Key considerations for combination therapy in Alzheimer's clinical trials: Perspectives from an expert advisory board convened by the Alzheimer's drug discovery foundation
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.
Authors
- Cristina Sampaio (ORCID: https://orcid.org/0000-0002-7052-9079)
- Suzanne Hendrix (ORCID: https://orcid.org/0000-0002-2374-7727)
- Kaycee M. Sink (ORCID: https://orcid.org/0000-0001-9608-3856)
- Howard Fillit (ORCID: https://orcid.org/0000-0002-3310-0492)
- Mark Mintun
- Jaren W. Landen
- Michael Gold (ORCID: https://orcid.org/0000-0002-4410-1669)
- Aaron H. Burstein (ORCID: https://orcid.org/0009-0008-0176-9184)
- Jeffrey Cummings
- Steven Edward Arnold (ORCID: https://orcid.org/0000-0002-9487-415X)
- Katherine Partrick
- Michael Grundman
- Miia Kivipelto (ORCID: https://orcid.org/0009-0001-1069-1787)
- Allan Green (ORCID: https://orcid.org/0000-0002-4156-9207)
- Michael C. Irizarry (ORCID: https://orcid.org/0000-0002-0246-2511)
- Donald Berry
- Laura Nisenbaum
- Andrew von Eschenbach
Institutions
- Biogen (United States) (US)
- University of Nevada, Las Vegas (US)
- Alzheimer's Drug Discovery Foundation (US)
- The University of Texas MD Anderson Cancer Center (US)
- Harvard University (US)
- University of San Diego (US)
- Eli Lilly (United States) (US)
- University of Eastern Finland (FI)
- CHDI Foundation (US)
- Advisory Board Company (United States) (US)
- Massachusetts General Hospital (US)
- Pathways Behavioral Services (US)
- Community Initiatives (US)
- Eisai (United States) (US)
- TetraLogic Pharmaceuticals (United States) (US)
Publication Details
- Journal
- The Journal of Prevention of Alzheimer s Disease
- Published
- 2025-01-01
- DOI
- https://doi.org/10.1016/j.tjpad.2024.100001
- Citations
- 12
- Primary Topic
- Health Systems, Economic Evaluations, Quality of Life
- Type
- article
- Field-Weighted Citation Impact
- 37.57