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Donanemab Improves Exploratory Plasma Biomarkers in Early Alzheimer Disease
Donanemab treatment significantly lowered plasma biomarkers phosphorylated tau217 (pTau217) and glial fibrillary acidic protein compared with placebo in patients with early symptomatic Alzheimer disease, according to an exploratory post hoc analysis of data from the TRAILBLAZER-ALZ study. Researchers published their findings online ahead of print in JAMA Neurology.
“These results are consistent with, and extend, findings of changes in cerebrospinal fluid and plasma biomarkers with other anti-amyloid-β antibodies,” researchers wrote. “They add weight to the hypothesis that reduction of amyloid by anti-amyloid-β antibodies could have downstream effects consistent with disease modification and suggest that fluid biomarkers could have a role in monitoring response to treatments (at least as a group measure of target engagement/amyloid clearance) in future clinical trials.”
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Researchers from TRAILBLAZER-ALZ, a phase 2 randomized clinical trial, previously reported robust amyloid plaque reduction with donanemab in patients with early symptomatic Alzheimer disease. Donanemab also slowed disease progression by a third as measured by the Integrated Alzheimer’s Disease Rating Scale. This post hoc analysis assessed the drug’s effect on plasma levels of biomarkers pTau217, glial fibrillary acidic protein, neurofilament light chain, and amyloid-β 42/40 in study participants.
According to findings, plasma levels of pTau217 and glial fibrillary acidic protein were significantly lower as early as 12 weeks after the start of treatment with donanemab compared with placebo. However, no significant differences in plasma amyloid-β 42/40 and neurofilament light chain were observed between treatment arms at the end of the study.
Changes in plasma pTau217 and glial fibrillary acidic protein positively correlated with the change in brain amyloid plaques as measured by amyloid positron emission tomography imaging, the study found.
“These easily accessible plasma biomarkers might provide additional evidence of Alzheimer disease pathology change through anti-amyloid therapy,” the authors wrote. “Usefulness in assessing treatment response will require further evaluation.”
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