Eli Lilly Advances P-tau217 Blood Biomarker Assay for Early and Accurate Alzheimer’s Disease Diagnosis

Compiled by Fan Dongdong

Recently, researchers at Eli Lilly stated at the Clinical Trials on Alzheimer’s Disease (CTAD) conference held in early November that the company’s investigational phosphorylated tau (P-tau) biomarker assay holds promise for earlier and more accurate detection. To this end, Eli Lilly and its wholly owned subsidiary, Avid Radiopharmaceuticals, which is dedicated to the discovery and development of radiopharmaceuticals and imaging methods, are conducting research on P-tau217 as a biomarker of Alzheimer’s disease pathology.

Dr. Jeff Dage, Senior Research Advisor at Eli Lilly, stated, “Recent literature indicates that P-tau levels in patients with Alzheimer’s disease are elevated several years before symptom onset and are consistent with findings on amyloid pathology.” Dr. Dage added, “We aimed to develop a tau antibody capable of binding to specific tau isoforms; therefore, we developed this highly specific assay.” The key components of the assay include a capture antibody (biotin-labeled anti-phospho-thr217-tau antibody), a detection antibody (ruthenium-labeled isoform-specific anti-tau antibody), and calibrators (two antigen-specific synthetic peptides conjugated with PEG linkers). Dr. Dage noted that this assay can be used for the early identification of patients with Alzheimer’s disease and for predicting the risk of disease progression, and it is currently being employed in clinical studies, including new drug trials.

In July this year, Eli Lilly announced the results of a large international trial on P-tau 217 for diagnosing Alzheimer's disease. The results showed that P-tau 217 (tau protein phosphorylated at threonine 217) performed significantly better than other blood-based biomarkers or magnetic resonance imaging (MRI) in distinguishing Alzheimer's disease from other neurodegenerative diseases.

The trial results also demonstrated that P-tau217 shows promise for the diagnosis of Alzheimer’s disease and for early diagnosis in individuals with known genetic risk factors. The study enrolled a total of 1,402 participants across three cohorts. The findings indicated that plasma P-tau217 testing can differentiate Alzheimer’s disease from other neurodegenerative disorders, with significantly higher accuracy than other biomarkers based on plasma or MRI. Moreover, its diagnostic performance showed no significant difference compared to cerebrospinal fluid (CSF) or positron emission tomography (PET)–based assessments.

In addition, Avid Radiopharmaceuticals, a wholly owned subsidiary of Eli Lilly and Company, has developed Tauvid and Amyvid (florbetapir F 18 injection) for the diagnosis of Alzheimer’s disease. Currently, the neuropathological diagnosis of Alzheimer’s disease requires demonstration of the concurrent presence of beta-amyloid neuritic plaques and tau neurofibrillary tangles (tau-NFTs) in the brain. Tauvid is the first and only approved diagnostic agent capable of imaging tau-NFTs in the brain. Meanwhile, Amyvid has also received FDA approval to detect the presence or absence of beta-amyloid plaques in patients with Alzheimer’s disease. According to Mike Devous, Vice President of Imaging Development at Avid Radiopharmaceuticals, recent studies suggest that Amyvid PET imaging holds promise for identifying the therapeutic window in patients with Alzheimer’s disease. This approach appears to offer higher sensitivity than MRI imaging, while maintaining comparable specificity.

Although biomarkers such as amyloid, tau protein, and neuroinflammation have played an important role in risk stratification of clinical trial populations, these methods are not yet widely used in clinical practice. Previously, with support from the U.S. National Cancer Institute, Eli Lilly and Company, and the Japan Agency for Medical Research and Development (AMED), the University of Tokyo conducted a Phase III clinical trial known as the Japanese Alzheimer’s Disease Neuroimaging Initiative (J-ADNI). This seven-year study included 537 patients. The research found that Alzheimer’s disease patients in Japan and the United States share similar disease characteristics. The trial also revealed that APOE genotyping helps predict classification within the ATN (amyloid, tau, neurodegeneration) framework.

For many years, the diagnosis of Alzheimer’s disease has been based on the hallmark presence of amyloid plaques and tau tangles in the brain, which are typically identified only after the patient’s death. According to the latest research, Eli Lilly’s P-tau217 assay can target amyloid plaques and protein tangles, providing a relatively sensitive and accurate biomarker that holds promise for earlier diagnosis of Alzheimer’s disease during the patient’s lifetime.

References:

1.Eli Lilly Designs P-Tau Biomarker Assay for Early Alzheimer’s Disease Diagnosis

2.New blood test shows great promise in the diagnosis of Alzheimer's disease.

3.Lilly's P-tau217 Blood Test Shows High Accuracy in Diagnosis of Alzheimer's Disease in Data Published in JAMA.