Pegcetacoplan delays time to development of central scotoma loss of central macular sensitivity: a microperimetry analysis of the phase 3 OAKS study

Abstract

Purpose : To report the effect of pegcetacoplan monthly (PM) and every other month (PEOM) vs sham in delaying occurrence of absolute scotoma of the central macular 4 and 16 loci of the Macular Integrity Assessment (MAIA) microperimetry grid in the phase 3 OAKS study.

Methods : Patients were randomized to receive intravitreal PM, PEOM or sham injections for 24 months. Absolute scotomas were defined as absence of patient response to the brightest stimuli (0 dB) and denoted as -1 dB. For time-to-event analysis, the events of interest were development of absolute scotomas occurring at all central macular 4 and 16 loci, respectively. Events were depicted via Kaplan-Meier plots. Cox proportional hazards models were applied to estimate hazard ratios (HRs).

Results : 637 patients (PM: n=213; PEOM: n=212; sham pooled: n=212) enrolled in OAKS. For analysis of the central 4 macular loci, 18.3% of patients at baseline had absolute macular scotoma at the central 4 loci and were excluded. For the remaining patients, 34.9% had 2 or 3 and 46.8% had ≤1 central macular scotomatous loci at baseline microperimetry assessment (mean normal-luminance best-corrected visual acuity: 56.8 and 65.3 letters, respectively). 453 patients (PM: n=155; PEOM: n=152; sham pooled: n=146) with ≤3 central macular scotomatous loci at baseline and a post-baseline microperimetry assessment were included in the time-to-event analysis. Conversion of all 4 central macular loci to absolute scotomas occurred in 54 (34.8%), 59 (38.8%), and 64 (43.8%) patients in the PM, PEOM, and sham pooled arms, respectively. PM and PEOM significantly delayed occurrence of absolute scotomas vs sham in the central macular 4 loci (PM: HR vs sham: 0.66 [34% risk reduction]; 95% confidence interval [CI]: 0.46, 0.96; p=0.0282; PEOM: HR vs sham: 0.64 [36% risk reduction]; 95% CI: 0.45, 0.92; p=0.0164) and in a second analysis of 16 loci (PM: HR vs sham: 0.57 [43% risk reduction]; 95% CI: 0.33, 0.96; p=0.0361; PEOM: HR vs sham: 0.52 [48% risk reduction]; 95% CI: 0.32, 0.85; p=0.0084).

Conclusions : 24-month OAKS data demonstrate significant functional benefit of pegcetacoplan to delay onset of central absolute scotoma, supporting a treatment effect of pegcetacoplan on maintaining central macular functionality in patients with GA.

This abstract was presented at the 2024 ARVO Annual Meeting, held in Seattle, WA, May 5-9, 2024.