OPGX-LCA5 gene therapy phase 1/2 data support potential to restore meaningful vision

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Opus Genetics announced its 1-year clinical data that highlighted durable functional improvements after subretinal delivery of the company’s gene therapy candidate, OPGx-LCA5, in adults with Leber congenital amaurosis 5 (LCA5)-associated retinal degeneration.

Tomas Aleman, MD, from the Scheie Eye Institute, Philadelphia, reported the results of the phase 1/2 trial that showed that the treatment effects observed at 6 months were sustained at 1 year. These included measurable improvements in cone-mediated vision, reading ability, and object recognition, indicating a meaningful impact on central visual function in this severe, early-onset condition, according to the company’s press release.

Dr Aleman reported the results at the Association for Research in Vision and Ophthalmology 2025 annual meeting in Salt Lake City.

The results were obtained from three adult patients aged 19, 26, and 34 years, all of whom received subretinal injections in one eye of up to 300 µl of low-dose (1x1010vector genome (vg) per eye) OPGx-LCA5. These patients all had severe disease at baseline, with limited but detectable photoreceptors and disease that had progressed to the central retina.

The company announced the following key findings in 3 adult participants:

• The visual acuity improved an average of 0.35 logarithm of the minimum angle of resolution visual acuity (~3.5 lines).
• Light sensitivity increased by 0.86 log on full-field stimulus testing compared with 0.16 in untreated eyes).
• One patient had improved pupillary responses and microperimetry data support restoration of cone function and central fixation.
• Mobility tests using the VR-based Multi-Luminance orientation and Mobility Testshowed object detection and course completion gains.
• No dose-limiting toxicities or serious adverse events were reported through 12 months.

Dr Aleman commented, “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 6months being sustained out to 1 year.”

He continued, “The unquestionable gains in cone-mediated vision (daytime) confirmed 1 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 groundbreaking opportunities, as we look forward to enrolling additional patients into the study.”

Study design

This clinical trial (NCT05616793) evaluated the safety and preliminary efficacy of subretinal gene therapy with OPGx-LCA5 in patients with inherited retinal degeneration due to biallelic mutations in the LCA5 gene.

The study was an open-label, phase 1/2 trial evaluating OPGx-LCA5. The efficacy endpoints included the measurement of functional vision using: the Multi-Luminance Orientation and Mobility Test, which is a virtual reality-based test designed to measure changes in functional vision; the Full-Field Stimulus Testing (FST), which measures the retina's sensitivity to light; and microperimetry, which measures point-wise sensitivity to light.

In addition to the 3 adults, 2 pediatric patients also were treated, with preliminary data emerging, and Opus expects to initiate clinical trials for its second inherited retinal disease program (BEST1) later this year. The results with the pediatric patients were not included in the announced results.

The sustained improvements, particularly in cone-mediated functions like reading and object recognition support the biologic activity of LCA5 gene augmentation and provide a basis for registration trial planning with the FDA, according to the press release.