Opus Genetics completes enrolment in phase 3 trial of OPGx-LCA5
Opus Genetics has completed enrolment in its registrational phase 3 clinical trial of OPGx-LCA5, an investigational gene therapy for LCA5-related Leber Congenital Amaurosis (LCA).
In a nutshell:
LCA5 is a rare inherited retinal condition caused by changes in the LCA5 gene, which can lead to the progressive loss of vision from an early age. There is currently no available treatment. However, Opus Genetics is developing OPGx-LCA5, a one-time gene therapy intended to replace the faulty gene and help restore or preserve retinal function. Early trial results have shown encouraging improvements in some measures of vision, with no serious safety concerns reported. The treatment is now being studied in a registrational phase 3 clinical trial, with dosing expected to begin in late 2026 and initial results anticipated by the end of 2027. If successful and approved by regulators, OPGx-LCA5 could potentially offer the first treatment for people living with LCA5-associated inherited retinal disease. Please note that different regulatory bodies operate in the US, UK, Europe and elsewhere, and obtaining regulatory approval can take a long time, even if Opus Genetics seeks to work with all of them.
What is LCA?
Leber Congenital Amaurosis (LCA) is a rare genetic eye disease that appears at birth or in the first few months of life. The extent of vision loss varies between individuals but is generally more rapid and severe than other forms of retinal disease. LCA is actually a term given to a group of diseases that are caused by mutations in at least 25 genes.
LCA5 is caused by mutations in the LCA5 gene. Mutations in the LCA5 gene lead to the disruption of a protein called lebercilin, which is essential for light-sensing cells known as photoreceptors. In healthy eyes, lebercilin helps photoreceptors to function normally by supporting the movement of proteins between different parts of the cell. It also contributes to maintaining the photoreceptor cells’ structure and survival. When lebercilin is missing or abnormal because of mutations in the gene, photoreceptors cannot function properly. This leads to photoreceptors degenerating, causing progressive vision loss.
There are currently no available treatments for LCA5. However, Opus Genetics have an investigative treatment in development, OPGx-LCA5, which is progressing through clinical trials.
What is OPGx-LCA5?
OPGx-LCA5 is an adeno-associated viral vector gene therapy that aims to deliver a healthy copy of the LCA5 gene to the outer retina. This means that a small virus, that doesn’t cause illness in humans, is used as a delivery system to introduce or alter genetic material within cells. The therapy is delivered as a one-time subretinal injection.
Results from the phase 1/2 trial have been encouraging. They demonstrated that OPGx-LCA5 leads to improvements in cone-mediated vision, reading ability and object recognition, suggesting a meaningful impact on central vision function. These results were observed at both a six and 12-month follow-up. Importantly, there were no serious adverse events or dose-limiting toxicities.
The trial:
OPGx-LCA5 is currently being evaluated in a phase 3 registrational clinical trial, assessing the safety and efficacy of a one-time subretinal injection. Another goal of this clinical trial is to assess the natural course of the condition over six months. This is why the participants in this trial will act as their own controls for a run-in period of six months prior to any dosing.
This is a non-randomized, open-label, phase 1/2 dose-escalation study evaluating untreated patients for six months and with three doses of OPGx-LCA5. This means that participants are assigned to certain groups and that both participants and researchers know who is in which group. It also means that the dose is gradually increased across groups of participants. In early-stage clinical trials, this is common because the main focus is on safety and trying to identify the dose that is the most effective and safe.
“With enrollment now complete, we remain on track to initiate dosing in the fourth quarter of 2026, report topline data by the end of 2027, and continue advancing OPGx-LCA5 to bring the first potential treatment to patients with LCA5-associated inherited retinal disease.”- George Magrath, M.D., Chief Executive Officer, Opus Genetics
What next?
Participants are currently completing the run-in period, and Opus Genetics reportedly expects to start dosing of OPGx-LCA5 in the fourth quarter of 2026, with topline data expected by the end of 2027.
The treatment has received several Fast Track and Orphan Drug designations from the U.S Food and Drug Association (FDA) which are designed to speed up the normally lengthy review process. Opus Genetics have designed this phase 3 trial with support from the FDA as part of the Rare Disease Evidence Principles (RDEP) program. It aims to advance OPGx-LCA5 toward a Biologics License Application for what could potentially become the first approved treatment for this condition. We look forward to hearing more from Opus Genetics as the trial progresses.
Please note that different regulatory bodies operate in the U.S, U.K, Europe and elsewhere, and obtaining regulatory approval can take a long time, even if Opus Genetics seeks to work with all of them. Reaching agreement for NHS availability is a further, separate process.
To learn more about Opus Genetics and OPGx-LCA5, please visit their website here.