Avacincaptad pegol: New therapy for geographic atrophy in age-related macular degeneration

Abstract

Geographic atrophy (GA) is still an important global health concern, especially for patients over 50 years, as it represents a late stage of dry age-related macular degeneration (AMD) and accounts for a large portion of permanent central vision loss. The pathogenesis of GA is complex and multifactorial, including oxidative stress, chronic inflammation, abnormalities in the vitamin A visual cycle and progressive disfunction of the retinal pigment epithelium (RPE). The chronic activation of the complement system, particularly the alternative pathway, is fundamental in the degeneration of RPE cells and photoreceptors. In addition, genetic factors, in particular genetic variants of complement regulatory genes, further increase the risk of disease and can accelerate its progression.

Until recently, treatment options were limited to antioxidant supplements based on Age-Related Eye Disease Study (AREDS and AREDS2) recommendations, which demonstrated average effectiveness in slowing disease progression. However, the emergence of medications targeting the complement system marked a turning point. Pegcetacoplan, the C3 inhibitor, and avacincaptad pegol, the C5 inhibitor, have been shown to slow down GA the progression. Although these drugs do not improve visual acuity, they change the natural course of the disease. The difference in the target of the complement cascade may influence the safety of treatment. However, there is still a need for further research to optimize treatment and individualize therapy for patients with GA.