Ocugen initiates global Phase 3 trial for gene therapy OCU410 in geographic atrophy

Ocugen, Inc. has announced the dosing of the first patient in a global Phase 3 trial for its gene therapy OCU410, designed to treat geographic atrophy (GA) secondary to dry age-related macular degeneration (dAMD). The trial, named ArMaDa3 (NCT07770828), is the first pivotal gene therapy trial for GA and follows the company's receipt of Regenerative Medicine Advanced Therapy (RMAT) designation from the U.S. Food and Drug Administration (FDA).

The FDA's RMAT designation provides Ocugen with enhanced engagement throughout the development process, eligibility for accelerated approval, and priority review. This designation is expected to streamline the regulatory pathway for OCU410, a one-time subretinal gene therapy that addresses multiple disease pathways. Unlike currently approved therapies in the U.S., which address only one pathway and require ongoing intravitreal injections, OCU410 is designed to simultaneously address complement overactivation, chronic inflammation, oxidative stress, and lipid dysregulation.

"Initiating dosing in our global Phase 3 trial just weeks after receiving RMAT designation marks a defining moment for the OCU410 program and for millions of people living with geographic atrophy," stated Dr. Shankar Musunuri, Chairman, CEO, and Co-Founder of Ocugen. "Outside the U.S., there are currently no approved treatments for GA, and the existing U.S. options are limited and require repeated injections."

The Phase 3 trial, ArMaDa3, is a multicenter, randomized, controlled study enrolling 237 subjects with GA secondary to dAMD. Subjects will be randomized 2:1 to receive a single 200 µL subretinal injection of OCU410 (5×1010 vg/mL) or to an untreated control arm. The primary endpoint of the study is the rate of change of square root-transformed GA lesion area (√mm²/year) by fundus autofluorescence (FAF) at baseline, Month 4, Month 8, and Month 12, analyzed by mixed-model repeated measures (MMRM).

Secondary endpoints include the proportion of subjects with Low-Luminance Visual Acuity (LLVA) loss ≥15 Early Treatment Diabetic Retinopathy Study (ETDRS) letters at two consecutive visits through Month 12, as well as the rate of change of ellipsoid zone (EZ) area loss by spectral-domain optical coherence tomography (SD-OCT). Discussions are ongoing with the European Medicines Agency (EMA) to potentially support a marketing authorization application (MAA) in Europe with this single Phase 3 trial.

The Phase 3 program builds on 12-month data from the Phase 2 ArMaDa trial (NCT06018558), which demonstrated a 31% reduction in GA lesion area growth rate in the medium dose group compared to control at 12 months. Additionally, the medium dose group showed a 27% reduction in ellipsoid zone area loss, a structural correlate of visual function. Approximately 20% of treated subjects showed no disease progression, and 75% demonstrated more than a 30% reduction in lesion growth at 12 months. No OCU410-related serious adverse events (SAEs) or adverse events of special interest (AESIs) were reported.

"Patients with geographic atrophy continue to face irreversible structural and functional loss of the retina, along with limited treatment options," said Dr. Victor Gonzalez, a study investigator. "The OCU410 Phase 3 study provides an important opportunity to evaluate a novel, potential one-time gene therapy approach that could lessen the burden of current treatments in the U.S., which require patients to undergo multiple injections every year."

Ocugen's OCU410 is the third modifier gene therapy program to advance into late-stage development, highlighting the strength of the company's platform and its vision for delivering a one-time treatment for life. The company anticipates a Biologics License Application (BLA) filing in 2028, supported by the results of this well-defined Phase 3 program.

Geographic atrophy affects approximately 2-3 million people in the U.S. and Europe, and is a leading cause of irreversible central vision loss in older adults. The prevalence is expected to rise as the population ages, underscoring the need for effective treatments.