Eli Lilly and Company announced results from two distinct analyses of a phase 2 study using the tau imaging agent flortaucipir ([18F] AV-1451) that evaluated the relationship between tau tangles and the progression of Alzheimer's disease.

The first analysis, "Evolution of [18F] AV-1451 PET Tau Signal: Interim Analysis of an 18 Month Phase 2 Study," suggested the presence of tau tangles increased significantly over an 18-month period, consistent with ongoing cognitive decline in beta-amyloid positive patients. Further, patients with more tau at baseline accumulated tau at a faster rate, indicating the development of Alzheimer's disease accelerates as it progresses.1 The second analysis, "The Relationship of [18F] AV-1451 PET Tau Images to Changes in Cognition over Time," suggested a correlation between the location of tau in the brain and progression of cognitive decline in beta-amyloid positive patients. These findings were presented today at the Alzheimer's Association International Conference 2016 (AAIC 2016) in Toronto, Canada.

"These data are exciting because they suggest new insights into the relationships between tau deposits and the progression of Alzheimer's disease," said Mark Mintun, M.D., chief medical officer, Avid Radiopharmaceuticals, a wholly owned subsidiary of Lilly. "We hope these results can help guide future studies to further our understanding of the mechanisms of Alzheimer's disease and speed the development of treatments."

The primary objective of the first analysis was to characterize the rate of change in the tau signal in Alzheimer's disease to follow disease progression. The primary objective of the second analysis was to understand how the uptake patterns of flortaucipir relate to cognitive performance. Flortaucipir is Lilly's phase 3 tau positron emission tomography (PET) imaging agent, an investigational chemical entity being studied for the imaging of tau pathology. Tau imaging agents may enable researchers to noninvasively examine the degree and extent of tau pathology in the brain, quantify changes in tau deposition over time, evaluate its relation to cognition and assess the efficacy of Alzheimer's disease therapeutics. As a marker of neurodegeneration, tau imaging may serve as an adjunct tool to aid in diagnosis, as well as in disease staging. A tau-PET tracer could potentially also allow for a selection of pathology-positive individuals and monitor the effectiveness of therapy.

"This is the first time an analysis has shown a correlation between tau tangles and cognitive decline in patients living with Alzheimer's disease," said Michael Devous, Ph.D., vice president, Avid Radiopharmaceuticals, a wholly owned subsidiary of Lilly. "As tau pathology is considered a biomarker of cognitive decline, understanding the patterns in the tau signal specific to Alzheimer's disease might be useful in predicting disease progression."

Alzheimer's disease, the most common form of dementia, causes progressive decline in memory and other aspects of cognition. Beta-amyloid plaques and tau tangles are two known hallmark pathologies of Alzheimer's disease and each works in different ways. Tau protein forms into neurofibrillary tangles, which are abnormal collections of twisted protein threads found inside nerve cells. These tangles start in the areas of the brain important for memory, then proceed throughout the rest of the brain as symptoms progress.