Targeting amyloid β in Alzheimer’s disease: Meta-analysis of low-dose solanezumab in Alzheimer’s disease with mild dementia studies
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INTRODUCTION: Solanezumab is a monoclonal antibody that binds to the mid-domain of soluble amyloid β peptide. This meta-analysis evaluated the effect of low-dose solanezumab on clinical progression in three phase 3 studies. METHODS: The population comprised patients aged ≥55 years with Alzheimer's disease (AD) with mild dementia, randomized to 400 mg solanezumab or placebo every 4 weeks for 80 weeks. Frequentist mixed-model repeated-measures (MMRM) and Bayesian disease progression model (DPM) longitudinal analyses were conducted. RESULTS: Pooled MMRM analyses showed a statistically significant effect of solanezumab across cognitive and functional outcome measures. DPM results were generally consistent with MMRM results, ranging from 15% to 30% slowing of clinical progression. DISCUSSION: These analyses suggest low-dose solanezumab slows clinical progression of AD with mild dementia. The ongoing A4 solanezumab study in participants with preclinical AD will ascertain the effect of a higher dose of solanezumab in an earlier disease stage. HIGHLIGHTS: Individual EXPEDITION studies were negative but suggest low-dose solanezumab had an effect in slowing the clinical progression of Alzheimer's disease (AD) with mild dementia. At 80 weeks, mixed-model repeated-measures analyses showed numeric reductions in measures of clinical decline in solanezumab-treated arms compared with placebo across almost every outcome measure, and statistical significance in multiple outcome measures in each study. Pooled analyses suggest a high probability that low-dose solanezumab has at least some effect on slowing the clinical progression of AD with mild dementia. Across cognitive and functional outcome measures, estimates from disease progression model analyses range from 15% to 30% slowing of decline with low-dose solanezumab in AD with mild dementia.
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AN-1792 was withdrawn during Phase II of the trial due to side effects associated with meningoencephalitis, reported in 6% of patients.
“However, AN-1792 was withdrawn during Phase II of the trial due to side effects associated with meningoencephalitis, which were reported in 6% of patients [140,141,142,143,144].”
From Recent Advances in Therapeutics for the Treatment of Alzheimer’s Disease (2024) · cites this paper as [144]
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- Authors
- Holdridge, K. C., Yaari, R., Hoban, D. B., Andersen, S., & Sims, J. R.
- Affiliations
- Eli Lilly (United States) (US)
- Corresponding author
- Holdridge, Karen C.
- Venue
- Alzheimer's & Dementia
- Publisher
- Wiley
- Published
- 2023-03-22
- Volume
- 19
- Issue
- 10
- Pages
- 4619-4628
- ISSN
- 1552-5260 (ISSN-L)
- 1552-5279
- OpenAlex
- W4353015180
- Cited by
- 19
- References
- 24
- Citations by year
- 2026: 3 · 2025: 4 · 2024: 5 · 2023: 7
- FWCI
- 3.37
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Alzheimer s & Dementia (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- Funders
- Eli Lilly and Company
- Topics
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Health Sciences › Medicine › Pharmacology › Cholinesterase and Neurodegenerative Diseases
- Keywords
- solanezumab, Alzheimer's disease
- MeSH terms
- Alzheimer Disease, Bayes Theorem, Humans, Randomized Controlled Trials as Topic, Amyloid beta-Peptides, Disease Progression, Antibodies, Monoclonal, Humanized
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