genetic diseases.

FDA Reaffirms Support for Rare Retinal Diseases

The FDA acknowledged the significant unmet medical need in individuals affected by LCA5-related blindness, an ultra-rare inherited retinal disease impacting approximately 200 people worldwide. The agency reaffirmed its commitment to regulatory flexibility in the development of treatments for rare conditions and provided guidance on Chemistry, Manufacturing and Controls (CMC) and trial planning.

“The FDA’s guidance provides confidence in our path to approval for OPGx-LCA5,” said George Magrath, Chief Executive Officer of Opus Genetics. “Importantly, we expect to be able to advance our ongoing trial using an adaptive design that includes a phase 3 portion which will avoid the requirement for a separate registrational trial.”

About OPGx-LCA5 Gene Therapy

OPGx-LCA5 is designed to address Leber congenital amaurosis caused by mutations in the LCA5 gene, using an adeno-associated virus 8 (AAV8) vector to deliver a functional copy of the LCA5 gene directly to the outer retina. There are currently no approved therapies for LCA5-related inherited retinal degeneration.

Encouraging Phase 1/2 Clinical Results

In the Phase 1/2 portion of the clinical trial, six late-stage participants treated with OPGx-LCA5 showed clinically meaningful improvements in vision, with no dose-limiting toxicities or ocular serious adverse events. In particular, the adult cohort demonstrated durable improvements in cone sensitivity and visual function, with benefits lasting up to 18 months post-treatment.

Adaptive Phase 3 Trial Design and Timeline

Opus plans to proceed with an adaptive Phase 3 trial design that could enroll as few as eight participants in a single-arm, 12-month study. This portion of the trial will feature a run-in period to document natural disease progression, with patients serving as their own controls. The first participant has already been enrolled in the run-in phase, and dosing is expected in the second half of 2026, with topline results anticipated in 2027.

Regulatory Pathway and Designations

Opus also plans to apply for the FDA’s Rare Disease Evidence Principles review pathway, introduced in September 2025, which is intended to streamline development for therapies targeting populations of fewer than 1,000 patients. OPGx-LCA5 has already received several important designations from the FDA, including Rare Pediatric Disease, Orphan Drug, and Regenerative Medicine Advanced Therapy (RMAT) status.