ASRS 2026: Pegcetacoplan shows greater treatment effect in eyes with GA and concurrent neovascular AMD

Background

Pegcetacoplan (Syfovre; Apellis Pharmaceuticals) reduced progression of geographic atrophy (GA) in 2 phase 3 clinical trials, but those trials excluded patients who had GA with concurrent neovascular age-related macular degeneration (nAMD) at baseline. In routine clinical practice, however, many eyes with GA also have nAMD. Hasenin Al-khersan, MD, of Retina Group of Florida, presented real-world data addressing this gap at the American Society of Retina Specialists (ASRS) 2026 annual meeting in Montreal, Canada.

Study design

Al-khersan and colleagues retrospectively analyzed data from the Retina Consultants of America (RCA) network, using RetinAI Discovery, a CE-marked artificial intelligence (AI) platform, to segment photoreceptor (PR) and retinal pigment epithelium (RPE) loss on optical coherence tomography (OCT) images (Heidelberg Spectralis). Eligible eyes had at least 12 months of natural history data before pegcetacoplan initiation and at least 12 months of treatment, including 5 or more injections, afterward. GA with concurrent nAMD was defined as at least 1 anti-VEGF injection during the natural history period.

The natural history analysis included 497 eyes from 375 patients (GA only, 240 eyes; GA with nAMD, 257 eyes). The treatment-phase analysis included 240 eyes from 199 patients (GA only, 98 eyes; GA with nAMD, 142 eyes). Pegcetacoplan was administered approximately every 6.1 weeks; eyes with concurrent nAMD received anti–VEGF injections at a mean interval of 5.7 weeks.

Key findings

Before treatment, PR and RPE loss rates were numerically similar between the GA-only and GA-with-nAMD cohorts, reaching statistical significance only for PR loss rate (1.79 mm²/year vs 1.55 mm²/year; P =.026); RPE loss rates were 1.49 mm²/year and 1.35 mm²/year, respectively (P =.125).

After pegcetacoplan initiation, both cohorts showed statistically significant reductions in loss rates. In the GA-only cohort, PR loss rate decreased 41% and RPE loss rate decreased 23% (P <.001 for both), delaying projected progression by approximately 5 months for PR and 2.8 months for RPE. In the GA-with-nAMD cohort, PR loss rate decreased 58% and RPE loss rate decreased approximately 40% (P <.001 for both), delaying projected progression by approximately 7 months for PR and 4.8 months for RPE—a numerically larger treatment effect than in the GA-only cohort.

"This is important because it’s really a cohort of patients that were not evaluated in the clinical trial," Al-khersan said. Visual acuity and intraocular pressure were comparable between cohorts at baseline.

Clinical significance

Al-khersan noted that eyes with GA and concurrent nAMD have historically been difficult to evaluate because confounding OCT features can affect geographic atrophy measurement. Improvements in AI-based segmentation, paired with manual and automated quality control, helped address those confounders in this analysis.

The findings suggest pegcetacoplan is effective in eyes with GA and concurrent nAMD, and potentially more effective than in eyes with GA alone—a distinction with direct clinical relevance given the substantial overlap between the 2 diseases in practice. Al-khersan said the results may help clinicians counsel patients with combined disease about expected treatment response, though he noted further study is needed to understand the mechanism behind the larger observed effect.

Reference:

1. Al-khersan H. Assessment of geographic atrophy progression following pegcetacoplan in the real world with and without neovascular age-related macular degeneration. Presented at: American Society of Retina Specialists (ASRS) 44th Annual Meeting; July 15-18, 2026; Montreal, Canada.