Disease Modeling and Model-Based Meta-Analyses to Define a New Direction for a Phase III Program of Gantenerumab in Alzheimer's Disease.

ABSTRACT: Selecting the right dose is a significant challenge in designing clinical development programs, especially for slowly progressing diseases lacking predictive biomarkers of efficacy that may require long-term treatment to assess clinical benefit. Gantenerumab, a fully human monoclonal antibody (mAb) that binds to aggregated amyloid-beta, was tested in two 24-month phase III studies (NCT01224106, NCT02051608) in participants with prodromal and mild Alzheimer's disease (AD), respectively. Dosing in the first phase III study was suspended after a preplanned interim futility analysis in 2014. Subsequently, a dose-response relationship was observed in a subgroup of fast AD progressors that, together with contemporary aducanumab (another anti-amyloid-beta mAb) data, indicated higher doses may be

SUBMITTER: Retout S 

PROVIDER: S-EPMC9313867 | biostudies-literature | 2022 Apr

REPOSITORIES: biostudies-literature