Positive pediatric data emerge from the OPGx-LCA5 phase 1/2 trial of Leber congenital amaurosis type 5

Opus Genetics today announced the positive 3-month pediatric data from its Phase 1/2 open-label, ascending-dose study of the safety and efficacy of OPGx-LCA5, an investigational gene therapy for Leber congenital amaurosis type 5 (LCA5), an ultra-rare form of childhood blindness affecting about 200 patients, according to the company press release.

OPGx-LCA5 is designed to address a form of Leber congenital amaurosis that results from biallelic mutations in the LCA5 gene, which encodes the lebercilin protein, the investigators explained.

The key findings of the trial, according to the company, showed:

• significant measurable gains in vision in teenagers
• maintenance of visual gains to 18 months in adults who were treated earlier and
• a good safety profile

George Magrath, MD, Chief Executive Officer of Opus Genetics, commented, “These pediatric results are particularly exciting, as they provide evidence that OPGx-LCA5 can potentially restore cone-mediated vision in teenagers who had already experienced profound vision loss. These outcomes, alongside observed durable improvements in adults out to 18 months, give us confidence in the potential for OPGx-LCA5 to deliver meaningful and lasting benefit to patients.”

The company is expecting to meet with the FDA in the fourth quarter of 2025 to discuss the next steps in the research.

Phase 1/2 study details

The study included three pediatric patients (aged, 16 to 17 years). All had severe baseline visual impairment and were treated with one subretinal injection of OPGx-LCA5. The investigators evaluated changes in visual acuity (VA), full-field stimulus testing (FST), and the Multi-Luminance Orientation and Mobility Test (MLoMT). The study also included three adults.

For the pediatric cohort, the early data showed an average increase of a 0.3 logarithm of the minimum angle of resolution (logMAR). The increases in VA were 0.5, 0.2, and 0.7 logMAR in patients 1, 2, and 3, at 1, 3, and 1 month, respectively. These improvements exceeded those that occurred in the adult patients.

The three pediatric patients showed improvements in the FST from 1 month. The cone sensitivity was seen to improve by more than 1 log unit to both red and blue light, indicated recovery of retinal sensitivity.

The MLoMT showed that the three patients identified more objects through the 3-month timepoint compared with baseline.

Microperimetry was able to be conducted in one of the pediatric patients, who showed early signs of fixation stability.

The press release also reported that when the data from the adults and pediatric participants were combined, the VA improvements were seen to be sustained through 18 months, underscoring the potential durability of the treatment response.

OPGx-LCA5 has been well-tolerated in all six participants treated to date. No ocular serious adverse events or dose-limiting toxicities occurred. All ocular adverse events were mild, anticipated, and unrelated to the treatment.

Tomas S. Aleman, MD, from the Scheie Eye Institute, University of Pennsylvania and principal investigator of the study, said, “Seeing pediatric participants achieve measurable improvements in VA, retinal sensitivity, and real-world navigation tasks within 3 months and adult participants maintaining those improvements is a remarkable step forward. This is important evidence supporting that gene augmentation therapy can potentially restore cone function in patients with LCA5.”