Pegcetacoplan Treatment and Consensus Features of Geographic Atrophy Over 24 Months.

IMPORTANCE: Despite widespread availability and consensus on its advantages for detailed imaging of geographic atrophy (GA), spectral-domain optical coherence tomography (SD-OCT) might benefit from automated quantitative OCT analyses in GA diagnosis, monitoring, and reporting of its landmark clinical trials.

OBJECTIVE: To analyze the association between pegcetacoplan and consensus GA SD-OCT end points.

DESIGN, SETTING, AND PARTICIPANTS: This was a post hoc analysis of 11 614 SD-OCT volumes from 936 of the 1258 participants in 2 parallel phase 3 studies, the Study to Compare the Efficacy and Safety of Intravitreal APL-2 Therapy With Sham Injections in Patients With Geographic Atrophy (GA) Secondary to Age-Related Macular Degeneration (OAKS) and Study to Compare the Efficacy and Safety of Intravitreal APL-2 Therapy With Sham Injections in Patients With Geographic Atrophy (GA) Secondary to Age-Related Macular Degeneration (DERBY). OAKS and DERBY were 24-month, multicenter, randomized, double-masked, sham-controlled studies conducted from August 2018 to July 2020 among adults with GA with total area 2.5 to 17.5 mm2 on fundus autofluorescence imaging (if multifocal, at least 1 lesion ≥1.25 mm2). This analysis was conducted from September to December 2023.

INTERVENTIONS: Study participants received pegcetacoplan, 15 mg per 0.1-mL intravitreal injection, monthly or every other month, or sham injection monthly or every other month.

MAIN OUTCOMES AND MEASURES: The primary end point was the least squares mean change from baseline in area of retinal pigment epithelium and outer retinal atrophy in each of the 3 treatment arms (pegcetacoplan monthly, pegcetacoplan every other month, and pooled sham [sham monthly and sham every other month]) at 24 months. Feature-specific area analysis was conducted by Early Treatment Diabetic Retinopathy Study (ETDRS) regions of interest (ie, foveal, parafoveal, and perifoveal).

RESULTS: Among 936 participants, the mean (SD) age was 78.5 (7.22) years, and 570 participants (60.9%) were female. Pegcetacoplan, but not sham treatment, was associated with reduced growth rates of SD-OCT biomarkers for GA for up to 24 months. Reductions vs sham in least squares mean (SE) change from baseline of retinal pigment epithelium and outer retinal atrophy area were detectable at every time point from 3 through 24 months (least squares mean difference vs pooled sham at month 24, pegcetacoplan monthly: -0.86 mm2; 95% CI, -1.15 to -0.57; P < .001; pegcetacoplan every other month: -0.69 mm2; 95% CI, -0.98 to -0.39; P < .001). This association was more pronounced with more frequent dosing (pegcetacoplan monthly vs pegcetacoplan every other month at month 24: -0.17 mm2; 95% CI, -0.43 to 0.08; P = .17). Stronger associations were observed in the parafoveal and perifoveal regions for both pegcetacoplan monthly and pegcetacoplan every other month.

CONCLUSIONS AND RELEVANCE: These findings offer additional insight into the potential effects of pegcetacoplan on the development of GA, including potential effects on the retinal pigment epithelium and photoreceptors.

TRIAL REGISTRATION: ClinicalTrials.gov Identifiers: NCT03525600 and NCT03525613.