Avacincaptad Pegol Slows Progressive Ellipsoid Zone Degradation/Loss in Eyes With Geographic Atrophy.

Abstract

Ellipsoid zone (EZ) integrity as measured by spectral-domain optical coherence tomography (SD-OCT) is a key biomarker and surrogate for photoreceptor health, including in age-related macular degeneration (AMD). The objectives of this study were to determine (1) the association of baseline EZ measures with geographic atrophy (GA) progression and photoreceptor loss, and (2) the impact of avacincaptad pegol (ACP), a complement inhibitor, on EZ integrity over the first year of treatment. Post hoc analysis of pooled data from the phase 2/3 GATHER1 and phase 3 GATHER2 trials. Patients ≥50 years of age with non‒center point involving GA in the study eye. SD-OCT images were evaluated using advanced multilayer segmentation with certified reader validation for EZ integrity, measuring total EZ attenuation or loss (EZ to retinal pigment epithelium [RPE] thickness of 0 μm; i.e., total loss of EZ) and partial EZ attenuation or degradation (EZ-RPE thickness of ≤20 μm). GA lesion growth was assessed through fundus autofluorescence. (1) Natural history assessment of progression of GA and total EZ attenuation in sham-treated eyes based on quartiles of baseline EZ measures, and (2) the impact of ACP treatment vs sham on progression of total and partial EZ attenuation over 12 months were evaluated. This study included 292 ACP 2 mg and 332 sham eyes. In sham-treated eyes, mean GA growth and progression of total EZ attenuation were substantially greater in higher quartiles of baseline total EZ attenuation and partial EZ attenuation measures over 12 months. ACP 2 mg significantly reduced mean growth in total EZ attenuation by 19.5% (P=0.0009) and mean growth in percentage of partial EZ attenuation by 55.3% (P<0.0001) vs sham over 12 months. Greater baseline total and partial EZ attenuation were associated with higher rates of GA lesion growth and progressive EZ loss over time, establishing these EZ measures as important predictors of future GA growth and photoreceptor loss. Treatment with ACP reduced EZ loss and degradation over 12 months vs sham. EZ measures may enhance identification of patients at high risk of disease progression who would benefit from early therapeutic intervention.