Etalanetug shows over 90% tau biomarker reduction in Eisai’s DIAD trial update at CTAD 2025

Eisai Co., Ltd. has unveiled new clinical data for its investigational anti-tau antibody etalanetug (E2814), highlighting significant reductions in a novel tau pathology biomarker in patients with dominantly inherited Alzheimer’s disease (DIAD). The data were presented at the 18th Clinical Trials on Alzheimer’s Disease (CTAD) conference, underscoring Eisai’s continued momentum in developing multi-target disease-modifying therapies for Alzheimer’s.

The new analysis from the Phase Ib/II study E2814-103 showed that etalanetug led to a reduction of over 90 percent in plasma levels of eMTBR-tau243 after nine months of treatment. This biomarker, found in both cerebrospinal fluid (CSF) and plasma, is closely correlated with tau PET signal and reflects the pathological seeding and spread of tau tangles in the brain—a key driver of neurodegeneration in Alzheimer’s disease.

Etalanetug is designed to bind to the microtubule-binding region (MTBR) of the tau protein and block its ability to propagate between neurons. In the study, which enrolled seven individuals with DIAD, imaging and biomarker data suggest the antibody may suppress or stabilize pathological tau accumulation, particularly in early stages of the disease.

How does eMTBR-tau243 improve measurement of tau pathology in Alzheimer’s disease?

Eisai’s presentation highlighted eMTBR-tau243 as a critical biomarker that could redefine how tau pathology is monitored in Alzheimer’s disease trials. The biomarker includes fragments of tau protein spanning amino acid residue 243 and the MTBR domain, with cleavage at residue 256. It arises during neurofibrillary tangle formation, making it directly relevant to the key pathological hallmark of Alzheimer’s disease.

Unlike older biomarkers that often measure broader neurodegeneration markers, eMTBR-tau243 provides a specific signal for the tau tangle cascade. Tau PET imaging has long been considered the gold standard for detecting and tracking tau burden, but it remains expensive and logistically intensive. Eisai’s development of this plasma biomarker opens the possibility of using simple blood tests to assess tau pathology changes, creating a new paradigm for non-invasive disease tracking in clinical and real-world settings.

The correlation between eMTBR-tau243 and tau PET signal has been validated in both cerebrospinal fluid and plasma, further increasing its potential utility. According to Eisai’s internal findings, reductions in eMTBR-tau243 tracked with stabilization or decreases in tau PET signal in patients receiving etalanetug.

What did the Phase Ib/II trial reveal about etalanetug’s biomarker effects?

The Phase Ib/II study enrolled a small cohort of seven individuals with genetically confirmed dominantly inherited Alzheimer’s disease, a rare but aggressive form of early-onset dementia. In three of those participants, tau accumulation was measured using positron emission tomography (PET) imaging. Eisai reported that the tau PET signal was either stabilized or trending toward reduction over the course of etalanetug treatment, suggesting that the drug may be slowing the progression of tau aggregation in the brain.

Beyond imaging, the study measured concentrations of eMTBR-tau243 in cerebrospinal fluid and plasma at multiple intervals. The results showed that cerebrospinal fluid levels of the biomarker decreased by 62 percent at three months and by 89 percent at nine months. In plasma, reductions were even more pronounced, with levels dropping by 78 percent at three months and exceeding 90 percent at the nine-month mark. These reductions support the proposed mechanism of action of etalanetug in targeting and inhibiting tau seeding and spreading.

Where does etalanetug fit into Eisai’s dual-pathway Alzheimer’s strategy?

Etalanetug is currently being evaluated in two global clinical studies as part of a broader dual-pathway approach to Alzheimer’s disease, combining anti-amyloid and anti-tau therapies. In the Tau NexGen Phase II/III trial, the antibody is being tested in combination with lecanemab, Eisai’s FDA-approved anti-amyloid protofibril antibody commercialized as LEQEMBI. That study is being conducted by the Dominantly Inherited Alzheimer Network Trials Unit (DIAN-TU) and coordinated by Washington University School of Medicine in St. Louis.

The second trial, known as Study 202, is a Phase II global randomized study evaluating etalanetug in individuals with early-stage sporadic Alzheimer’s disease. Similar to Tau NexGen, this study also examines the therapeutic effect of etalanetug in combination with lecanemab. These ongoing trials aim to determine whether combining tau-targeting and amyloid-targeting agents can offer additive or synergistic benefits in halting or reversing cognitive decline.

Etalanetug was granted Fast Track designation by the U.S. Food and Drug Administration in September 2025, signaling regulatory recognition of its potential to address a serious unmet need in Alzheimer’s disease. The designation may enable expedited review timelines and more frequent engagement with regulators as development progresses.

Why are researchers watching tau suppression strategies more closely in 2025?

While the Alzheimer’s field has historically been dominated by amyloid-targeting strategies, there has been growing consensus that tau propagation plays an equally important role in disease progression. Amyloid plaques tend to accumulate early in the disease course, but tau tangles more closely correlate with cognitive decline. Several recent failures of amyloid-targeting monotherapies have further amplified interest in tau-targeted and combination approaches.

The results from Eisai’s etalanetug trial add to a growing body of data supporting the feasibility of tau-targeting monoclonal antibodies. With measurable effects on a novel fluid biomarker, the drug could potentially complement amyloid-targeting therapies by addressing the downstream consequences of neuronal toxicity and neurodegeneration.

Analysts following the Alzheimer’s pipeline believe that combination regimens may become the future standard of care, particularly in genetically driven or early-stage populations. If ongoing studies confirm the safety and efficacy of etalanetug in larger cohorts, it could position Eisai as a global leader in dual-pathway Alzheimer’s care.

What are the implications for Alzheimer’s diagnostics and patient monitoring?

One of the most notable aspects of Eisai’s update is the potential to use plasma eMTBR-tau243 as a simple, scalable, and cost-effective biomarker to monitor disease progression or therapeutic response. This could have significant implications for both clinical trials and real-world care, making it easier to track how patients respond to treatments over time without relying solely on imaging or lumbar punctures.

Blood-based biomarkers are increasingly viewed as critical to early diagnosis, especially in resource-limited settings or among patients who cannot undergo imaging due to cost or comorbidities. The strong correlation between tau PET signal and eMTBR-tau243 levels reinforces its validity and utility as a monitoring tool.

As more tau-targeted therapies enter the pipeline, having a sensitive and specific biomarker that reflects disease activity will be essential for comparing efficacy, tailoring treatment plans, and potentially accelerating regulatory approvals.

What happens next in the etalanetug development timeline?

Eisai is expected to provide further updates from the Tau NexGen and Study 202 trials over the next year. These results will be crucial in validating the clinical relevance of the biomarker reductions seen in the Phase Ib/II study. Depending on the strength of the data, etalanetug could be advanced toward late-stage development or regulatory submission in the coming years.

Institutional interest in dual-pathway neurodegenerative therapies is rising, and the Fast Track designation may support quicker commercialization pathways if efficacy is confirmed. Investors and industry stakeholders will be watching closely for interim readouts and additional biomarker data from both ongoing studies.

Eisai’s strategic investment in tau and its integration with lecanemab demonstrates the company’s long-term commitment to redefining Alzheimer’s treatment. Whether etalanetug becomes a standalone therapeutic or part of a fixed-dose combination, its development marks a pivotal step in addressing tau pathology head-on.

What are the key takeaways from Eisai’s CTAD 2025 etalanetug data release?

• Eisai presented new data on its anti-tau antibody etalanetug (E2814) at the CTAD 2025 conference.

• The Phase Ib/II study in DIAD patients showed up to 90% reduction in plasma eMTBR-tau243 at nine months.

• eMTBR-tau243 is a novel fluid biomarker reflecting active tau tangle formation, measurable in blood.

• Etalanetug is being evaluated in combination with LEQEMBI in two ongoing Phase II/III trials.

• The antibody received Fast Track designation from the U.S. Food and Drug Administration in September 2025.

• The drug is part of Eisai’s broader dual-pathway strategy targeting both amyloid and tau pathology in Alzheimer’s disease.