Ocugen Doses First Patient in Phase 3 Trial of OCU410 for GA

Ocugen has dosed the first patient in ArMaDa3 (NCT07770828), a global phase 3 registrational trial of OCU410, an investigational one-time subretinal gene therapy for geographic atrophy (GA) secondary to dry age-related macular degeneration (dAMD).¹ The trial is the first pivotal gene therapy study conducted in GA, and dosing began just weeks after the FDA granted OCU410 regenerative medicine advanced therapy (RMAT) designation on July 29, 2026.¹

OCU410 (AAV5-hRORA) delivers the human retinoid-related orphan receptor alpha gene via a single subretinal injection, designed to simultaneously address 4 pathophysiological drivers of GA: complement overactivation, chronic inflammation, oxidative stress, and lipid dysregulation.¹ This differs from currently approved complement inhibitors in the US, which target a single disease pathway and require ongoing intravitreal injections.¹ GA affects approximately 2 to 3 million people in the US and Europe and is a leading cause of irreversible central vision loss in older adults.¹

"Dosing the first patient in our global phase 3 trial, just weeks after receiving RMAT designation, marks a defining moment for the OCU410 program, and for the millions of people living with geographic atrophy," said Shankar Musunuri, PhD, chairman, chief executive officer, and co-founder of Ocugen.¹ Musunuri said outside the US there are currently no approved treatments for GA, while in the US, available options address only 1 of the 4 disease pathways and require ongoing, repeated eye injections, adding that OCU410 is the company's third modifier gene therapy program to advance into late-stage development.¹

Phase 3 design follows FDA alignment on endpoints and a single pivotal trial pathway

Dosing follows a Type B end-of-phase 2 meeting with the FDA's Center for Biologics Evaluation and Research in July 2026, which resulted in alignment on the phase 3 trial's primary and secondary endpoints, dose, adaptive design, and a single pivotal trial pathway to support a biologics license application (BLA).¹ The global, multicenter, randomized, controlled trial is enrolling 237 subjects with GA secondary to dAMD, randomized 2:1 to a single 200 µL subretinal injection of OCU410 or an untreated control arm, at sites in the US, Canada, Europe, and Latin America.¹

The primary endpoint is the rate of change of square root-transformed GA lesion area by fundus autofluorescence at baseline and months 4, 8, and 12, analyzed by a mixed model for repeated measures.¹ Secondary endpoints include the proportion of subjects with low-luminance visual acuity loss of 15 or more ETDRS letters at 2 consecutive visits through month 12 and the rate of change of ellipsoid zone area loss by spectral-domain optical coherence tomography.¹ A single adequate and well-controlled trial is intended to support a BLA filing anticipated in 2028, and Ocugen is in discussions with the European Medicines Agency regarding potential alignment to support a marketing authorization application in Europe using the same trial.¹

Phase 2 data showed a 31% reduction in lesion growth versus control

The phase 3 program and RMAT designation are supported by 12-month data from the phase 2 ArMaDa trial (NCT06018558), a multicenter, randomized, controlled study of 51 subjects with GA secondary to dAMD.¹² In the medium dose group, within the pivotal phase 3 population defined by lesion size of 2.5 to 17.5 mm2, GA lesion area growth rate was reduced by 31% versus control at 12 months (P < .05), a reduction the company said represents roughly twice the treatment benefit reported for currently approved therapies in the US at 12 and 24 months, 15% and 22%, respectively.¹ Ellipsoid zone area loss was reduced by 27% in the medium dose group versus control, and no OCU410-related serious adverse events or adverse events of special interest have been reported to date.¹ In a responder analysis of the medium dose group, approximately 20% of treated subjects showed no disease progression, and 75% demonstrated a greater than 30% reduction in lesion growth at 12 months.¹

"We are entering a global single phase 3 with a well-defined program: a dose validated in a randomized, controlled phase 2 study; an FDA-endorsed primary endpoint measuring the rate of lesion growth; and a secondary endpoint assessing functional vision," said Mohamed Genead, MD, chief medical officer of Ocugen.¹ Genead said the phase 3 program builds on compelling 12-month phase 2 data demonstrating a statistically significant 31% reduction in lesion growth with the optimal dose compared with control following a single subretinal injection, along with concordant preservation of the ellipsoid zone and no drug-related serious adverse events or adverse events of special interest.¹

RMAT designation provides OCU410 with eligibility for accelerated approval and priority review, all benefits of breakthrough therapy designation, early and frequent FDA interactions on the use of surrogate and intermediate endpoints, including the trial's fundus autofluorescence-based anatomic primary endpoint, and potential flexibility in satisfying post-approval requirements through expanded patient registries or real-world evidence.¹ OCU410 has also received advanced therapy medicinal product classification from the European Medicines Agency's Committee for Advanced Therapies.¹

Frequently Asked Questions

• What is OCU410, and how does it differ from approved GA therapies?
  OCU410 is a one-time subretinal gene therapy designed to address 4 disease pathways implicated in GA simultaneously, unlike approved complement inhibitors, which target a single pathway and require ongoing intravitreal injections.
• What did the phase 2 ArMaDa trial show?
  At 12 months, the medium dose reduced GA lesion area growth rate by 31% versus control (P < .05) and ellipsoid zone area loss by 27%, with no OCU410-related serious adverse events reported.
• What is the design of the phase 3 ArMaDa3 trial?
  ArMaDa3 is enrolling 237 subjects randomized 2:1 to a single subretinal injection of OCU410 or an untreated control, with a primary endpoint measuring rate of change in GA lesion area by fundus autofluorescence through month 12.

References

1. Ocugen, Inc. Ocugen Announces First Patient Dosed in Phase 3 Registrational Trial of OCU410 Modifier Gene Therapy for Geographic Atrophy Secondary to Dry Age-Related Macular Degeneration. News release. Published September 1, 2026. Accessed September 2, 2026. https://ir.ocugen.com/node/14881/pdf

2. ClinicalTrials.gov. A Study to Evaluate the Efficacy and Safety of OCU410 in Subjects With Geographic Atrophy (GA) Secondary to Dry Age-Related Macular Degeneration (AMD) (ArMaDa). NCT06018558. Accessed September 2, 2026. https://clinicaltrials.gov/study/NCT06018558