Key considerations for combination therapy in Alzheimer's clinical trials: Perspectives from an expert advisory board convened by the Alzheimer's drug discovery foundation

作     者：Cummings, Jeffrey Gold, Michael Mintun, Mark Irizarry, Michael von Eschenbach, Andrew Hendrix, Suzanne Berry, Donald Sampaio, Cristina Sink, Kaycee Landen, Jaren Kivipelto, Miia Grundman, Michael Arnold, Steven E. Green, Allan Partrick, Katherine Nisenbaum, Laura Burstein, Aaron Fillit, Howard 

作者机构：Chambers-Grundy Center for Transformative Neuroscience Department of Brain Health School of Integrated Health Sciences University of Nevada Las Vegas NV United States London United Kingdom Eli Lilly and Company Indianapolis IN United States Eisai Inc Nutley NJ United States Samaritan Health Initiatives Houston TX United States Pentara Corporation UT United States Department of Biostatistics University of Texas MD Anderson Cancer Center Berry Consultants LLC Houston TX United States CHDI Management Faculdade Medicina University of Lisbon Lisboa Inc. the company that manages the scientific activities of CHDI Foundation Princeton NJ Portugal Genentech Inc. South San Francisco CA United States Biogen USA at the time of advisory board Cambridge MA United States Department of Neurobiology Care Sciences and Society Center for Alzheimer Research Karolinska Institutet Ageing Epidemiology Research Unit (AGE) School of Public Health Faculty of Medicine Imperial College London Institute of Public Health and Clinical Nutrition University of Eastern Finland Kuopio Stockholm Finland Global R&D Partners LLC. USA and University of California San Diego CA United States Department of Neurology Harvard Medical School Massachusetts General Hospital Boston MA United States LLC Cambridge MA United States Independent Researcher Albuquerque NM United States Alzheimer's Drug Discovery Foundation New York NY USA 

出 版 物：《The journal of prevention of Alzheimer's disease》 (J Prev Alzheimers Dis)

年 卷 期：2025年第12卷第1期

页      面：100001-100001页

主　　题：Alzheimer's disease Biomarkers Clinical trials Combination therapy Preclinical research 

摘      要：There is growing consensus in the Alzheimer s community that combination therapy will be needed to maximize therapeutic benefits through the course of the disease. However, combination therapy raises complex questions and decisions for study sponsors, from preclinical research through clinical trial design to regulatory, statistical, and operational considerations. In January 2024, the Alzheimer s Drug Discovery Foundation convened an expert advisory board to discuss the key considerations in each of these areas. Experts agreed on the need to prioritize a combination therapy approach that encompasses a wide range of targets associated with aging and the underlying biology of Alzheimer s disease. Progress in combination therapy could be accelerated by leveraging preclinical research and Phase 1 and 2A trials to identify the most promising combinations for further development, exploring repurposed agents with available preclinical and clinical data, building collaborations across sectors to support operational challenges, and planning for the likely impact of anti-amyloid beta-protein monoclonal antibody therapies on future clinical trial designs. Copyright © 2024. Published by Elsevier Masson SAS.