Dilsher S. Dhoot, MD, FASRS, on the landscape of geographic atrophy therapy

Dilsher S. Dhoot, MD, FASRS, provided an update on the current treatment landscape for geographic atrophy (GA) in a recent interview with the Eye Care Network. “Geographic atrophy causes progressive and irreversible vision loss,” he noted, emphasizing the clinical urgency given that the median time to foveal involvement is approximately 2.5 years from diagnosis.

Dhoot is a retina specialist with California Retina Consultants and an adjunct clinical assistant professor of ophthalmology at the Keck School of Medicine at the University of Southern California in Los Angeles.

The year 2023 marked a significant shift with the FDA approvals of pegcetacoplan, a complement C3 inhibitor, and avacincaptad pegol (ACP), a complement C5 inhibitor. Both therapies target dysregulation in the innate immune system’s complement pathway, with the aim of slowing GA lesion progression. “We’re regulating complement and thereby allowing these GA lesions to grow slower,” he said.

Dhoot reviewed key data from the pegcetacoplan program, including the OAKS and DERBY phase 3 trials and the GALE open-label extension. Over 48 months, pegcetacoplan showed increasing benefit: “We saw in the last 24 months... a 28% reduction in GA growth,” compared with 19% to 18% in the initial 24 months. The most notable tissue preservation occurred in nonsubfoveal lesions, with up to 3.16 mm² of preserved area by month 48.

ACP’s efficacy was demonstrated in the GATHER 1 and 2 trials, which enrolled only nonsubfoveal patients. “We see again a reduction in the growth of the GA lesions,” Dhoot said, highlighting a 35.4% reduction in GATHER 1 and 17.7% in GATHER 2 at 12 months.

Safety profiles were generally favorable, he noted. Pegcetacoplan has a low incidence of injection-related vasculitis (1 in 4000), and both agents show a dose-dependent risk of choroidal neovascularization.

Dhoot emphasized patient education: “These drugs don’t improve vision… They just slow them down.” He also noted the need for more durable and effective therapies, adding, “We’re just at the beginning of the evolution of GA treatment.”

Reference

1. Dhoot D. Update on current treatments for geographic atrophy. Presented at: Sonoma Eye 2025 Meeting; March 20-23, 2025; San Diego, CA.