Exciting Breakthrough in Pediatric Gene Therapy! Opus Genetics, Inc. has shared promising results from its ongoing phase 1/2 clinical trial investigating OPGx-LCA5, a novel gene therapy designed to combat Leber congenital amaurosis type 5 (LCA5), in a cohort of young patients. This significant announcement comes on the heels of the company dosing its first participant in a different phase 3 study involving phentolamine 0.75%, while also receiving FDA approval for another investigational drug known as OPGx-BEST1.
But let's focus on the LCA5 gene therapy for a moment. Leber congenital amaurosis is a hereditary retinal disorder characterized by the degeneration and dysfunction of photoreceptors in the eye. Specifically, LCA5 occurs due to mutations in the LCA5 gene, which encodes lebercilin—a crucial protein that supports the structure and function of photoreceptors. Astonishingly, LCA5 accounts for about 2% of all LCA cases, and at this time, there is no approved treatment available for LCA5-related inherited retinal degeneration.
This leads us to the innovative OPGx-LCA5 therapeutic approach. This investigational therapy utilizes an adeno-associated virus (AAV) vector to introduce a functional LCA5 gene into photoreceptors within the retina. The therapy is administered via a singular, unilateral subretinal injection, ensuring targeted delivery of the gene crucial for restoring photoreceptor function. As of August 2024, the FDA has also given this therapy the Rare Pediatric Disease designation, highlighting its potential significance in pediatric ophthalmology.
Now, let’s delve into the clinical data. Initially, OPGx-LCA5 underwent extensive evaluation during the preclinical phase. Here, both LCA5-based animal models and human induced pluripotent stem cells (iPSCs) showcased promising preservation of visual function, particularly when the treatment was given before the disease reached its peak severity.
Fast forward to today, and we have the ongoing 12-month open-label, dose-escalation phase 1/2 trial (NCT05616793) currently assessing OPGx-LCA5 across varying doses in 15 participants, including both adults and pediatric patients aged 13 and older with known LCA5 mutations. So, what are the findings thus far?
Indeed, preliminary results were shared earlier this year. In April 2025, data from a single pediatric patient who received a subretinal injection of OPGx-LCA5 showed intriguing results, paving the way for further exploration into the efficacy of this treatment in younger age groups. Following this, new findings based on a 3-month follow-up of three patients, aged 16 to 17, who presented with severe vision impairment at baseline, were just reported. Remarkably, after the single injection, these patients exhibited improvements across four key metrics of visual function.
For example, visual acuity (VA) showed an average improvement of 0.3 logMAR in this pediatric group, exceeding what was observed in the adult participants. Each patient's individual progress is detailed further in the data reports, demonstrating that all three young patients exhibited enhanced outcomes. In terms of full-field stimulus testing, there was a notable enhancement in each patient's treated eyes compared to their function prior to treatment, with improvements exceeding one log unit in cone sensitivity to both red and blue light—a clear indication of regained retinal responsiveness. As Opus Genetics emphasized, these results are significant as they suggest recovery in retinal sensitivity.
In the multi-luminance orientation and mobility test (MLoMT), all three individuals were able to identify more objects when compared to their baseline performance, with two out of three showing greater improvement in their treated eye versus the control eye. Additionally, during the microperimetry assessments, although two-thirds of the patients were unable to complete the test due to compromised visual acuity and nystagmus, one patient displayed early signs of fixation stability which aligns with potential functional recovery of the retina.
So, what does this mean for visual acuity across all participants studied so far? There have been encouraging results overall. Opus Genetics has reported that improvements in visual acuity were also sustained through 18 months among adults involved in the trial. This long-term data reinforces the potential efficacy and durability of responses to this treatment approach.
But let’s not overlook safety. Across the six participants treated so far, which includes three adults and three pediatric patients, OPGx-LCA5 has been well-accepted, with all reported ocular adverse events being mild and anticipated, with no serious complications or dose-limiting toxicities noted.
So, why are these findings pivotal? While the study is set to continue until 2028, leading researcher Dr. Tomas S. Aleman highlighted that this evidence supports the notion of gene augmentation therapy as a viable option for potentially restoring cone function in patients suffering from LCA5.
What’s on the horizon? Opus Genetics anticipates an upcoming meeting with the FDA in the fourth quarter of 2025, signaling exciting developments ahead. We’ll be sure to keep you updated as this story progresses!
It’s a thrilling time for gene therapy, especially in the pediatric sector. What are your thoughts on the implications of this therapy for young patients? Do you think gene augmentation could become the new standard in treating inherited retinal diseases? Share your views in the comments below!
