Accelerating Alzheimer's therapeutic development: The past and future of clinical trials.

Alzheimer's disease (AD) research has entered a new era with the recent positive phase 3 clinical trials of the anti-Aβ antibodies lecanemab and donanemab. Why did it take 30 years to achieve these successes? Developing potent therapies for reducing fibrillar amyloid was key, as was selection of patients at relatively early stages of disease. Biomarkers of the target pathologies, including amyloid and tau PET, and insights from past trials were also critical to the recent successes. Moving forward, the challenge will be to develop more efficacious therapies with greater efficiency. Novel trial designs, including combination therapies and umbrella and basket protocols, will accelerate clinical development. Better diversity and inclusivity of trial participants are needed, and blood-based biomarkers may help to improve access for medically underserved groups. Incentivizing innovation in both academia and industry through public-private partnerships, collaborative mechanisms, and the creation of new career paths will be critical to build momentum in these exciting times.

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Copyright © 2023 University of California, San Francisco. Published by Elsevier Inc. All rights reserved.

Déclaration de conflit d'intérêts

Declaration of interests Adam Boxer has served as a consultant to AGTC, Alector, Alzprotect, Amylyx, Arkuda, Arrowhead, Arvinas, Aviado, Boehringer Ingelheim, Denali, Eli Lilly, GSK, Humana, Life Edit, Merck, Modalis, Oligomerix, Oscotec, Roche, Transposon and Wave. He has received research support from Biogen and Eisai for serving as a site investigator for clinical trials, as well as from Regeneron. He has received research support from the National Institutes on Aging: NIH U19AG063911, R01AG073482, R56AG075744, R01AG038791, RF1AG077557, R01AG071756, U24AG057437; Rainwater Charitable Foundation, Bluefield Project to Cure FTD, GHR Foundation, Alzheimer’s Association, Association for Frontotemporal Degeneration, Gates Ventures, Alzheimer’s Drug Discovery Foundation, UCSF Parkinson’s Spectrum Disorders Center and the University of California Cures AD Program. Reisa Sperling has served as a consultant to AC Immune, Acumen, Alector, Bristol Myers Squibb, Genentech, Ionis, Janssen, Oligomerix, Prothena, Roche, Shionogi and Vaxxinity. Her spouse has been a consultant to Merck and Novartis. She has received research funding from the National Institute on Aging, NIH: P01AG036694, U24AG057437; R01AG063689; R01AG054029; R01AG061848; Alzheimer’s Association, GHR Foundation, Gates Ventures, an Anonymous Foundation, Accelerating Medicines Partnership FNIH, and public partnership trial funding from Eli Lilly, and Eisai.