Abstract
In randomized clinical trials (RCTs) for Alzheimer’s Disease (AD), cerebrospinal fluid (CSF) and positron emission tomography (PET) biomarkers are currently used for the detection and monitoring of AD pathological features. The use of less resource-intensive plasma biomarkers could decrease the burden to study volunteers and limit costs and time for study enrollment. Blood-based markers (BBMs) could thus play an important role in improving the design and the conduct of RCTs on AD. It remains to be determined if the data available on BBMs are strong enough to replace CSF and PET biomarkers as entry criteria and monitoring tools in RCTs.
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The Task Force was partially funded by registration fees from industrial participants. These corporations placed no restrictions on this work. D. Angioni is an investigator in clinical trials sponsored by Roche, Alector, Janssen, Alzheon, Otsuka, Novo Nordisk, UCB Pharma, Medesis Pharma Eisai, Biogen and the CHU of Toulouse. No direct personal benefit is to be declared. O. Hansson has acquired research support (for the institution) from ADx, AVID Radiopharmaceuticals, Biogen, Eli Lilly, Eisai, Fujirebio, GE Healthcare, Pfizer, and Roche. In the past 2 years, he has received consultancy/speaker fees from AC Immune, Amylyx, Alzpath, BioArctic, Biogen, Cerveau, Eisai, Eli Lilly, Fujirebio, Genentech, Merck, Novartis, Novo Nordisk, Roche, Sanofi and Siemens. R. Bateman Washington University and Randall Bateman have equity ownership interest in C2N Diagnostics and Randall Bateman receives income from C2N Diagnostics for serving on the scientific advisory board. Randall Bateman may receive income based on technology licensed by Washington University to C2N Diagnostics. Randall Bateman has received research funding from Avid Radiopharmaceuticals, Janssen, Roche/Genentech, Eli Lilly, Eisai, Biogen, AbbVie, Bristol Myers Squibb and Novartis. Randall Bateman serves on the Roche Gantenerumab Steering Committee as an unpaid member. C. Rabe is a full-time employee of Genentech and owns stock options in F.Hoffmann-LaRoche. M. Toloue is an employee and shareholder in Quanterix Corporation. J.B. Braunstein is a full-time employee of and owns equity in C2N Diagnostics. Sam Agus is an employee of Diadem spA. J.R. Sims is an employee of Eli Lilly and Company: salary and minor stockholder. T. Bittner is a full-time employee of F.Hoffmann-LaRoche and Genentech and owns stock options in F.Hoffmann-LaRoche. M. Carrillo is a full-time employee of the Alzheimer’s Association. She received lead grants (without funding) from NIA LEADS (Co-PI, non salaried). She has served on the scientific advisory board for San Antonio Alz Center EAB, ATRI/ACTC EAB and US POINTER Study DSM. She has a daughter that is a full-time graduate student in the USC Neuroscience program. H. Fillit received royalties from the Icahn School of Medicine at Mount Sinai. He is an unpaid consultant to Biogen. He has received consulting fees from Alector, Otsuka/Lundbeck, and LifeWork. He owns stock options in eFamilyCare. C.L. Master has nothing to declare. S. Salloway was the co-chair of the Investigator Steering Committee for the Aducanumab phase 3 program and he served as a site PI for the aducanumab and lecanemab phase 3 studies, the donanemab phase 2 trial and he was the Project Arm Leader for gantenerumab in DIAN-TU. He has received consulting income from Biogen, Lilly, Roche, Genentech, Bolden, Amylyx, Prothena and Eisai. He has no stock or royalties related to any medication in development. S. Salloway serves on the planning committee for the National Disease Modifying Treatment and Diagnostic Registry Work Group and he is a member of the ADRD Therapeutics Work Group. He is the first author for the report of ARIA in aducanumab phase 3 (Salloway, JAMA Neurology, 2022), the report of gantenerumab and solanezumab in DIAN-TU (Salloway, Nature Medicine, 2021). He is a co-author on the report of the donanemab phase 2 trial (Mintun, NEJM, 2021) and the Aducanumab Appropriate Use Recommendations (Cummings, Journal of the Prevention of Alzheimer’s Disease, 2021). P. Aisen reports collaborations on the development of blood-based markers with C2N, Janssen and Roche, during the conduct of the study; grants from Lilly, Eisai, NIH, Alzheimer’s Association; consultant fees from Merck, Biogen, Abbvie, Genentech, ImmunoBrain Checkpoint, Arrowhead, outside the submitted work. M. Weiner reports, outside the submitted work, grants from National Institutes of Health (NIH)/NINDS/National Institute on Aging (NIA), Department of Defense (DOD), California Department of Public Health (CDPH), University of Michigan, Siemens, Biogen, Hillblom Foundation, Alzheimer’s Association, Johnson & Johnson, Kevin and Connie Shanahan, GE, VUmc, Australian Catholic University, The Stroke Foundation, Veterans Administration; personal fees from Boxer Capital, Cerecin, Clario, Dementia Society of Japan, Eisai, Guidepoint, Health and Wellness Partners, Indiana University, LCN Consulting, Merck Sharp & Dohme Corp., NC Registry for Brain Health, Prova Education, T3D Therapeutics, University of Southern California (USC), WebMD, from China Association for Alzheimer’s Disease (CAAD), Taipei Medical University, AD/PD Congress, Cleveland Clinic, CTAD Congress, Foundation of Learning, Health Society (Japan), INSPIRE Project; U. Toulouse, Japan Society for Dementia Research, Korean Dementia Society, National Center for Geriatrics and Gerontology (NCGG; Japan), University of Southern California (USC); owns stock-options in Alzeca, Alzheon, ALZ Path, Anven. B Vellas is an investigator in clinical trials sponsored by Biogen, Lilly, Roche, Eisai, Pfizer, Pierre Fabre Pharmaceuticals and the Toulouse University Hospital. He has served as SAB member for Biogen, Alzheon, Green Valley, Norvo Nordisk, Longeveron, Rejuvenate Biomed Clinical Pfizer, Eisai France, Advisory Board Meeting - but received no personal compensation. He has served as consultant and/or SAB member for Roche, Lilly, Eisai, TauX, Cerecin with personal compensation. S. Gauthier is a member of scientific advisory boards of Alzheon, AmyriAD, Biogen Canada, Eisai Canada, Enigma, Lily, Medesis, Roche Canada.
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Angioni, D., Hansson, O., Bateman, R.J. et al. Can We Use Blood Biomarkers as Entry Criteria and for Monitoring Drug Treatment Effects in Clinical Trials? A Report from the EU/US CTAD Task Force. J Prev Alzheimers Dis 10, 418–425 (2023). https://doi.org/10.14283/jpad.2023.68
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DOI: https://doi.org/10.14283/jpad.2023.68