July 6, 2026 —
Opus Genetics announced that it has reached alignment with the U.S. Food and Drug Administration on the design of its registrational Phase 3 clinical trial evaluating OPGx-LCA5 for LCA5-associated inherited retinal disease, an ultra-rare, early-onset inherited retinal dystrophy that can cause severe childhood blindness.
The alignment followed a successful Type B meeting under the FDA’s Rare Disease Evidence Principles, or RDEP, program. Meeting minutes confirmed key elements of the planned Phase 3 study, including trial size, design, endpoint selection, and the potential timing of a future Biologics License Application.
The Phase 3 trial is expected to enroll eight participants who are able to complete microperimetry testing, with both eyes treated. The study will include a six-month run-in period, allowing each participant to serve as their own natural history control before receiving treatment. Seven of the eight planned participants have already been enrolled and are completing the run-in period. Opus expects to initiate Phase 3 dosing in the fourth quarter of 2026.
The primary efficacy endpoint will be a mean improvement of at least 7 decibels in retinal sensitivity across the central 16 test loci, a clinically meaningful measure of visual function. The study is designed with greater than 90% statistical power to detect a treatment effect of at least seven decibels.
Phase 1/2 data support the selected endpoint. Among participants able to complete microperimetry testing, Opus reported an average improvement of approximately 10.5 decibels. Pediatric participants demonstrated large gains in cone-mediated vision, while adults showed durable improvements in cone sensitivity and visual function out to 18 months.
Importantly, the FDA indicated that Opus may submit a Biologics License Application based on compelling efficacy data at the six-month primary endpoint, with 12-month durability data submitted during the BLA review process. The company said this provides a clearer regulatory path toward potential approval.
OPGx-LCA5 is designed to treat Leber congenital amaurosis caused by biallelic mutations in the LCA5 gene, which encodes the lebercilin protein. LCA5-associated inherited retinal disease is among the most severe forms of childhood blindness and currently has no approved treatment.
The investigational therapy uses an AAV8 vector to deliver a functional copy of the LCA5 gene to the outer retina. The therapeutic rationale is supported by evidence that retinal structure and visual function may be dissociated in LCA5-associated disease, suggesting that functional improvement may still be possible even in patients with severe vision loss.
OPGx-LCA5 is currently being evaluated in a Phase 1/2 trial at the University of Pennsylvania and has remained well tolerated, with no ocular serious adverse events or dose-limiting toxicities reported. The program has received Rare Pediatric Disease, Orphan Drug, and Regenerative Medicine Advanced Therapy designations from the FDA and has been accepted into the RDEP program.
If successful, OPGx-LCA5 could become a potential treatment for one of the most severe inherited retinal diseases and may also qualify for a Priority Review Voucher, which Opus described as a potentially significant strategic asset.
