Highlighting Research Progress in Tau-Targeting Therapy for Alzheimer Disease: Diana Gallagher, MD

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"Targeting tau is something that we've known for a long time—the aggregation of this abnormal protein is coincident with the clinical decline for patients. But getting a drug at that target has been pretty tricky because it resides predominantly intracellularly."

Although the introduction of amyloid-targeting disease-modifying therapies may represent a significant step forward in Alzheimer disease (AD) treatment, considerable gaps in care still exist. Aβ accumulation is thought to occur early in AD development, yet clinicopathological evidence shows that the extent and spread of tau neurofibrillary tangles more strongly correlate with the degree of clinical decline. Currently, BIIB080 (Biogen), an investigational antisense oligonucleotide that inhibits translation of tau mRNAs into protein, is in development for the treatment of AD. Prior results reported from a phase 1b study (NCT03186989) of BIIB080 revealed a marked effect of the agent on cerebrospinal fluid (CSF) tau and tau PET biomarkers.

At the recently concluded 2025 Alzheimer’s Association International Conference, held July 27-30, in Toronto, Canada, researchers presented baseline characteristics from the phase 2 CELIA study (NCT05399888) which will assess the therapeutic potential of BIIB080 compared with placebo in older adults with early AD. In the study, investigators randomized 416 participants aged 50-80 years, with MCI or mild AD dementia, to receive 1 of 3 dose regimens of intrathecal BIIB080 or placebo every 12 or 24 weeks during the 76-week placebo-controlled period. The primary end point of the trial is the dose-response in change from baseline to week-76 on the Clinical Dementia Rating Scale Sum of Boxes.

Coauthor of the presented analysis Diana Gallagher, MD, head of AD, MS and Immunology Development Units at Biogen, spoke with NeurologyLive^® at AAIC 2025, highlighting the company’s ongoing focus on tau as a therapeutic target in AD following years of work on amyloid. During the conversation, she talked about the early data of BIIB080 showing biological engagement and trends toward clinical improvement. Gallagher noted that the CELIA study is now fully enrolled and will evaluate intrathecal administration of BIIB080 with dosing either 2 or 4 times per year. Diana also discussed the broader implications of fluid and imaging biomarkers as well as the importance of leveraging past experience in amyloid research to accelerate progress in tau therapy.

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REFERENCES
1. Shulman M, Wu S, Xie J, et al. Baseline characteristics from CELIA: A Phase 2 study to evaluate BIIB080 in participants with Early Alzheimer’s Disease. Presented at: 2025 Alzheimer’s Association International Conference; July 27-31; Toronto, Canada. Abstract 103364.