Emerging therapies for geographic atrophy

Abstract

Geographic atrophy (GA) is a late‐stage form of age‐related macular degeneration (AMD) characterized by progressive degeneration of photoreceptors, retinal pigment epithelium (RPE), and choriocapillaris primarily in the macula. It was shown in AREDS studies that supplementation of high‐dose antioxidant vitamins (C, E, and beta‐carotene) and zinc, decrease the risk of progression to advanced AMD.It was suggested that the complement system, a part of the human immune system, plays an important role in the GA pathophysiology. Different complement genes have been linked to AMD in genome‐wide association studies, and the odds of GA were estimated to be 2.5 times higher per copy of a common risk allele (Y402H) of the CFH gene in individuals of European ancestry. In histologic studies complement proteins were found in drusen as well as elevated levels of complement proteins in the outer retinal tissue of postmortem eyes with AMD. Moreover, higher levels of activated complement products in plasma have been found in GA patients. Thus, several treatments targeting the complement system are investigated. The drugs that showed phase 3 efficacy and safety include pegcetacoplan and avacincaptad pegol, which are complement C3 and complement C5 inhibitors, respectively.