Association of Complement C3 Inhibitor Pegcetacoplan with Photoreceptor Degeneration Beyond Areas of Geographic Atrophy

ABSTRACT Preservation of photoreceptors beyond areas of retinal pigment epithelium atrophy is a critical treatment goal in eyes with geographic atrophy (GA) to prevent vision loss. Thus, we assessed the association of treatment with the complement C3 inhibitor pegcetacoplan with optical coherence tomography (OCT)-based photoreceptor laminae thicknesses in this post hoc analysis of the FILLY trial ( NCT02503332 ). Retinal layers in OCT were segmented using a deep-learning-based pipeline and extracted along evenly spaced contour-lines surrounding areas of GA. The primary outcome measure was change from baseline in (standardized) outer nuclear layer (ONL) thickness at the 5.16°-contour-line at month 12. Participants treated with pegcetacoplan monthly had a thicker ONL along the 5.16° contour-line compared to the pooled sham arm (mean difference [95% CI] +0.29 z-score units [0.16, 0.42],P<.001). The same was evident for eyes treated with pegcetacoplan every other month (+0.26 z-score units [0.13, 0.4],P<.001). Additionally, eyes treated with pegcetacoplan exhibited a thicker photoreceptor inner segment layer along the 5.16°-contour-line at month 12. These findings suggest that pegcetacoplan could slow GA progression and lead to a lesser thinning of photoreceptor layers beyond the GA boundary. Future trials in earlier disease stages, i.e., intermediate AMD, aiming to slow photoreceptor degeneration warrant consideration.