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BIIB080 Reduces Tau Biomarkers in Patients With Mild Alzheimer Disease
BIIB080 reduced biomarkers associated with tau pathophysiology in patients with mild Alzheimer disease, according to results from a phase 1b trial published in JAMA Neurology.
“Accumulation of hyperphosphorylated, tangled microtubule-associated protein tau (MAPT) is a pathological hallmark of Alzheimer disease associated with disease progression and cognitive decline,” wrote first author Amanda L. Edwards, PhD, of Biogen, Cambridge, Massachusetts, and coauthors.
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The double-blind clinical trial investigated the effect of BIIB080, an antisense oligonucleotide that targets MAPT pre–messenger RNA, on tau biomarkers in 46 patients with mild Alzheimer disease and confirmed amyloid pathology. For a 36-week multiple-ascending dose phase, participants were randomized 3:1 to BIIB080 or placebo and received intrathecal administration of either 10 mg every 4 weeks, 30 mg every 4 weeks, 60 mg every 4 weeks, or 115 mg every 12 weeks. During an open-label extension that lasted up to 71 weeks, participants received BIIB080 at doses of 60 mg every 12 weeks or 115 mg every 12 weeks.
In the multiple-ascending dose period, BIIB080 was associated with a dose-dependent reduction in cerebrospinal fluid (CSF) total tau (the 2 higher-dose cohorts showed 56% and 51% reductions) and phosphorylated tau 181. Reductions were maintained or continued in the long-term extension, according to the study. In addition, brain neurofibrillary tangles measured with tau positron emission tomography were reduced from baseline across all regions assessed at week 100 with BIIB080 compared with placebo.
BIIB080 was generally well tolerated, the study found.
“In this randomized clinical trial, BIIB080 reduced tau biomarkers, including CSF total tau, CSF phosphorylated tau 181, and tau positron emission tomography, which is associated with cognitive decline, in participants with mild Alzheimer disease,” researchers wrote. “Effects of BIIB080 on biomarkers and clinical outcomes are being further evaluated in a phase 2 trial.”
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