Advancing geographic atrophy care: Long-term data and real-world insights

In this first of a three-part series, Joseph A. Anaya, MD, MBA, and Ashkan M. Abbey, MD, FASRS, FAAO, review recent advances in the management of geographic atrophy (GA). Over the past 2 years, there has been a fundamental shift with the FDA approval of two agents that can consistently slow GA lesion progression: pegcetacoplan (Syfovre; Apellis Pharmaceuticals, Inc) and avacincaptad pegol (Izervay; Astellas Pharma, Inc). Both agents demonstrated slowing of lesion growth in phase 3 randomized clinical trials, and long-term extension data are now available—5 years for pegcetacoplan and 4 years for avacincaptad pegol. Notably, the 5-year GALE extension study for pegcetacoplan reported a cumulative delay in GA progression of approximately 1.5 years compared with modeled natural history. Both agents show an increasing effect over time, with greater slowing of lesion growth during longer treatment periods.

Safety profiles in the long-term trials were generally favorable. Concerns regarding vasculitis with pegcetacoplan appear to be largely limited to first-injection events, occurring in about 1 in 4,000 injections, and were not observed in clinical trial populations, only in real-world settings.

The discussion notes that traditional end points, such as best-corrected visual acuity (BCVA), do not fully capture functional vision in patients with GA. Functional outcomes, including reading ability, low-luminance vision, and microperimetry, provide a more complete assessment. Patients with GA may maintain 20/25 acuity yet struggle with reading independently due to paracentral lesions, impacting reading speed and causing fatigue. Microperimetry data from the GALE study demonstrate a statistically significant reduction in lost retinal sensitivity over 3 years in patients receiving pegcetacoplan compared with sham, highlighting functional benefits beyond BCVA.

Anaya and Abbey note the need for a holistic evaluation of functional vision, including reading performance, low-light vision, and paracentral sensitivity, to better assess the impact of treatment over time and guide patient management in both clinical trials and real-world practice.

Ashkan M. Abbey, MD, FASRS, FAAO, is in practice at Texas Retina Associates in Dallas, Texas, and director of clinical research. He is a speaker and consultant for Apellis Pharmaceuticals, Inc and Astellas Pharma Inc.

Joseph A. Anaya, MD, MBA, is assistant professor of ophthalmology at Wilmer Eye Institute at Johns Hopkins University School of Medicine in Baltimore, Maryland. He has no relevant financial disclosures.