Eisai Co. Ltd. presented new data at the 17th annual Clinical Trials on Alzheimer’s Disease (CTAD) conference in Madrid, Spain, highlighting the potential of its anti-MTBR (microtubule binding region) tau antibody, E2814, to inhibit tau propagation in Alzheimer's disease (AD). The company also announced the initiation of a Phase II study (Study 202) of E2814 for sporadic early AD.
Impact on Tau Pathology Biomarkers in DIAD
E2814 is an investigational antibody targeting the MTBR of tau, a region implicated in the formation of neurofibrillary tangles (NFTs), a hallmark of AD. The antibody is designed to prevent the spread of tau seeds, which are believed to propagate tau pathology throughout the brain. A Phase I/II clinical study (Study 103, NCT04971733) evaluated the safety, tolerability, and target engagement of E2814 in patients with Dominantly Inherited Alzheimer’s Disease (DIAD). The study, initiated in June 2021, involved 7 participants who received E2814 for 12 to 24 months. Data from the Dominantly Inherited Alzheimer Network Observational Study (DIAN-obs) served as a reference for biomarker changes.
Compared to the DIAN-obs reference data, patients treated with E2814 exhibited approximately 75% and 50% reductions in cerebrospinal fluid (CSF) MTBR-tau243 and p-tau217 levels, respectively. Furthermore, brain tau accumulation, as measured by tau PET imaging, was stabilized or showed a trend toward decrease in DIAD subjects administered E2814. These findings suggest that E2814 may inhibit tau propagation and reduce tau aggregate accumulation in the brains of individuals with DIAD. These results will be further investigated in the ongoing Phase II/III Tau NexGen study (NCT05269394) with DIAD patients and the Phase II 202 study (NCT06602258) with sporadic early Alzheimer’s disease (AD) patients.
Phase II Study Initiation
Eisai initiated a Phase II clinical study (Study 202) in September 2024 in the United States, with plans to expand to Japan. This placebo-controlled, double-blind, parallel-group, dose-exploration study will assess the safety, tolerability, and biomarker efficacy of E2814 in individuals with early AD who are also receiving lecanemab as a backbone anti-Aβ therapy.
Eisai is focusing on neurology as a key therapeutic area and aims to develop innovative medicines for diseases with high unmet needs, such as Alzheimer's disease.
