Opus Genetics, Inc. released pediatric clinical findings from its first-in-human (FIH) phase 1/2 study evaluating the OPGx-LCA5, an investigational ocular gene therapy, for the treatment of patients diagnosed with Leber congenital amaurosis (LCA) resulting from biallelic mutations in the LCA5 gene.
Can we talk about this company for a moment?
Certainly. Opus underwent a major internal change in the last 6 months when it merged with Ocuphire Pharma, Inc. to focus exclusively on inherited retinal diseases (IRDs).
And more recently: In February 2025, the FDA granted Fast Track Designation for phentolamine ophthalmic solution (POS) 0.75%.
- To note: POS 0.75% is currently under clinical investigation for visual loss (decreased visual acuity [VA]) in low light conditions (DLD) associated with keratorefractive surgery.
Got it. Now a rundown on OPGx-LCA5.
OPGx-LAC5 uses an adeno-associated virus (AAV) vector to deliver a functional LCA5 gene—which encodes a protein essential for photoreceptor function—to photoreceptors within the retina that, in turn, target LCA5.
- Its mode of delivery: A single, unilateral sub-retinal injection
- Its regulatory status: The FDA granted Rare Pediatric Disease designation in August 2024
The preclinical data: Involved LCA5-based animal and human induced pluripotent stem cells (iPSCS) that demonstrated visual function preservation when OPGx-LCA5 was administered before the disease reached its highest severity.
And its significance?
OPGx-LCA5 could potentially become the first LCA5-related IRD therapeutic available or approved for this patient base.
Got it. Next up: this trial.
The ongoing open-label and dose-escalation study (NCT05616793) is evaluating both adult and pediatric patients with the LCA5 gene.
Those details:
- Participants: estimated 15 patients diagnosed with LCA5-IRD (aged 13+)
- Setup: Three doses of OPGx-LCA5 administered in three cohorts:
- Cohort 1: low dose (1E10 vg/eye)
- 2 adults, 3 adolescents
- Cohort 2: intermediate dose (3E10 vg/eye)
- 2 adults, 3 adolescents
- Cohort 3: high dose (1E11 vg/eye)
- 2 adults, 3 adolescents
- Cohort 1: low dose (1E10 vg/eye)
- The duration: 12 months
- The outcome measures
And what’s the latest on these pediatric participants?
To start: The study began enrolling a cohort of three pediatric patients in February 2025; so far:
- Two participants have received a dose of OPGx-LCA5
- Pediatric cohort enrollment is expected to conclude in Q2 2025
And although initial data from all three patients in the cohort isn’t expected until Q3 2025, the company shared preliminary 1-month findings based on the first patient's dosing.
- The details: A 16-year-old female patient received a single subretinal injection of OPGx-LCA5.
- The data so far: A “clinically meaningful improvement in vision was observed at 1-month post-treatment,” Opus reported.
Can you get into specifics on these results?
Tomas Aleman, MD, the study’s principal investigator, noted that the preliminary data are consistent with improvements previously observed among adult participants receiving the OPGx-LCA5 injection.
“[The patient] noticed that objects were significantly brighter and was able to distinguish letters and navigate with an independence she had never had before, after only 1-month following treatment,” stated Dr. Aleman, of the Scheie Eye Institute Perelman in Philadelphia, Pennsylvania.
Circle back to that comment about OPGx-LCA5’s performance among adults.
In November 2024, the company shared that early clinical proof-of-concept data from the first three adult patients dosed demonstrated positive findings after 6 months.
The details: A “meaningful improvement” was observed in all three patients as early as 1 month after a single-dose injection of the therapeutic.
- See here for a look at the December 2024 presentation on this data.
And what’s the plan for releasing more data?
Opus is preparing to unveil 1-year findings from the study next month during the 2025 Association for Research in Vision and Ophthalmology (ARVO) meeting in Salt Lake City, Utah, on May 4.
What to expect: “Preliminary evidence that both subjective and objective signs of efficacy in these adult patients persisted for a year,” the company stated.
Gotcha. Let’s talk next steps.
Opus recently met with the FDA to discuss—along with a possible statistical analysis plan (SAP) and chemistry, manufacturing, and controls (CMC)—a potential regulatory path for its therapeutic, including the possibility for a registrational study.
The proposition: A single-arm, adaptive, pivotal study enrolling 19 patients (at a minimum).
- The primary endpoint: Would incorporate the multi-luminance orientation and mobility test (MLoMT), a virtual reality-based version of the standard MLMT (functional vision and patient mobility test).
Time-wise: Pending successful discussions with the federal agency, Opus expects to initiate this trial in Q1 2026.