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Meta-Analysis
. 2023 Oct;19(10):4619-4628.
doi: 10.1002/alz.13031. Epub 2023 Mar 22.

Targeting amyloid β in Alzheimer's disease: Meta-analysis of low-dose solanezumab in Alzheimer's disease with mild dementia studies

Karen C Holdridge  1 , Roy Yaari  1 , Deirdre B Hoban  1 , Scott Andersen  1 , John R Sims  1
Affiliations
Meta-Analysis

Targeting amyloid β in Alzheimer's disease: Meta-analysis of low-dose solanezumab in Alzheimer's disease with mild dementia studies

Karen C Holdridge et al. Alzheimers Dement. 2023 Oct.

Abstract

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.

Trial registration: ClinicalTrials.gov NCT00905372 NCT00904683 NCT01900665.

Keywords: Alzheimer's disease; anti-amyloid monoclonal antibody; clinical trial; meta-analysis; solanezumab.

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References

REFERENCES

    1. Hyman BT, Phelps CH, Beach TG, et al. National Institute on Aging-Alzheimer's Association guidelines for the neuropathologic assessment of Alzheimer's disease. Alzheimers Dement. 2012;8(1):1-13.
    1. Selkoe DJ. The molecular pathology of Alzheimer's disease. Neuron. 1991;6(4):487-498.
    1. Hardy J. New insights into the genetics of Alzheimer's disease. Ann Med. 1996;28(3):255-258.
    1. Naslund J, Haroutunian V, Mohs R, et al. Correlation between elevated levels of amyloid beta-peptide in the brain and cognitive decline. JAMA. 2000;283(12):1571-1577.
    1. Price DL, Sisodia SS, Borchelt DR. Genetic neurodegenerative diseases: the human illness and transgenic models. Science. 1998;282(5391):1079-1083.

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