Repurposed drug prioritisation pipeline for a multi-arm platform trial in clinical Alzheimer's disease

Abstract

Introduction: There is an urgent need to identify effective, safe, and affordable treatments for Alzheimer’s disease (AD). Funded by the UK National Institute of Health and Care Research (NIHR), we developed a systematic drug prioritisation pipeline to identify repurposed drug candidates for inclusion in a planned platform trial for clinical AD. Methods: The wider AD community was invited to propose compounds using a standardised proposal template. Fourteen proposals were presented to an international expert panel, who independently ranked compounds based on biological plausibility, preclinical efficacy, safety, and trial feasibility. Extended drug summaries were compiled for shortlisted compounds, supported by ReLiSyR, a machine learning–supported systematic review tool. Results: Following review in a second panel meeting, independent re-ranking identified the following compounds: atomoxetine (1st), metformin (2nd), isosorbide mononitrate and levetiracetam (joint 3rd). Discussion: This robust drug prioritisation pipeline will speed the identification and progression of promising candidates for therapeutic evaluation.