Key considerations for combination therapy in Alzheimer's clinical trials: Perspectives from an expert advisory board convened by the Alzheimer's drug discovery foundation - 11/01/25

Doi : 10.1016/j.tjpad.2024.100001

Jeffrey Cummings ^a, Michael Gold ^b, Mark Mintun ^c, Michael Irizarry ^d, Andrew von Eschenbach ^e, Suzanne Hendrix ^f, Donald Berry ^g, Cristina Sampaio ^h, Kaycee Sink ⁱ, Jaren Landen ^j, Miia Kivipelto ^k, Michael Grundman ^l, Steven E. Arnold ^m, Allan Green ⁿ, Katherine Partrick ^o, Laura Nisenbaum ^p, Aaron Burstein ^p, Howard Fillit ^p,^⁎
^a Chambers-Grundy Center for Transformative Neuroscience, Department of Brain Health, School of Integrated Health Sciences, University of Nevada, Las Vegas, Las Vegas, NV, USA
^b Compass Pathways, London, UK
^c Eli Lilly and Company, Indianapolis, IN, USA
^d Eisai Inc, Nutley, NJ, USA
^e Samaritan Health Initiatives, Houston, TX, USA
^f Pentara Corporation, Millcreek, UT, USA
^g Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, TX, USA, Berry Consultants, LLC, Austin TX, USA
^h CHDI Management, Inc. the company that manages the scientific activities of CHDI Foundation Princeton, NJ, USA, Faculdade Medicina University of Lisbon, Lisboa, Portugal
ⁱ Genentech Inc., South San Francisco, CA, USA
^j Biogen, Cambridge, MA, USA at the time of advisory board
^k Department of Neurobiology, Care Sciences and Society, Center for Alzheimer Research, Karolinska Institutet, Stockholm, Sweden, Ageing Epidemiology Research Unit (AGE), School of Public Health, Faculty of Medicine, Imperial College London, UK, Institute of Public Health and Clinical Nutrition, University of Eastern Finland, Kuopio, Finland
^l Global R&D Partners, LLC., San Diego, CA, USA and University of California, San Diego, San Diego, CA, USA
^m Department of Neurology, Harvard Medical School, Massachusetts General Hospital, Boston, MA, USA
ⁿ SDG, LLC, Cambridge, MA, USA
^o Independent Researcher, Albuquerque, NM, USA
^p Alzheimer's Drug Discovery Foundation, New York, NY, USA

^⁎Corresponding author at: Alzheimer's Drug Discovery Foundation, 57 West 57th St. Suite 904, New York, NY 10019, USA.Address: Alzheimer's Drug Discovery Foundation, 57 West 57th St. Suite 904New YorkNY10019USA

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Abstract

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.

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Keywords : Alzheimer's disease, Combination therapy, Clinical trials, Preclinical research, Biomarkers

Plan

Introduction

State of the field

Understanding the landscape for combination therapy & applying lessons from oncology

Regulatory considerations

Key considerations

Key questions

Considerations for the impact of anti-aβ monoclonal antibody therapies on trial design

Key considerations

Key questions

Trial design considerations

Key considerations

Key questions

Statistical considerations

Key questions

Operational and strategic considerations

Key considerations

Key questions

Conclusion

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Vol 12 - N° 1

Article 100001- janvier 2025 Retour au numéro

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Key considerations for combination therapy in Alzheimer's clinical trials: Perspectives from an expert advisory board convened by the Alzheimer's drug discovery foundation - 11/01/25

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