Retina Society 2026: Medium-dose OCU410 gene therapy cuts geographic atrophy progression by up to 32% in phase 2 trial

One subretinal injection of medium-dose OCU410, an investigational adeno-associated virus-5-(AAV5)-based gene therapy, reduced the growth of geographic atrophy (GA) lesions by up to 32% compared with untreated controls at 12 months, according to randomized phase 2 results from the national ArMaDa trial (NCT07770828). The therapy was well tolerated, with no drug-related serious adverse events reported. Raj K. Maturi, MD, and colleagues presented their findings at the Retina Society 2026 annual meeting in Los Angeles, September 23–26. Maturi is from Retina Partners Midwest in Indianapolis.

By the numbers: a third less progression of GA

The ArMaDa trial is a multicenter, open-label, randomized phase 1/2 trial conducted to evaluate OCU410, which encodes the human retinoic acid receptor-related orphan receptor A, in patients with GA secondary to dry age-related macular degeneration (AMD). In the phase 2 segment of the study, 51 subjects were randomized 1:1:1 to treatment with medium-dose OCU410, high-dose OCU410, or untreated control. Of those, 45 could be evaluated at month 12; 16 had received a medium dose, 16 a high dose, and 13 served as controls, after four control subjects and one medium-dose subject were excluded from efficacy analyses due to loss to follow-up or insufficient post-baseline data, Maturi recounted.

In the medium-dose group, the investigators reported that the mean GA lesion growth was 1.42 ± 0.28 mm² vs 2.15 ± 0.30 mm² in the control group, which translated to a 34% reduction in growth. The analysis of the change from baseline through month 12 showed that the medium-dose of OCU410 achieved a 32.3% reduction in lesion growth vs controls (nominal p = 0.0353). The high dose did not demonstrate any meaningful benefit.

In an exploratory subgroup that had baseline areas of GA area of ranging from 2.5 to 17.5 mm², that was aligned with the proposed phase 3 eligibility criteria, medium-dose OCU410 (n = 16) decreased the GA progression by 31.5% compared with the corresponding control subset (n = 12; 1.42 ± 0.28 vs 2.06 ± 0.31 mm²; nominal p = 0.0210). This was accompanied by a 27% reduction in loss of the ellipsoid zone, which is a structural marker of the integrity of the outer retina as assessed by spectral-domain optical coherence tomography. No drug-related serious adverse events or adverse events of special interest were reported.

A case for moving forward

Based on these findings, Maturi and colleagues concluded that one subretinal administration of medium-dose OCU410 was well tolerated and resulted in decreased GA progression at 12 months, along with concordant preservation of the outer retinal structure. Based on these randomized phase 2 findings, the authors believe that the results indicate that the medium dose should be evaluated further in a phase 3 trial.

Maturi commented, "A 32% reduction in lesion growth alongside a 27% reduction in ellipsoid zone loss after just one injection, could be a game changer for dry AMD treatment. I'm looking forward to the results of the ongoing phase 3 confirmatory study."