OCU-410 Gene Therapy Preserves Visual Acuity and Slows GA Lesion Progression, with Jay Chhablani, MD

According to recent data, OCU-410 is safe, well-tolerated, and effective in preserving visual acuity and slowing the progression of lesions in patients with geographic atrophy (GA).

Presented at the 43rd Annual Scientific Meeting of the American Society of Retina Specialists in Long Beach, CA, by Jay Chhablani, MD, University of Pittsburgh, these data reflect the results of a recent phase 1/2 trial of OCU-410. This novel modifier gene therapy delivers human RORA through a single subretinal injection to patients with GA. RORA acts through a 4-way mechanism of action to regulate cellular homeostasis. This includes modulation of inflammation, lipid metabolism, oxidative stress, and complement activation.1

Based on previous studies, RORA is capable of inducing limbal stem/progenitor cells to differentiate into mature corneal epithelium cells through another molecular switch, PITX1. Additionally, RORA can dictate the differentiation of CEC by establishing promoter-anchored, lineage-specific chromatin interaction and epigenetic landscapes.2

This phase 1 trial was a multicenter, open-label, dose-escalation study, functioning in a 3+3 design wherein patients receive 200 µL of a low (2.5 x 1010 vg/mL), medium (5 x 1010 vg/mL), or high (1.5 x 1011 vg/mL) dose of OCU-410 in the eye with worse vision, as measured by best-corrected visual acuity (BCVA). A total of 9 subjects were dosed; 3 months of data were collected from all 9 patients, 6 months from 7 patients, and 9 months for 2 patients.1

The phase 2 study involved 45 patients, who were randomized 1:1:1 to either of 2 treatment groups (medium or high dose) or an untreated control group. Patients ≥50 years of age with a BCVA of ≥21 ETDRS letters (20/320 Snellen equivalent) were enrolled. Efficacy endpoints included change from baseline BCVA, low-light visual acuity (LLVA), and GA lesion size in mm2. Safety endpoints included ophthalmological changes and study-related adverse events (AEs).1

Phase 1 exhibited no AEs or serious AEs were reported as related to the study drug or procedure, such as ischemic optic neuropathy, vasculitis, endophthalmitis, and choroidal neovascularization. Patients receiving treatments exhibited a 2-line (10-letter on ETDRS) improvement in visual function compared to untreated eyes, as measured through LLVA. Treated eyes (.95 +/- .45 mm2) also showed a 44% decrease in GA lesion compared to untreated eyes (1.69 +/- .39 mm2) at 9 months. Additionally, OCU-410’s preservation of retinal tissue indicates its potential for disease stabilization.1

Presenter Jay Chhablani, MD, sat down with HCPLive to discuss the team’s findings and next steps for OCU-410. Chhablani noted the potential for OCU-410 to not only treat GA, but to prevent it as well.

“We have been looking into this data in terms of GA, as well as the ellipsoid zone, and I’m seeing that there is benefit not only on the GA but also on the EZ as well,” Chhablani told HCPLive. “So, I believe that the sooner we treat our patients, we may be able to, in fact, not only prevent progression of GA, but maybe occurrence of GA as well. Though it is still too early to comment on this, as we move forward, we may learn more data about these patients who have these early changes.”

Chhablani also highlighted the possible roadblocks to implementing OCU-410 and its accompanying procedure once it clears phase 3 testing and receives approval.

“The biggest challenge I see is that you need a surgical procedure,” Chhablani said. “It is a sub-retinal gene therapy, so it may not be very widely applicable or adopted by many people because many of the medical retina spaces may not be able to offer this treatment.”

However, Chhablani also expressed optimism about the treatment’s potential for broad acceptance, given the positive patient responses during testing and the relative simplicity of the surgery.

“I think that overall, for surgeons, this is a pretty straightforward surgery,” Chhablani commented. “And the patients are very happy with the outcome so far.”

Phase 2 of the OCU-410 investigative study has completed enrollment, and study data is actively being reviewed and evaluated.1

Editor's Note: Chhablani reports a disclosure with AbbVie.

References

1. Chhablani J, Hadziahmetovic M, Vajzovic L, Shah S, et al. Safety and Efficacy of OCU410, a Novel Modifier Gene Therapy, for Treatment of Geographic Atrophy: Phase 1/2 Study Update. Abstract presented at the 43rd Annual Scientific Meeting of the American Society of Retina Specialists in Long Beach, CA, July 30-August 2, 2025.

2. Li M, Guo H, Wang B, et al. The single-cell transcriptomic atlas and RORA-mediated 3D epigenomic remodeling in driving corneal epithelial differentiation. Nat Commun. 2024;15(1):256. Published 2024 Jan 4. doi:10.1038/s41467-023-44471-w