Repurposed Drug Prioritisation Pipeline for an Alzheimer’s Disease Multi‐arm Platform Trial
Year: 2025
Type: article
Abstract: BACKGROUND: Despite recent developments in amyloid-clearing therapies for Alzheimer's Disease (AD), there remains a need for more effective, safe treatments. Funded by the UK National Institute of Health and Care Research, our aim was to establish a robust, systematic, and unbiased drug prioritisation pipeline to identify repurposed drugs with the greatest potential for sustained clinical effect in clinical 'real-world' AD (MMSE >17). These would then be considered for inclusion in a planned multi-arm UK platform trial. METHOD: We invited the wider AD community to propose compounds by summarising their rationale and evidence in a prespecified drug proposal form. Fourteen proposals were received, and the drug proposers were invited to the first panel meeting. They presented a pre-clinical data focused rationale for each compound to an international expert panel comprised of AD clinicians, scientists, industry professionals, as well as both charity and patient/public representatives. In the context of a platform trial using prespecified primary outcome of cognition (ADAS-Cog, with neuropsychiatric symptoms and everyday activities as secondary outcomes), the panel ranked their top three compounds based on efficacy, biological plausibility, and safety in AD. Ten compounds were taken forward with two subsequently excluded due to lack of data in humans. We compiled extended drug curriculum vitae (CV) for the eight shortlisted compounds. This incorporated practical clinically relevant information and was supplemented by systematic clinical literature review using Repurposing Living Systematic Review (ReLiSyR), a machine learning tool that searches databases and screens studies to identify relevant publications. RESULT: ). The pivotal determining factors across the top ranked compounds included scientific evidence of plausible mechanistic pathways in AD as well as evidence of substantial clinical data on safety and tolerability. CONCLUSION: We present a practical approach to prioritising repurposed drugs to evaluate in the context of clinical AD. We would like to thank our patient and public contributors and the wider investigator team.
Source: Alzheimer s & Dementia
Authors: Sabahat Iqbal, Cristina Bonet Olivares, Laura Rizzo, Thomas D Parker, Charis Wong, Benjamin R Underwood, James Carpenter, Ross Dunne, Vanessa Raymont, Alastair Reith, Catherine J. Mummery, Eric H Karran, Fiona Ducotterd, Gordon Wilcock, Jeffrey L. Cummings, John T O'Brien, Leah Mursaleen, Lon S. S Schneider, Rik Vandenberghe, Suzanne J Reeves, Paresh Malhotra
Institutions: Imperial College London, University College London, University of Edinburgh, University of Cambridge, Cambridgeshire and Peterborough NHS Foundation Trust, University of Manchester, University of Oxford, Dementias Platform UK, University of Nevada, Las Vegas, Alzheimer’s Research UK, University of Southern California, KU Leuven, Imperial College Healthcare NHS Trust, UK Dementia Research Institute
Language: English
Subfield: Physiology
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
Estimated APC paid: $4,200
OpenAlex ID: W7117327622