First patient dosed in OCU410 phase 3 trial for geographic atrophy

Ocugen, Inc. announced that the first patient has been dosed in the ArMaDa3 (NCT07770828) global, phase 3, registrational trial evaluating OCU410 (AAV5-hRORA), a modifier gene therapy for geographic atrophy (GA) secondary to dry age-related macular degeneration (dAMD).

The key points announced in the company press release were as follows:

• This study is the first pivotal gene therapy trial to evaluate OCU410 in patients with GA secondary to dAMD.
• The FDA designated OCU410 as a Regenerative Medicine Advanced Therapy (RMAT), which provides enhanced agency interaction during development and potential opportunities for expedited review. The European Medicines Agency also designated OCU410 as an Advanced Therapy Medicinal Product.
• OCU410 is a one-time subretinal treatment that is intended to address multiple disease pathways, which differs from currently approved complement inhibitors that address only one disease pathway and require regular and ongoing intravitreal injections.
• The phase 2 ArMaDa study showed that at 12 months OCU410 achieved a 31% reduction in the growth of GA lesions versus the control in the phase 3-eligible population, which the company described as a potential double treatment benefit relative to the 15% and 22% reductions reported for currently approved therapies in the US at 12 and 24 months, respectively.
• No OCU410-related serious adverse effects were reported throughout the phase 1 and 2 clinical trials.

Mohamed Genead, MD, chief medical officer of Ocugen, commented, “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. The phase 3 program builds on compelling 12-month phase 2 data, which demonstrated 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."

The RMAT designation granted by the FDA on July 29, 2026, was based on the phase 2 clinical data that showed clinically meaningful efficacy and a favorable safety profile, with no serious adverse events related to OCU410 reported. The RMAT designation is granted to regenerative medicine therapies intended to treat serious or life-threatening conditions where preliminary clinical evidence indicates the potential to address an unmet medical need.

What Is OCU410?

The company described that OCU410 delivers the human retinoid-related orphan receptor alpha modifier gene in one subretinal injection of an adeno-associated virus serotype 5 vector. The design of OCU410 facilitates simultaneous addressing of multiple pathophysiological drivers of GA, ie, complement overactivation, chronic inflammation, oxidative stress, and lipid dysregulation. This activity is in contrast to therapies that address one pathway, according to the press release, and this positions OCU410 as a differentiated approach from approved complement inhibitors in the US, which address individual disease pathways and require ongoing intravitreal injections.

Phase 3 study design

The trial is a global, multicenter, randomized, controlled study conducted at sites in the US, Canada, Europe, and Latin America. The study includes 237 subjects with GA secondary to dAMD. Participants are randomized 2:1 to receive one 200-µL subretinal injection of OCU410 (5×10¹⁰ vg/mL) or an untreated control arm.

The primary endpoint is the rate of change of the square root-transformed GA lesion area (√mm²/year) determined by fundus autofluorescence at baseline and months 4, 8, and 12. The secondary endpoints are the proportion of subjects with a loss of low-luminance visual acuity of 15 or more Early Treatment Diabetes Retinopathy Study letters at two consecutive visits through month 12, providing a functional vision anchor to the primary anatomic endpoint; and the rate of change of the area of ellipsoidal zone loss determined by spectral-domain optical coherence tomography.

Victor Gonzalez, MD, a study investigator, said patients with GA "continue to face irreversible structural and functional loss of the retina, along with limited treatment options. 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 US, which require patients to undergo multiple injections every year."

Phase 2 ArMaDa data

The phase 2 ArMaDa trial (NCT06018558) was a multicenter, randomized, controlled study that included 51 subjects with GA secondary to dAMD.

In addition to the 31% reduction in the rate of GA lesion area growth at 12 months in the medium dose group, representing a potential 2 times treatment benefit relative to the 15% and 22% reductions reported for currently approved therapies in the US at 12 and 24 months, respectively, the study also showed a 27% reduction in ellipsoid zone area loss in the medium dose group versus control, a structural correlate of visual function.

Other findings in the medium dose group were that about 20% of treated subjects had no disease progression and 75% had more than a 30% reduction in lesion growth at 12 months.