MALVERN, PA — Ocugen Inc. (Nasdaq: OCGN) has dosed the first patient in a global Phase 3 trial of OCU410, moving its one-time gene therapy for geographic atrophy into pivotal testing as the company targets a 2028 biologics license application.
The ArMaDa3 study, NCT07770828, is designed as a single registrational trial enrolling 237 patients with geographic atrophy secondary to dry age-related macular degeneration across the U.S., Canada, Europe and Latin America.
Participants will be randomized 2-to-1 to receive either a single subretinal injection of OCU410 or no treatment. The study’s primary endpoint measures the rate of change in geographic atrophy lesion area over 12 months using fundus autofluorescence imaging.
Ocugen said the trial design followed an end-of-Phase 2 meeting with the U.S. Food and Drug Administration’s Center for Biologics Evaluation and Research in July, with agreement on the dose, primary and secondary endpoints, adaptive design and use of a single pivotal study to support a potential Biologics License Application.
The company expects to file that application in 2028 if the Phase 3 program is successful. It is also discussing the study design with the European Medicines Agency as a possible basis for a European marketing authorization application.
OCU410 uses an AAV5 vector to deliver the human retinoid-related orphan receptor alpha, or RORA, gene. Ocugen is developing the therapy as a single-dose approach intended to affect multiple biological pathways implicated in geographic atrophy, including complement overactivation, chronic inflammation, oxidative stress and lipid dysregulation.
That approach differs from complement inhibitors currently approved in the U.S., which target individual pathways and require repeated intravitreal injections.
“Patients with geographic atrophy continue to face irreversible structural and functional loss of the retina, along with limited treatment options,” study investigator Victor Gonzalez said. He said the Phase 3 trial will test whether a one-time gene therapy could reduce the treatment burden associated with repeated injections.
The FDA granted OCU410 Regenerative Medicine Advanced Therapy designation on July 29 based on Phase 2 clinical data, according to Ocugen.
RMAT designation provides increased interaction with the agency and makes the program eligible for regulatory mechanisms that can include accelerated approval and priority review. It does not constitute approval of the therapy.
The Phase 3 program builds on 12-month results from Ocugen’s 51-patient Phase 2 ArMaDa study. The company reported a 31% reduction in geographic atrophy lesion growth in the medium-dose group compared with control among patients meeting the planned Phase 3 lesion-size criteria, with statistical significance at p<0.05.
Ocugen also reported a 27% reduction in ellipsoid-zone area loss in the medium-dose group. About 20% of treated patients in that cohort showed no disease progression, while 75% had more than a 30% reduction in lesion growth at 12 months, according to the company.
No OCU410-related serious adverse events or adverse events of special interest had been reported in the Phase 2 program as of the company’s update.
Chief Medical Officer Mohamed Genead said the Phase 3 study uses “a dose validated in a randomized, controlled Phase 2 study” and an FDA-aligned primary endpoint measuring lesion growth, paired with a secondary measure of functional vision.
The trial’s secondary endpoints include the proportion of patients losing at least 15 letters of low-luminance visual acuity at two consecutive visits through month 12 and the rate of ellipsoid-zone area loss measured by optical coherence tomography.
Geographic atrophy affects an estimated 2 million to 3 million people in the U.S. and Europe, according to Ocugen, and is a major cause of irreversible central vision loss in older adults.
OCU410 has also received Advanced Therapy Medicinal Product classification from the European Medicines Agency’s Committee for Advanced Therapies.
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