Abstract
Purpose :
To provide insight into the mechanism and outcomes of pegcetacoplan treatment in GA based on phase III trial results. To assess the effect of pegcetacoplan in the changes in the area of RPE and PR loss using deep learning analysis of spectral domain optical coherence tomography (SD-OCT) images in the prospective phase III trials over 2 years of follow-up.
Methods :
Patients with GA secondary to age-related macular degeneration in the OAKS and DERBY phase III trials were treated with intravitreal pegcetacoplan, a complement C3 and C3b inhibitor, or sham. Randomization was performed 2:2:1:1 into pegcetacoplan monthly (PM), pegcetacoplan every other month (PEOM), sham monthly and sham EOM treatment over 2 years. For year 1, SD OCT monitoring was conducted monthly. For year 2, SD OCT monitoring was conducted monthly for PM and sham monthly groups and then, every other month for the PEOM and sham EOM groups. Subsequently, OCT volumes from Spectralis SD-OCT (n=436 patients in OAKS and n=433 patients in DERBY) were processed by deep learning image analyses using validated algorithms based on convolutional neural networks identifying the loss of RPE layer and ellipsoid zone defined as PR layers. Change from baseline through Month 24 in RPE and PR loss was analyzed using mixed models for repeated measures methodology.
Results :
Following 24 months on therapy, RPE and PR degeneration were significantly and consistently reduced in both trials as evaluated by SD-OCT. In OAKS, RPE loss was reduced by 23.9% (p<0.0001) in PM vs. sham pooled and by 21.4% (p<0.0001) in PEOM vs. sham pooled. Importantly, PR loss was reduced in PM vs. sham pooled by 2.7% (p<0.0001) and in PEOM vs. sham pooled by 45.7% (p<0.0001). In DERBY, progression of RPE loss was reduced in PM vs. sham pooled by 28.4% (p<0.0001) and in PEOM vs. sham pooled groups by 21.2% (p=0.0003). PR loss was reduced in PM vs sham pooled by 7.0% (p<0.0001) and in PEOM vs. sham pooled by 45.8% (p<0.0001).
Conclusions :
AI-based OCT analysis can reliably identify and quantify the loss of RPE and PR layers in disease activity and therapeutic response in GA. Reductions in both RPE and PR degeneration were observed after intravitreal pegcetacoplan therapy in the OAKS and DERBY phase III trials providing further insight into the mechanism and outcomes for the potential first therapy in GA.
This abstract was presented at the 2023 ARVO Annual Meeting, held in New Orleans, LA, April 23-27, 2023.