Eisai Co., Ltd. announced that etalanetug (development code: E2814), an investigational anti-MTBR (microtubule binding region) tau antibody, has received Fast Track designation from the U.S. Food and Drug Administration. The designation is designed to facilitate and expedite development of new drugs addressing unmet medical needs in serious or life-threatening conditions such as Alzheimer's disease.
Targeting Tau Pathology in Alzheimer's Disease
Alzheimer's disease is characterized by the formation of protein deposits including amyloid-beta plaques and neurofibrillary tangles made of tau protein in the brain. Data demonstrate that amyloid-beta protofibrils and tau tangles play roles in the neurodegeneration process. Etalanetug specifically targets tau species containing MTBR, which are tau seeds that spread tau pathology to different brain regions.
The antibody was discovered through a research collaboration between Eisai and University College London, representing a novel approach to addressing tau-related neurodegeneration.
Clinical Trial Evidence
In the Phase I/II clinical trial (Study 103, NCT04971733) targeting patients with Dominantly Inherited Alzheimer's Disease (DIAD), etalanetug demonstrated target engagement with MTBR-tau species in cerebrospinal fluid. The study showed a reduction in CSF MTBR-tau243, a biomarker reflecting brain tau pathophysiology, as well as a trend towards suppression or decrease in tau PET signal.
These results suggest that etalanetug inhibited tau propagation and suppressed the accumulation of tau aggregates in brains of people living with DIAD. CSF MTBR-tau243 and tau phosphorylated at residue 217 (p-tau217) have been reported as fluid biomarkers related to Alzheimer's disease tau pathology, with these biomarkers included in the Revised criteria for diagnosis and staging of Alzheimer's disease published by the National Institute on Aging and the Alzheimer's Association in June 2024.
Ongoing Clinical Development
Etalanetug is currently being evaluated in combination with lecanemab, an anti-amyloid β protofibril antibody, in two clinical trials. The Tau NexGen Phase II/III clinical trial (NCT05269394) for DIAD is led by the Dominantly Inherited Alzheimer Network Trials Unit (DIAN-TU) at Washington University School of Medicine in St. Louis. Additionally, a Phase II clinical trial (Study 202, NCT06602258) is targeting sporadic early Alzheimer's disease.
Regulatory Pathway and Implications
Fast Track designation provides opportunities for frequent interactions with the FDA and, if supported by clinical data at the time of New Drug Application submission, the drug may be eligible for Accelerated Approval and Priority Review. The designation is available for drugs that demonstrate potential advantage over existing treatments or address conditions where no treatments exist.
Following the development of treatments targeting amyloid beta, the availability of treatments targeting tau is expected to represent a major breakthrough in Alzheimer's disease treatment. Eisai positions neurology as one of its key therapeutic areas and continues to focus on creating innovation in novel medicine development based on cutting-edge neurology research to contribute to improving outcomes for individuals and families affected by diseases with high unmet needs, including dementia.
