Comparative Efficacy and Safety of Avacincaptad Pegol vs. Pegcetacoplan in Treatment of Geographic Atrophy: Insights From a Multilevel Network Meta-Regression
Author(s)
Jelena Jovanovic, DPhil1, Vagia Daki, MSc2, Georgios Kantidakis, PhD2, Ines Guerra, MSc1, Scott Doyle, PhD3, Maria Mata Lorenzo, MSc3, He Guo, MPP, MSc4.
1IQVIA, London, United Kingdom, 2IQVIA, Athens, Greece, 3Astellas Pharma Europe Ltd., Addlestone, United Kingdom, 4Astellas Pharma Inc., Northbrook, IL, USA.
1IQVIA, London, United Kingdom, 2IQVIA, Athens, Greece, 3Astellas Pharma Europe Ltd., Addlestone, United Kingdom, 4Astellas Pharma Inc., Northbrook, IL, USA.
OBJECTIVES: Avacincaptad pegol (ACP) and pegcetacoplan (PEG) are FDA-approved complement inhibitors for slowing progression of geographic atrophy (GA) but have not been directly compared in a randomized trial. A population-adjusted indirect treatment comparison was conducted to evaluate their relative efficacy and safety.
METHODS: Due to substantial population heterogeneity, a multi-level network meta-regression (ML-NMR) was employed. This method combined individual patient data from the registrational trials for ACP (GATHER1 and GATHER2) with aggregate data from the pivotal PEG trials (FILLY, OAKS, and DERBY) to estimate relative effects in the target populations. Studies were included if they reported outcomes at specified timepoints and had baseline values for key effect modifiers (EMs).
RESULTS: At Month 12, ACP showed numerically greater efficacy than PEG in attenuating GA lesion growth and in slowing the decline in visual acuity under normal luminance or low luminance conditions, although differences were neither statistically nor clinically significant. Efficacy differences at Month 24 were also non-significant and highly uncertain due to shorter duration of the GATHER1 trial. However, the odds of new onset choroidal neovascularization (CNV) in the study eye at Month 24 were significantly lower with ACP compared to PEG dosed every month by 85% [odds ratio (OR), 0.15; 95% credible interval (CrI), 0.04, 0.45] and were also numerically lower compared to PEG dosed every other month though marginally non-significant (OR, 0.32; 95% CrI, 0.09, 1.03).
CONCLUSIONS: ACP was associated with a significantly lower incidence of new onset CNV compared to PEG while maintaining similar efficacy in slowing GA lesion growth and visual acuity loss. The key strength of this analysis is the use of ML-NMR, which leverages all available data to achieve robust population adjustment across all EMs identified through published evidence and/or clinical opinion. These insights help address a critical evidence gap in the evolving treatment paradigm for GA.
METHODS: Due to substantial population heterogeneity, a multi-level network meta-regression (ML-NMR) was employed. This method combined individual patient data from the registrational trials for ACP (GATHER1 and GATHER2) with aggregate data from the pivotal PEG trials (FILLY, OAKS, and DERBY) to estimate relative effects in the target populations. Studies were included if they reported outcomes at specified timepoints and had baseline values for key effect modifiers (EMs).
RESULTS: At Month 12, ACP showed numerically greater efficacy than PEG in attenuating GA lesion growth and in slowing the decline in visual acuity under normal luminance or low luminance conditions, although differences were neither statistically nor clinically significant. Efficacy differences at Month 24 were also non-significant and highly uncertain due to shorter duration of the GATHER1 trial. However, the odds of new onset choroidal neovascularization (CNV) in the study eye at Month 24 were significantly lower with ACP compared to PEG dosed every month by 85% [odds ratio (OR), 0.15; 95% credible interval (CrI), 0.04, 0.45] and were also numerically lower compared to PEG dosed every other month though marginally non-significant (OR, 0.32; 95% CrI, 0.09, 1.03).
CONCLUSIONS: ACP was associated with a significantly lower incidence of new onset CNV compared to PEG while maintaining similar efficacy in slowing GA lesion growth and visual acuity loss. The key strength of this analysis is the use of ML-NMR, which leverages all available data to achieve robust population adjustment across all EMs identified through published evidence and/or clinical opinion. These insights help address a critical evidence gap in the evolving treatment paradigm for GA.
Conference/Value in Health Info
2025-11, ISPOR Europe 2025, Glasgow, Scotland
Value in Health, Volume 28, Issue S2
Code
CO54
Topic
Clinical Outcomes, Study Approaches
Topic Subcategory
Comparative Effectiveness or Efficacy
Disease
Biologics & Biosimilars, Geriatrics, Sensory System Disorders (Ear, Eye, Dental, Skin)