Phase 2 topline data: Ocugen OCU410 reduces geographic atrophy lesion growth by 31% at 12 months

Ocugen reported topline 12-month results from its phase 2 ArMaDa clinical trial evaluating OCU410 (AAV5-RORA), an investigational modifier gene therapy for geographic atrophy (GA) secondary to dry age-related macular degeneration (dAMD).¹ The data demonstrated a statistically significant reduction in lesion progression and a safety profile consistent with earlier-phase findings.^1,2

Efficacy and safety findings

In the study, the optimal medium-dose group achieved a 31% reduction in GA lesion growth compared with control at 12 months (P < .05), meeting the primary end point, according to the company. Additional structural outcomes included a 27% slower rate of ellipsoid zone (EZ) loss versus control, suggesting preservation of photoreceptor integrity.¹ Investigators also reported that 55% of treated participants experienced at least a 30% reduction in lesion size relative to control.¹ Subgroup analyses of patients with baseline GA lesions between ≥5 mm² and ≤17.5 mm² showed a 33% reduction in lesion growth in the medium-dose cohort, with similar findings observed in the high-dose group.¹

Safety outcomes remained favorable. No serious adverse events and no adverse events of special interest related to OCU410 were reported through the 12-month timepoint. There were no reported cases of endophthalmitis, retinal detachment, vasculitis, choroidal neovascularization, or ischemic optic neuropathy.¹

Mechanism of action

OCU410 is an investigational subretinal, AAV5-based gene therapy designed to deliver RORA (retinoid-related orphan receptor alpha), a nuclear receptor that regulates multiple pathways involved in retinal homeostasis, including oxidative stress response, inflammation, complement activity, and lipid metabolism. The therapy is being developed as a one-time treatment intended to address the multifactorial nature of GA, in contrast to currently available therapies that primarily target the complement pathway.¹

“Our phase 2 data consistently demonstrates statistically significant reduction of GA lesion growth after treatment with OCU410 optimal dose, and we continue to benchmark these results against natural history data to contextualize the magnitude of effect,” Huma Qamar, MD, MPH, CMI, chief medical officer of Ocugen, said in a statement.¹

Clinical perspective

Clinical experts highlighted both the structural findings and the potential to reduce long-term treatment burden. “There remains a considerable unmet need in treating patients with GA and I am encouraged by the various analyses of the Phase 2 OCU410 data,” said Lejla Vajzovic, MD, FASRS, director, Duke University Eye Center Surgical Vitreoretinal Fellowship Program, associate professor of ophthalmology with tenure, Adult and Pediatric Vitreoretinal Surgery and Disease, Duke University Eye Center, and chair, Ocugen Retina Scientific Advisory Board.¹ She noted that the therapy may help reduce reliance on frequent intravitreal injections and associated patient fatigue.

Study design and end points

The phase 2 trial enrolled 51 patients aged 50 years and older with GA lesions located in the foveal or non-foveal region. Participants were randomly assigned in a 1:1:1 ratio to receive a single subretinal injection of medium-dose OCU410 (1 × 10¹⁰ vector genomes per eye), high-dose OCU410 (3 × 10¹⁰ vector genomes per eye), or no treatment, according to the company. Each injection was administered at a volume of 200 microliters. Prior treatment with complement inhibitors such as pegcetacoplan or avacincaptad pegol was permitted following a washout period, and the presence of choroidal neovascularization in the fellow eye was not exclusionary.¹

The primary end point was the change in GA lesion area at 12 months as measured by fundus autofluorescence, an imaging-based structural endpoint used in recent GA clinical trials. Exploratory endpoints included ellipsoid zone integrity assessed via optical coherence tomography, a biomarker associated with photoreceptor health and visual function.

“Now we can move on to phase 3 with a high degree of confidence,” according to Shankar Musunuri, chairman, CEO, and co-founder of Ocugen, referencing the transition toward a planned confirmatory study.¹

Ocugen noted it plans to initiate its phase 3 registrational trial in the third quarter of 2026, advancing the program toward potential regulatory submissions.¹

References

1. Ocugen announces topline 12-month data from phase 2 ArMaDa clinical trial evaluating OCU410 modifier gene therapy for geographic atrophy secondary to dry age-related macular degeneration. News release. March 24, 2026. Accessed March 24, 2026. https://ir.ocugen.com/news-releases/news-release-details/ocugen-announces-topline-12-month-data-phase-2-armada-clinical

2. Harp MD. Ocugen releases positive preliminary 12-month data from phase 2 ArMaDa trial. Ophthalmology Times. January 15, 2026. Accessed March 24, 2026. https://www.ophthalmologytimes.com/view/ocugen-releases-positive-preliminary-12-month-data-from-phase-2-armada-trial