FDA Grants Fast Track Designation to BMS-986446 for Treatment of Early Alzheimer Disease

BMS-986446, an anti-microtubule binding region-tau (anti-MTBR-tau) therapy, received a fast track designation for treatment of patients with early Alzheimer disease (AD). The decision is supported by data from the phase 2 TargetTau-1 trial (NCT06268886).¹

“The FDA’s fast track designation for BMS-986446 underscores the urgent need for innovative therapies for [AD] and recognizes the potential of this investigational [anti-MTBR-tau] antibody to meaningfully alter the trajectory of disease progression,” Laura Gault, senior vice president and head of development, Neuroscience, Bristol Myers Squibb, said in a press release. “Bristol Myers Squibb is taking a continuum of care approach to Alzheimer’s disease, studying investigational medicines such as those targeting tau to change the course of the disease as well as several symptomatic treatment options that can address severe shifts in behavioral symptoms, such as psychosis and agitation, that significantly impact patients and their caregivers.”²

AD is a progressive neurodegenerative disease characterized by changes in the brain that cause neurons to die over time, leading to impaired memory, language, and cognitive functioning. It is the most common type of dementia in adults, with rates expected to grow to 82 million by 2050. These statistics underscore the crucial need for prevention and efficacious, early therapies for patients in earlier stages of disease.³

A novel discovery of the underlying pathology of AD is the identification of the tau protein. In AD, pathological tau protein fragments accumulate and spread through the brain. These fragments contain the microtubule binding region (MTBR), which is associated with neurofibrillary tangle formation and cognitive.²

BMS-986446 is an investigational, humanized monoclonal antibody binds to specific regions of the tau protein, namely R1-R3 in the MTBR, to prevent the cell-to-cell spread and uptake of tau. Additionally, the agent activates immune cells in the brain to promote clearance of tau through phagocytosis. In preclinical models, the agent significantly reduced tau uptake and spread.²

The efficacy of BMS-986446 is supported by data from the randomized, double-blind, placebo-controlled, global proof-of-concept TargetTau-1 trial. Researchers in the study set out to evaluate the efficacy, safety, and tolerability of BMS-986446 for patients with early AD. The study involves about 300 patients (ages 50-80 years) with mild cognitive impairment (MCI) due to AD or mild AD dementia consistent with the National Institute on Aging and the Alzheimer's Association core clinical criteria.^1,2

The trial consists of 3 arms: a placebo group and 2 BMS-986446 assessing 2 dosages. The primary end point is Change from baseline in brain tau deposition as measured by tau positron emission tomography (PET) at week 76. Key secondary outcomes include changes from baseline across multiple clinical outcome measures not limited to the Clinical Dementia Rating Scale Sum of Boxes score, Alzheimer's Disease Rating Scale score, and Alzheimer's Disease Assessment Scale-Cognitive subscale score.^1,2

The researchers reported that BMS-986446 was safe and well tolerated across 3 dose cohorts in a phase 1 study of healthy participants. An ongoing phase 2 study will further assess several biomarkers of tau and amyloid-beta biology to evaluate the impact of BMS-986446 on disease progression.²

REFERENCES

1. Study to evaluate the efficacy, safety, and tolerability of an anti-MTBR Tau monoclonal antibody (BMS-986446) in participants with early Alzheimer's disease (TargetTau-1). Updated July 24, 2025. Accessed October 7, 2025. https://clinicaltrials.gov/study/NCT06268886

2. Bristol Myers Squibb’s anti-MTBR-Tau-targeting antibody, BMS-986446, granted fast track designation by U.S. FDA for the treatment of Alzheimer’s disease. Bristol Myers Squibb. October 1, 2025. Accessed October 7, 2025. https://news.bms.com/news/corporate-financial/2025/Bristol-Myers-Squibbs-Anti-MTBR-Tau-Targeting-Antibody-BMS-986446-Granted-Fast-Track-Designation-by-U-S--FDA-for-the-Treatment-of-Alzheimers-Disease/default.aspx?cid=s_3362819&linkId=865159777

3. Gerlach A. Alzheimer Disease prevalence reaches record high, surpassing 7.2 million cases. Pharmacy Times. May 2, 2025. Accessed October 7, 2025. https://www.pharmacytimes.com/view/alzheimer-disease-prevalence-reaches-record-high-surpassing-7-2-million-cases