Progression to complete retinal pigment epithelium and outer retinal atrophy (cRORA): post hoc analysis of the GATHER1 trial

Abstract Purpose Determine rates of progression of incomplete retinal pigment epithelium and outer retinal atrophy (iRORA) to complete retinal pigment epithelium and outer retinal atrophy (cRORA) and rates of progression of drusen to iRORA/cRORA in eyes with geographic atrophy (GA) treated with avacincaptad pegol (ACP). Methods Post hoc analysis of the GATHER1 prospective, randomized, double-masked Phase II/III study that evaluated ACP 2 mg vs. sham. Optical coherence tomography (OCT) data from GATHER1 were transferred to the Doheny Image Reading and Research Lab for masked analysis by readers experienced with Classification of Atrophy Meeting (CAM) grading features. Regions of OCT volume scans more than 500 µm from the border of GA lesions were evaluated at baseline and at months 6, 12, and 18. Participants with iRORA and/or drusen (≥ 40 µm height on OCT) at baseline were included in the analysis. Results The proportion of eyes progressing from iRORA to cRORA in the ACP 2 mg group was 5.0%, 15.0%, and 20.0% at months 6, 12, and 18 respectively, as compared with 11.8%, 30.2%, and 41.8% of eyes in the sham group. The proportion of ACP 2 mg-treated eyes progressing from drusen to iRORA or cRORA was 3.8%, 7.6%, and 7.6% at months 6, 12, and 18 compared with 15.9%, 18.1%, and 27.2% of sham-treated eyes. Conclusions Rates of progression from iRORA to cRORA and drusen to iRORA/cRORA were reduced in eyes treated with ACP 2 mg vs. sham, with increasing separation between groups over time, suggesting early intervention may slow disease progression. Trial registration ClinicalTrials.gov identifier: NCT02686658. Date of registration: February 16, 2016. Key messages What is known Geographic atrophy is an advanced form of age-related macular degeneration (AMD) that leads to irreversible vision loss, presenting a significant public health unmet need. The Classification of Atrophy Meeting (CAM) group recommended a new nomenclature for advanced AMD lesions, based on the affected anatomical layers on optical coherence tomography. Accordingly, the terms incomplete retinal pigment epithelium and outer retinal atrophy (iRORA) and complete retinal pigment epithelium and outer retinal atrophy (cRORA) were introduced (Guymer et al., Ophthalmology 127:394–409, 2020; Sadda et al., Ophthalmology 125:537–548, 2018). What is new GATHER1 post hoc analysis shows that treatment with avacincaptad pegol (ACP) 2 mg decreases the proportion of eyes that progress from iRORA to cRORA, and from drusen to iRORA or cRORA, compared with sham, over 6, 12, and 18 months. These findings suggest a potential role for ACP in delaying the progression of existing pre-atrophic AMD lesions