Exploratory analyses of clinical outcomes from the BIIB080 phase 1b study in mild Alzheimer’s disease

This study conducted exploratory analyses of the effects of BIIB080, a MAPT (microtubule-associated protein tau)-targeting antisense oligonucleotide, in participants with mild Alzheimer’s disease. A multicenter, randomized, double-blind, phase 1b trial was conducted as a placebo-controlled, multiple-ascending dose (MAD) study followed by an open-label, long-term extension (LTE). During the MAD study, participants were randomized and received either intrathecal placebo or BIIB080 10 mg (n = 6), 30 mg (n = 6) or 60 mg (n = 9) every 4 weeks or 115 mg (n = 13) every 12 weeks (Q12W). During the LTE, participants received high-dose BIIB080 (60 mg (n = 7) or 115 mg (n = 9) Q12W). BIIB080 was generally well tolerated. Here we present findings from exploratory analyses, which showed a consistent trend of slowed decline on cognitive, functional and global measures favoring BIIB080 high-dose groups at the end of both study periods. This favorable trend is supported by reported reductions from baseline in brain neurofibrillary tangles measured with tau positron emission tomography. Trial registration: ClinicalTrials.gov identifier: NCT03186989 . This exploratory analysis of a phase 1b study evaluating BIIB080, a MAPT-targeting antisense oligonucleotide, in mild Alzheimer’s disease indicates favorable trends of high-dose BIIB080 in slowing cognitive and functional decline, supporting the need for future trials evaluating clinical efficacy of BIIB080 in mild Alzheimer’s disease.