C5 inhibitor avacincaptad pegol treatment for geographic atrophy: A comprehensive review

Abstract

Geographic atrophy (GA) remains a leading cause of central vision loss with no known cure. Until recently, there were no approved treatments for GA, often resulting in poor quality of life for affected patients. GA is characterized by atrophic lesions on the retina that may eventually threaten the fovea. Emerging treatments have demonstrated the ability to reduce the rate of lesion growth, potentially preserving visual function. Avacincaptad pegol (ACP; Astellas Pharma Inc), a complement component 5 inhibitor, is an FDA-approved treatment for GA that has been evaluated in numerous clinical trials. Here we review the current clinical trial landscape of ACP, including critical post hoc analyses that suggest ACP may reduce the risk of severe loss among patients with GA.

Keywords: C5 inhibition; age-related macular degeneration (AMD); aptamer; avacincaptad pegol (ACP); complement; geographic atrophy (GA); retinal disease.

Figure 1.

Simplified Diagram of the Complement Pathway. (A) The complement cascade in its uninhibited form. (B) Inhibited at C5 via avacincaptad pegol (ACP) binding.

Figure 2.

GATHER clinical program baseline lesion inclusion and exclusion criteria: (A) and (B) examples of lesions within 1500 microns of, but not involving, the foveal center point. (C) Outside of 1500 microns from the foveal center point. (D) Involving the foveal centerpoint.

Figure 3.

GATHER1 efficacy outcomes for ACP 2-mg cohort compared with sham. Mean change in observed geographic atrophy (GA) area from baseline (A) through 12 months and (B) through 18 months. Least squares (LS) means based on estimates from a mixed-effects repeated measures (MMRM) model on available intention-to-treat (ITT) populations, up to Month 12 data for A and up to 18 month for B.

Figure 4.

GATHER2 efficacy outcomes for ACP 2-mg cohort compared with sham through 12 months. A MMRM was used to assess differences between the treatment groups in the rate of growth of the observed GA area (slope) over 12 months.

Figure 5.

Post hoc analysis of the GATHER clinical program pooled data comparing proportion of patients with BCVA loss between ACP 2-mg and sham for ≥15 letter loss.

Figure 6.

Post hoc analysis of the GATHER clinical program pooled data comparing risk reduction of patients with BCVA loss between ACP 2-mg and sham for ≥15 letter loss.