Anti-Tau Antibody Etalanetug Shows Reductions in Novel Biomarker of Tau Tangle Pathology in Dominantly Inherited Alzheimer Disease

Treatment with the investigational anti-tau antibody etalanetug (E2814; Eisai, Tokyo, Japan) for individuals with dominantly inherited Alzheimer disease (DIAD) was associated with reductions in eMTBR-tau243, a novel cerebrospinal fluid (CSF) biomarker that reflects tau tangle pathology and consists of tau fragments that contain amino acid 243 and part of the microtubule binding region (MTBR), produced through endogenous cleavage of the C-terminal side of residue 256. The findings from the phase 1b/2 E2814-G000 clinical study (NCT04971733), presented at the 18th annual Clinical Trials on Alzheimer’s Disease (CTAD) conference, suggest robust target engagement and provide further proof-of-mechanism for this investigational agent. Etalanetug, which is designed to prevent the seeding and propagation of tau pathology by binding to the MTBR of tau protein, received Food and Drug Administration (FDA) Fast Track Designation in Q3 of this year, according to an announcement from Eisai.

In the open-label E2814-G000-103 study, 7 participants with mild to moderate cognitive impairment due to DIAD received intravenous etalanetug treatment every 4 weeks at escalating doses (750 mg, 1500 mg, 3000 mg, and 4500 mg), followed by maintenance dosing at 4500 mg for up to 108 weeks. Plasma and cerebrospinal fluid (CSF) samples were collected every 3 months. Levels of MTBR-tau243 (243-254 tryptic residue) and eMTBR-tau243 (243-256 endogenous form) were quantified using immunoprecipitation followed by mass spectrometry. Drug-interference testing confirmed that assay performance was unaffected by etalanetug in plasma or CSF.

The study reported the following findings:

• In CSF, etalanetug treatment was associated with reductions in eMTBR-tau243 by 62% at 3 months and 89% at 9 months.
• Etalanetug treatment was associated with reductions of plasma eMTBR-tau243 by 78% at 3 months and >90% at 9 months.
• In plasma, eMTBR-tau243 decreased by 25% after 2 doses and by 78% after 3 doses of etalanetug 750 mg, with maximal reductions >90% were observed and maintained for the duration of treatment.
• Researchers found that the non-deamidated and deamidated forms of CSF eMTBR-tau243 were highly correlated (r=0.99 Pearson; r=0.97 Spearman).
• Plasma eMTBR-tau243 was undetectable in healthy control participants given placebo or etalanetug.

Source: Eisai U.S. Eisai presents new data on anti-tau antibody etalanetug (E2814) at CTAD 2025. Eisai U.S. News & Press Releases. Published December 1, 2025. Accessed December 2, 2025. https://media-us.eisai.com/2025-12-01-Eisai-Presents-New-Data-on-Anti-Tau-Antibody-Etalanetug-E2814-at-CTAD-2025

Wildsmith K, Horie K, Boyd P, et al. Anti-tau therapeutic antibody, etalanetug, reduces the novel biomarker plasma eMTBR-tau243 in patients with DIAD. Presented at: 18th annual Clinical Trials on Alzheimer’s Disease Conference; December 1-4, 2025; San Diego, California.