Bristol Myers Squibb announced that the US Food and Drug Administration (FDA) has granted Fast Track Designation to BMS-986446, a potential best-in-class anti–microtubule binding region tau (anti–MTBR-tau) antibody currently in phase 2 development for the treatment of early Alzheimer disease (AD).
BMS-986446 is a humanized monoclonal antibody designed to target multiple domains within the microtubule binding region of tau—a highly pathogenic protein fragment linked to the formation of neurofibrillary tangles and cognitive decline in AD. By binding to specific regions of tau, the antibody aims to block its cell-to-cell transmission and uptake while engaging microglia through Fc receptor activation to enhance tau clearance via phagocytosis. Together, these mechanisms are intended to slow or prevent the spread of pathological tau, potentially modifying the underlying course of Alzheimer disease and delaying its progression.
“The FDA’s Fast Track Designation for BMS-986446 highlights both the urgent need for innovative Alzheimer disease therapies and the promise of our investigational anti–MTBR-tau antibody to alter the trajectory of disease progression,” said Laura Gault, Senior Vice President and Head of Neuroscience Development at Bristol Myers Squibb. “Our approach to Alzheimer disease spans the continuum of care—exploring disease-modifying agents like BMS-986446 alongside symptomatic treatments to address behavioral changes such as psychosis and agitation that deeply affect patients and their caregivers.”
In preclinical studies, BMS-986446 significantly reduced tau uptake and spread, mitigated behavioral deficits, and was found to co-localize with tau pathology in AD brain tissue. Results from a phase 1 trial in healthy participants also demonstrated that the antibody was safe and well tolerated across three dose levels.
The ongoing TargetTau-1 trial is a randomized, double-blind, placebo-controlled, global phase 2 study evaluating the efficacy, safety, and tolerability of multiple doses of BMS-986446 in adults aged 50–80 years with early Alzheimer disease. The primary endpoint is change from baseline in Clinical Dementia Rating Scale–Sum of Boxes (CDR-SB) score at 76 weeks, measuring clinical decline compared with placebo.
Key secondary endpoints include:
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Effects on brain tau deposition measured via PET imaging,
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Cognitive and functional outcomes assessed by validated rating scales, and
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Overall safety and tolerability.
Exploratory objectives will assess pharmacokinetics, immunogenicity, plasma biomarkers, MRI changes, and patient-reported quality of life measures. The phase 2 study is fully enrolled, with estimated completion in November 2027.
