Key Takeaways

  • Ocugen has dosed the first patient in a 237-patient global phase 3 trial of OCU410 for geographic atrophy secondary to dry AMD
  • The study will evaluate a single subretinal administration of the RORA-based modifier gene therapy, with GA lesion growth serving as the primary endpoint

Ocugen has dosed the first patient in a global phase 3 registrational trial evaluating OCU410, an investigational modifier gene therapy for geographic atrophy (GA) secondary to dry age-related macular degeneration (AMD).

The milestone follows the FDA’s July 29, 2026, regenerative medicine advanced therapy (RMAT) designation for OCU410 and completion of a Type B end-of-phase 2 meeting with the agency’s Center for Biologics Evaluation and Research (CBER). According to Ocugen, the meeting resulted in alignment on key elements of the phase 3 program, including its endpoints, dose, adaptive design and use of a single pivotal trial to support a biologics license application (BLA).

“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,” Shankar Musunuri, PhD, MBA, chairman, CEO and co-founder of Ocugen, said in a news release.

OCU410 uses an AAV5 vector to deliver the human retinoid-related orphan receptor alpha (RORA) modifier gene through a single subretinal injection. The investigational therapy is designed to address multiple pathways implicated in GA, including complement overactivation, chronic inflammation, oxidative stress and lipid dysregulation.

The global, multicenter, randomized, controlled phase 3 study is expected to enroll 237 patients with GA secondary to dry AMD at sites in the United States, Canada, Europe and Latin America. Participants will be randomized 2:1 to receive either a single 200-µL subretinal injection of OCU410 at 5 × 10^10 vg/mL or no treatment.

The primary endpoint is the rate of change in square root-transformed GA lesion area, measured by fundus autofluorescence at baseline and months 4, 8 and 12 and analyzed using a mixed model for repeated measures.

Secondary endpoints include the proportion of patients experiencing a loss of at least 15 ETDRS letters in low-luminance visual acuity at 2 consecutive visits through month 12. Investigators will also evaluate the rate of ellipsoid zone area loss using spectral-domain optical coherence tomography.

“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,” Mohamed Genead, MD, chief medical officer of Ocugen, said in the announcement.

Ocugen said the trial is intended to provide the pivotal evidence supporting a BLA submission, which the company anticipates in 2028. Discussions with the European Medicines Agency are ongoing regarding whether the same phase 3 trial could support a marketing authorization application in Europe.

The phase 3 program builds on 12-month findings from the phase 2 ArMaDa study, a multicenter, randomized, controlled trial involving 51 patients with GA secondary to dry AMD.

According to Ocugen, the medium dose selected for phase 3 produced a statistically significant 31% reduction in the GA lesion area growth rate compared with control at 12 months among patients meeting the phase 3 lesion-size criteria of 2.5 mm² to 17.5 mm². The company also reported a 27% reduction in ellipsoid zone area loss compared with control. In a responder analysis, approximately 20% of patients receiving the medium dose showed no disease progression, while 75% demonstrated greater than a 30% reduction in lesion growth at 12 months.

No OCU410-related serious adverse events or adverse events of special interest have been reported to date, according to the company.

Ocugen is positioning OCU410 as a potential one-time treatment that differs mechanistically and administratively from the intravitreal complement inhibitors currently approved for GA in the United States.