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

 Sabahat Iqbal, Cristina Bonet Olivares, Laura Rizzo, Thomas D. Parker, Charis Wong, Benjamin R. Underwood, James Carpenter, Ross Dunne, Vanessa Raymont … See all authors 

https://doi.org/10.1002/alz.71495

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 for Health and Care Research (NIHR), we developed a systematic drug prioritization 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 standardized 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 prioritization pipeline will speed the identification and progression of promising candidates for therapeutic evaluation.

Highlights

• Repurposed drug identification for Alzheimer's disease (AD) platform trials.
• Drug discovery strategy for an adaptive platform trial in AD.
• Integration of machine learning for repurposed drug compound selection.
• Pragmatic drug selection based on efficacy, safety, and trial feasibility.

Funding information:

This study was supported by the UK National Institute for Health and Care Research (NIHR) under the Application Development Award scheme (NIHR165710). The funding body had no role in the development of the drug prioritization pipeline or manuscript preparation.

https://alz-journals.onlinelibrary.wiley.com/doi/10.1002/alz.71495