Rate of response to treatment in eyes with geographic atrophy treated with Pegcetacoplan in a within-patient comparison using automated AI-based OCT biomarker quantifications in OAKS and DERBY

Abstract

Purpose : To investigate the response to Pegcetacoplan (PEG) treatment in a 24-months, within-patient, fellow eye comparison using patient- and eye-specific AI-based OCT biomarker quantifications in patients with bilateral geographic atrophy (GA) secondary to age-related macular degeneration.

Methods : Study eyes and fellow eyes with GA from two phase III randomized controlled trials (OAKS, NCT03525613 and DERBY, NCT03525600). Study eyes received Monthly (PM) or Every-other-month (PEOM) PEG, or Sham treatment, and fellow eyes did not receive PEG at any time point. Photoreceptor (PR) integrity and retinal pigment epithelium (RPE) loss were quantified with Spectralis OCT using fully automated AI-based algorithms. PR/RPE loss ratios were calculated, compared between within-patient eyes and examined over time. The symmetry between study and fellow eyes were assessed by grouping PR/RPE values into quartiles and comparing distributions.

Results : 897 patients with Spectralis imaging were originally pooled from OAKS and in DERBY. For a direct comparison, the phase III study inclusion/exclusion criteria were applied to both eyes, and 457 patients (914 eyes) were included in this analysis. At baseline mean (± SD) RPE loss area was 7.66 ± 3.25mm² in the study eyes, and 7.43 ± 3.36mm² in the fellow eyes. Baseline PR integrity loss area was larger than RPE loss in all eyes: 12.06 ± 5.72mm² in study eyes and 11.98 ± 5.70mm² in fellow eyes. By month 24 of the study, the PR integrity loss in the study eyes was reduced compared to the fellow eyes by 46.3% in the PM arm and 45.6% in the PEOM arm. For RPE loss, there was a 26.2% and a 15.9% reduction for PM and PEOM respectively. The sham eyes progressed at a nearly identical rate for both PR integrity loss and RPE loss. In total, 56.1% of within-patient eyes fell within the same quartile, 35.2% of eyes were ± 1 quartile, and only 8.7% of eyes were 2+ quartiles different.

Conclusions : Automated quantification of outer retinal layers with advanced OCT-based AI tools enables personalized patient monitoring of disease activity over time. Fellow eyes that exhibit similar characteristics can serve as an appropriate control to monitor treatment efficacy. The PR/RPE loss ratio appears to be symmetric and is an important biomarker for predicting disease progression and treatment response.

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