Ocugen, Inc. announced positive 12-month data from the Phase 2 ArMaDa clinical trial evaluating OCU410 (AAV5-RORA), its novel modifier gene therapy for geographic atrophy (GA) secondary to dry age-related macular degeneration (dAMD). The global prevalence of dAMD is 266 million worldwide, and GA affects approximately 2-3 million people in the United States and Europe. There are limited options for patients with dAMD in the U.S. and current therapies require 6?12 injections per year indefinitely, leading to substantial burden and significant dropout rates in real-world practice.
Outside of the U.S., there are no approved products available. Key findings from Phase 2 include: 31% reduction in lesion growth in the optimal dose (medium) group compared to control (p< 0.05), 27% slower rate of ellipsoid zone (EZ) loss compared to control, indicating structural preservation of photoreceptors, which correlates with visual function, 55% of treated patients demonstrated =30% lesion size reduction vs. control, subgroup analysis (subjects with baseline GA lesions =5 mm2 and =17.5 mm2) showed 33% reduction in lesion growth compared to control in medium dose OCU410 with similar reductions in the high dose group.
The Phase 2 clinical trial builds directly on the clean safety profile observed in Phase 1 with no OCU410-related serious adverse events observed and no cases of endophthalmitis, retinal detachment, vasculitis, choroidal neovascularization, or ischemic optic neuropathy reported to date. GA is a multifactorial disease with a complex etiology that involves genetic and environmental factors. The current treatment options for GA in the U.S. are limited to those targeting a single mechanism?the complement pathway.
By contrast, OCU410 is a first-in-class RORA-based gene therapy designed to support central retina and photoreceptor integrity through a multi-pathway mechanism?targeting drusen, inflammation, oxidative stress, and complement activation. In the Phase 2 study, the safety and efficacy of OCU410 in patients with GA secondary to dAMD are being assessed. Fifty-one (51) patients aged 50 years and older with GA lesions within the foveal or non-foveal region were randomized 1:1:1 to receive a single subretinal administration of OCU410 at a medium dose of 1 × 1010 vector genomes per eye, a high dose of 3 × 1010 vector genomes per eye, or no treatment in the control group; each injection volume was 200 microliters.
Of note, choroidal neovascularization in the fellow eye was not exclusionary, and patients with prior exposure to pegcetacoplan or avacincaptad pegol were eligible following a three-month washout. The primary endpoint was change in GA lesion size at 12 months, measured in square millimeters by fundus autofluorescence, an FDA-accepted structural endpoint used in recent GA registration trials. Exploratory endpoints included EZ preservation on OCT a key biomarker for photoreceptor integrity, which correlates with visual function.
Ocugen plans to initiate the OCU410 Phase 3 registrational trial in the third quarter of 2026 in line with the Company?s goal of three BLA filings in three years. Geographic atrophy is an advanced form of dAMD characterized by progressive degeneration of the macula, leading to irreversible central vision loss. Millions of patients worldwide are affected by GA, with a particularly high burden in aging populations in the United States and Europe.
Despite recent approvals, treatment options remain limited and require chronic intravitreal injections, underscoring the need for innovative, durable therapies that address multiple disease mechanisms. dAMD affects approximately 10 million Americans and more than 266 million people worldwide. It is characterized by the thinning of the macula, the portion of the retina responsible for clear vision in one?s direct line of sight. dAMD involves the slow deterioration of the retina with submacular drusen (small white or yellow dots on the retina), atrophy, loss of macular function, and central vision impairment.
dAMD accounts for 85-90% of all AMD cases. OCU410 is an investigational, subretinal injection, AAV5-based gene therapy that delivers RORA (retinoid-related orphan receptor alpha), a nuclear receptor that regulates key pathways involved in retinal homeostasis, including oxidative stress response, complement regulation, inflammation, and lipid metabolism. OCU410 is being developed as a one-time gene therapy for patients with GA secondary to dry AMD.
OCU410 has received Advanced Therapy Medicinal Product (ATMP) classification from the European Medicines Agency.
