Modeling amyloid plaque turnover dynamics improves characterization of drug effects.

ABSTRACT:

Introduction

Effect on amyloid plaque as measured by positron emission tomography imaging with Centiloid standardization of two therapeutic approaches targeting amyloid beta (Aβ) was investigated using exposure-response modeling.

Methods

Individual-level verubecestat data from the APECS trial were pooled with summary-level data from the literature for amyloid monoclonal antibodies (mAbs) and fitted in a joint non-linear mixed-effects model.

Results

An indirect-response (turnover) model with verubecestat inhibiting plaque formation and mAbs stimulating plaque removal well represented the data. The estimated plaque elimination half-life was 6.4 years. Daily verubecestat 40 mg was estimated to reduce formation by 91.8%. Aducanumab 10 mg/kg every 4 weeks (Q4W), donanemab

SUBMITTER: van Maanen E 

PROVIDER: S-EPMC12639402 | biostudies-literature | 2025 Oct-Dec

REPOSITORIES: biostudies-literature