Effects of the active amyloid beta immunotherapy CAD106 on PET measurements of amyloid plaque deposition in cognitively unimpaired APOE ε4 homozygotes
Open accessAbstract
INTRODUCTION: Alzheimer's Prevention Initiative Generation Study 1 evaluated amyloid beta (Aβ) active immunotherapy (vaccine) CAD106 and BACE-1 inhibitor umibecestat in cognitively unimpaired 60- to 75-year-old participants at genetic risk for Alzheimer's disease (AD). The study was reduced in size and terminated early. Results from the CAD106 cohort are presented. METHODS: Sixty-five apolipoprotein E ε4 homozygotes with/without amyloid deposition received intramuscular CAD106 450 μg (n = 42) or placebo (n = 23) at baseline; Weeks 1, 7, 13; and quarterly; 51 of them had follow-up Aβ positron emission tomography (PET) scans at 18 to 24 months. RESULTS: CAD106 induced measurable serum Aβ immunoglobulin G titers in 41/42 participants, slower rates of Aβ plaque accumulation (mean [standard deviation] annualized change from baseline in amyloid PET Centiloid: -0.91[5.65] for CAD106 versus 8.36 [6.68] for placebo; P < 0.001), and three amyloid-related imaging abnormality cases (one symptomatic). DISCUSSION: Despite early termination, these findings support the potential value of conducting larger prevention trials of Aβ active immunotherapies in individuals at risk for AD. HIGHLIGHTS: This was the first amyloid-lowering prevention trial in persons at genetic risk of late-onset Alzheimer's disease (AD). Active immunotherapy targeting amyloid (CAD106) was tested in this prevention trial. CAD106 significantly slowed down amyloid plaque deposition in apolipoprotein E homozygotes. CAD106 was generally safe and well tolerated, with only three amyloid-related imaging abnormality cases (one symptomatic). Such an approach deserves further evaluation in larger AD prevention trials.
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CAD106 is an active Aβ immunotherapy currently undergoing clinical development, involving multiple doses of whole Aβ1-6 peptide linked to ADP-Q carrier, a virus-like particle that generates high-titer anti-Aβ antibodies.
“CAD106, a further active Aβ immunotherapy, is presently undergoing clinical development. It involves administering multiple doses of the whole Aβ1–6 peptide linked to the ADP-Q carrier, a virus-like particle that generates high-titer anti-Aβ antibodies [140,141,153,154].”
From Recent Advances in Therapeutics for the Treatment of Alzheimer’s Disease (2024) · cites this paper as [153]
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- Authors
- Riviere, M., Langbaum, J. B., Turner, R. S., Rinne, J. O., Sui, Y., Cazorla, P., Ricart, J., Meneses, K., Caputo, A., Tariot, P. N., Reiman, E. M., & Graf, A.
- Affiliations
- Novartis (Switzerland) (CH)
- Banner Alzheimer’s Institute (US)
- Georgetown University Medical Center (US)
- University of Turku (FI)
- Clinical Development, Neuroscience Novartis Pharmaceuticals East Hanover New Jersey USA
- Novartis (Spain) (ES)
- Corresponding author
- Riviere, Marie‐Emmanuelle
- ORCID
- Venue
- Alzheimer's & Dementia
- Publisher
- Wiley
- Published
- 2023-12-25
- Volume
- 20
- Issue
- 3
- Pages
- 1839-1850
- ISSN
- 1552-5260 (ISSN-L)
- 1552-5279
- PMC
- PMC10984441
- OpenAlex
- W4390202535
- Cited by
- 28
- References
- 30
- Citations by year
- 2026: 7 · 2025: 14 · 2024: 6 · 2023: 1
- FWCI
- 4.95
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Alzheimer s & Dementia (publishedVersion, cc-by-nc)
- PubMed Central (publishedVersion, cc-by-nc)
- PubMed (publishedVersion)
- UTUPub (University of Turku) (submittedVersion)
- UTUPub (University of Turku) (submittedVersion, cc-by-nc)
- Funders
- National Institute on Aging (1UF1AG046150)
- Alzheimer's Association
- Foundation for Biomedical Research and Innovation
- GHR Foundation
- Topics
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- MeSH terms
- Aged, Alzheimer Disease, Amyloid, Brain, Homozygote, Humans, Immunotherapy, Middle Aged, Amyloid beta-Peptides, Positron-Emission Tomography, Apolipoprotein E4, Plaque, Amyloid
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