Opus Genetics Inc., (NASDAQ: IRD), based in Raleigh, North Carolina, has announced the one-year summary results from adult patients treated in an ongoing Phase 1/2 study of the gene therapy candidate: OPGx-LCA5, an experimental treatment for Leber congenital amaurosis (LCA). OPGx-LCA5 is an adeno-associated virus 8 (AAV8) vector designed to deliver a functional LCA5 gene to the outer retina in patients. Following a presentation at the 2025 annual meeting of the Association for Research in Vision and Ophthalmology (ARVO), in Salt Lake City, Utah, Dr. Aleman, of the Scheie Eye Institute, University of Pennsylvania, stated that, “the preliminary data emerging from this Phase 1/2 study of OPGx-LCA5 are very encouraging. We are pleased to see evidence of durable efficacy, with the treatment benefits observed at six months being sustained out to one year. Unquestionable gains in cone-mediated vision (daytime) confirmed one year after treatment have been associated with improvements in patients’ reading vision and ability to recognize objects, which are meaningful to these patients with severely impaired visual function. These findings support continued development of this gene therapy, which offers potentially ground breaking opportunities, as we look forward to enrolling additional patients into the study.”
Previously defined as a juvenile form of RP (retinitis pigmentosa), LCA is a severe congenital or early infant-onset form of non-syndromic retinal disease, characterised by severe retinal dystrophy, vision loss, nystagmus, an absence of a normal pupil response and an almost non-recordable ERG. To date, there are now 25 genes causative for LCA, one of which, lebercilin (LCA5), now accounts ~ 2% of LCA cases with a particularly severe form of the disease. The LCA5 gene, located in chromosome 6q14.1, encodes an 80kDa protein expressed in the connecting cilium of photoreceptors. In a Phase 1 / 2 clinical study, the trial was designed to evaluate the safety and preliminary efficacy of OPGx-LCA5 in patients, diagnosed with inherited retinal degeneration due to biallelic mutations in LCA5. Efficacy endpoints include measurement of functional vision using: 1) the Multi-Luminance orientation and Mobility Test (MLoMT), similar to a primary endpoint that was approved by the FDA in 2017 for the treatment of LCA2 (voretigene neparvovec (Luxturna)); 2) Full-Field Stimulus Testing (FST); and 3) microperimetry, details available on NCT05616793 cliniclatrials.gov.
Figure 1. MLoMT assay, developed by Opus Genetics Inc., provides a virtual reality-based test designed to measure changes in functional vision; the MLoMT assay provides a “second generation” mobility test, the “MLMT” which was used as a primary endpoint approved by the FDA for voretigene neparvovec in Dec. 2027. Summary data of the MLoMT is available at the public Opus Genetics Inc., website, Corporate Presentation of May 5th 2025: https://d1io3yog0oux5.cloudfront.net/_7d861fc3e29b54997eb3d39d2d8ff0fe/ocuphire/db/453/5871/pdf/Opus+Corporate+Deck+May+2025+FINAL+%28002%29.pdf
Following the 1-year results of OPGx-LCA5, summary data reported that the MLoMT assay, a virtual reality-based test designed to measure changes in functional vision, showed that two out of the three participants had a clinically meaningful improvement, while one of the participants were unable to complete the MLoMT course. Visual acuity improvements averaged 0.35 logMAR, equivalent to a 3.5 line improvement across three participants. FST measurements showed improvements in sensitivity from baseline, with a 0.86 log improvement being observed at 12 months vs 0.16 log units for the control eyes. Finally, in microperimetry, capable for correlating functional information (visual field testing) with structural/anatomical data (retinal imaging), indicated that one patient saw substantial improvements in macular sensitivity, suggesting improved central vision with improved fixation. However, data of the other two participants could not be collected due to poor fixation at the baseline visit. Safety was well tolerated with no reports of dose-limiting toxicities or serious adverse events out to 12 months. Commenting on the announcement, George Magrath, M.D., Chief Executive Officer of Opus Genetics, stated that, “the new data, while in a limited number of adults patients, give us even more conviction that our initial success with OPGx-LCA5 has the potential to translate to the rest of our pipeline, which contains gene therapy treatments for six additional inherited retinal diseases, as we plan to enter Phase 1/2 with our BEST-1 program later this year.”