Opus Genetics, Inc. recently announced that the last patient has been enrolled in its registrational phase 3 clinical trial evaluating OPGx-LCA5 for LCA5-associated inherited retinal disease (IRD).
Let’s start with a refresher on Opus Genetics.
Based in Research Triangle Park, North Carolina, the clinical-stage biopharmaceutical company’s main focus is developing gene therapies to restore vision and prevent blindness in patients with IRDs.
Its pipeline: includes seven adeno-associated virus (AAV)-based gene therapy assets, with two leading candidates:
- OPGx-LCA5 for the treatment of Leber congenital amaurosis (LCA) type 5, caused by biallelic mutations in the LCA5 gene
- OPGx-BEST1 for the treatment of bestrophine-1 (BEST1)-related IRDs
Moving on to OPGx-LCA5.
LCA5 encodes lebercilin, a ciliary protein essential for protein trafficking between photoreceptor inner and outer segments; loss of this protein disrupts outer segment development, leading to profound vision loss early in life.
To address this: OPGx-LCA5 uses an AAV8 vector to precisely deliver a functional LCA5 gene to photoreceptors via a single, unilateral subretinal injection.
Now tell me more about this phase 3 study.
The candidate is currently being evaluated in a phase 1/2/3 clinical trial (NCT05616793) evaluating OPGx-LCA5 (in three doses) among adults and pediatric patients (aged 13+) with the LCA5 gene.
- See here for participant details, the setup, and outcome measures for the phase 1/2 portion of the study.
And take note: The phase 3 portion of this study was designed in collaboration with the FDA to support a potential future Biologics License Application (BLA) submission based on 6-month efficacy data, with 12-month durability data provided during review.
Got it. So how has this gene therapy performed on the regulatory side?
Most recently (in May 2026), OPGx-LCA5 was accepted into the Rare Disease Evidence Principles (RDEP) program, which provided clearer guidance on the types of evidence that can be used to demonstrate substantial evidence of effectiveness in the FDA review.
This milestone also followed three FDA designations previously awarded to OPGx-LCA5, including:
- Rare Pediatric Disease
- Orphan Drug
- Regenerative Medicine Advanced Therapy (RMAT)
And in terms of clinical efficacy and safety?
In April 2025, the company released preliminary 1-month findings based on one pediatric patient receiving a single subretinal injection of OPGx-LCA5.
Check out that data, as well as early clinical proof-of-concept data (reported before that) from the first three adult patients dosed after 6 months.
Next, refresh me on the data from the phase 1/2 portion of this study.
The most recent reporting on the study’s pediatric cohort was based on 3-month data from three patients aged 16 to 17 with severe baseline vision impairment.
Following a single subretinal injection of OPGx-LCA5, improvements were noted in four key measures of the patients’ visual function.
- Visual acuity (VA): a group average of 0.3 logMAR improvement—which was greater than that observed in the adult cohort.
- Full-field stimulus testing
- All patients demonstrated improvements in their treated eyes from 1 month and showed >1 log unit improvement in cone sensitivity to both red and blue light.
- Multi-luminance orientation and mobility test (MLoMT):
- All three patients identified more objects through the 3-month mark versus baseline, with two out of three having greater improvement in the treated eye versus the control eye.
- Microperimetry:
- At screening, two-thirds of patients could not conduct a microperimetry test due to poor VA and nystagmus
- Also worth noting: Microperimetry data was collected from one patient—who demonstrated “early fixation stability … consistent with functional retinal recovery.”
Anything else?
Opus also reported that combined adult data from the study indicated VA improvements were sustained through 18 months—“both in terms of mean change from baseline and mean interocular difference, underscoring the potential durability of the treatment response.”
Regarding safety: In all six patients (three adults and pediatric patients each) dosed to date, OPGx-LCA5 wasn “well-tolerated.”
- There have also been no ocular serious adverse events (AEs) or dose-limiting toxicities observed, and all reported ocular AEs that have been anticipated and “mild in severity”—with none related to the OPGx-LCA5 itself.
So when can we expect an update from this phase 3 portion?
With enrollment officially complete, Opus Genetics CEO George Magrath, MD, shared that they remain on track to:
- Initiate dosing in Q4 2026
- Report topline data by the end of 2027
He added: “(The company will) continue advancing OPGx-LCA5 to bring the first potential treatment to patients with LCA5-associated IRD.”
Any other future expectations?
Opus Genetics also expects forOPGx-LCA5 to add to its regulatory milestones by qualifying for a Rare Pediatric Disease Priority Review Voucher upon approval, representing a “potentially significant strategic asset.”
And in terms of the company’s other gene therapy (OPGx-BEST1): Three-month topline data from cohort 1 of the phase 1/2 BIRD-1 trial (NCT07185256) is expected to be announced in next month—with data to be presented at the annual EURETINA Congress, Oct. 1-4 in Vienna, Austria.