Opus Genetics Accelerates AAV Gene Therapy for Leber Congenital Amaurosis Following Key FDA RMAT Feedback

NEW YORK — Nov. 7, 2025 — Opus Genetics, a clinical-stage company, has completed a crucial Type B Regenerative Medicine Advanced Therapy (RMAT) meeting with the U.S. Food and Drug Administration (FDA) regarding OPGx-LCA5, its investigational AAV gene therapy candidate for Leber congenital amaurosis (LCA) caused by mutations in the LCA5 gene.

The productive interaction with the FDA provided vital feedback on the registration strategy, including Chemistry, Manufacturing, and Controls (CMC) requirements, as well as the pivotal trial design. This feedback is expected to significantly accelerate the path to market for this sight-restoring AAV treatment.

Adaptive Trial Design Leveraging AAV Potential

George Magrath, MD, CEO of Opus Genetics, highlighted the strategic outcomes of the RMAT meeting. “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,” Dr. Magrath stated.

The company plans to incorporate the FDA’s feedback into an updated clinical development plan, which includes transitioning the ongoing Phase 1/2 trial into a Phase 3 study with as few as eight participants. This novel, adaptive design will utilize a run-in period for participants to serve as their own controls, monitoring their natural disease history before receiving the AAV gene therapy.

This investigational AAV product, OPGx-LCA5, is an AAV-delivered gene therapy designed to address LCA that results from biallelic mutations in the LCA5 gene, which encodes the lebercilin protein. The AAV vector is engineered to deliver a healthy copy of the gene, aiming to restore functional vision.

Promising Early Data and Regulatory Momentum

Earlier positive 3-month pediatric data from the Phase 1/2 trial showed significant measurable gains in vision in teenagers. Furthermore, adults treated earlier in the study have maintained visual gains out to 18 months, underscoring the potential long-term benefits of the one-time AAV administration.

The company anticipates dosing to start in the Phase 3 portion of the study in the second half of 2026, with topline results expected a year later.

Additionally, Opus Genetics announced its intent to apply for the FDA’s Rare Disease Evidence Principles (RDEP) review process. This process is intended to facilitate the approval of drugs, like this AAV gene therapy, that treat rare diseases with very small patient populations, significant unmet medical needs, and a known genetic defect that is the major driver of the pathophysiology.

The successful RMAT interaction is a critical milestone as Opus continues working closely with the FDA to bring this potential sight-restoring AAV gene therapy to patients who currently have no approved treatment options.