Eisai has announced promising clinical findings regarding its anti-MTBR (microtubule binding region) tau antibody, E2814, at the 17th annual Clinical Trials on Alzheimer’s Disease (CTAD) conference. The data suggest that E2814 inhibits tau propagation and suppresses the accumulation of tau aggregates in the brains of individuals with Dominantly Inherited Alzheimer’s Disease (DIAD). Furthermore, Eisai has initiated a Phase II clinical study (Study 202) to investigate E2814 in sporadic early Alzheimer’s Disease (AD).
Impact on Tau Pathology Biomarkers in DIAD
E2814 is an investigational antibody designed to target the MTBR of tau, a region crucial for tau aggregation and propagation in Alzheimer's disease. Neurofibrillary tangles (NFTs), a pathological hallmark of AD, are believed to spread through synaptically connected pathways in the brain. The study (Study 103, NCT04971733) aimed to evaluate the safety, tolerability, and target engagement of E2814 in DIAD patients. Seven participants were administered E2814 for 12 to 24 months. Data from the Dominantly Inherited Alzheimer Network Observational Study (DIAN-obs) were used as references to evaluate biomarker changes in E2814 treatment.
Compared to the DIAN-obs reference data, patients treated with E2814 showed approximately 75% and 50% reductions in cerebrospinal fluid (CSF) MTBR-tau243 and p-tau217 levels, respectively. These reductions reflect a significant impact on tau pathophysiology. Additionally, brain tau accumulation, as measured by tau PET, was stabilized or showed a trend toward decrease in DIAD subjects who received E2814. These findings suggest that E2814 effectively inhibits tau propagation and reduces the accumulation of tau aggregates in the brains of individuals with DIAD. The ongoing Phase II/III Tau NexGen study (NCT05269394) and the Phase II 202 study (NCT06602258) will further investigate these effects.
Phase II Clinical 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 study is a placebo-controlled, double-blind, parallel-group, dose exploration study designed to evaluate the safety, tolerability, and biomarker efficacy of E2814 in individuals with early AD who are also receiving lecanemab as a backbone anti-Aβ therapy. This combination approach aims to address both amyloid and tau pathologies in Alzheimer's disease.
Eisai is committed to neurology as a key therapeutic area and continues to innovate in the development of novel medicines for diseases with high unmet needs, such as Alzheimer’s disease. E2814 was discovered as part of the research collaboration between Eisai and University College London. E2814 is designed to prevent the spreading of tau seeds within the brains of affected individuals. In addition, E2814 has been selected as an anti-tau therapy in a Phase II/III Tau NexGen study for the treatment of DIAD, conducted by DIAN-TU led by Washington University School of Medicine in St. Louis, is underway.
