Anti-MTBR Tau Antibody Etalanetug Given FDA Fast Track Designation

According to a new announcement from Eisai, the company has received FDA fast track for its investigational drug etalanetug, an anti-tau antibody that targets specific tau species containing microtubule binding region (MTBR) for Alzheimer disease (AD).¹

Etalanetug is currently being evaluated with a standard of care treatment, an anti-amyloid β protofibril antibody, lecanemab (Leqembi; Eisai), in two clinical trials: the Tau NexGen phase 2/3 clinical trial (NCT05269394) for dominantly inherited AD (DIAD), led by the Dominantly Inherited Alzheimer Network Trials Unit (DIAN-TU) at Washington University School of Medicine in St. Louis, and a Phase II clinical trial (Study 202, NCT06602258) targeting sporadic early AD.

In a previous, phase 1b/2, open-label clinical trial (NCT04971733)of etalanetug in patients with DIAD, treatment with the medication resulted in significant effect on both early and late tau biomarkers in treated patients. Otherwise known asE2814, the agent did not affect phosphorylated tau (p-tau)217 or MTBR-tau243 levels in healthy volunteers, suggesting its effects are specific to those with tau pathology and thus further supporting its clinical development.

Led by Kristin Wildsmith, PhD, a senior director of translational medicine at Eisai, patients on the drug showed a 30.4% reduction in p-tau217 after 12 weeks of treatment (n = 7), and an even greater reduction at 36 weeks (48.6%; n = 5) and 108 weeks (57.9%; n = 2). E2814, a drug designed to bind to the microtubule biding region (MTBR) of tau, resulted in a 50.6% reduction in concentrations of MTBR-tau243 in early-stage patients (n = 7) after 12 weeks of treatment. Notably, the greatest reduction in MTBR-tau243 levels (-71.6%) occurred at week 36 (n=4) and was maintained up to 108 weeks (n=2).²

Read More: Anti-Tau Agent E2814 Shows Impact on Early and Late Tau Biomarkers, Further Supporting Development

The study, which was designed for initial safety, pharmacokinetic, target engagement, and proof-of-mechanism of etalanetug, also analyzed and compared cerebrospinal fluid (CSF) of healthy volunteers from the previously completed phase 1 E2814-G000-001 trial, to compare pharmacodynamic effects on early and late tau biomarkers in a population without tau pathology. In this group of individuals, treatment with etalanetug resulted in no effect on MTBR-tau243 or p-tau217 after 12 weeks of treatment.

AD is a chronic, progressive, neurodegenerative disease characterized by formation of protein deposits known as plaques made of amyloid-beta aggregates and neurofibrillary tangles made of tau protein in the brains of people living with AD. Data shows that amyloid-beta protofibrils and tau tangles play roles in the neurodegeneration process.

REFERENCES
1. Anti-MTBR (microtubule binding region) Tau Antibody Etalanetug Granted FDA Fast Track. News Release. Eisai. September 16, 2025. Accessed October 22, 2025.https://www.prnewswire.com/news-releases/anti-mtbr-microtubule-binding-region-tau-antibody-etalanetug-granted-fda-fast-track-designation-302558422.html
2. Horie K, Charil A, Barthelemy N, et al. Anti-tau therapeutic antibody, E2814, reduces early and late tau pathology biomarkers in patients with DIAD. Presented at: Clinical Trials on Alzheimer’s Disease conference; October 29-November 1, 2024; Madrid, Spain. ABSTRACT OC04