In a rather unusual move, Eli Lilly has changed the endpoint of an ongoing Phase III trial assessing its experimental beta amyloid antibody solanezumab in patients with Alzheimer’s disease.
The original design of the EXPEDITION3 trial included co-primary endpoints measuring change to cognition and function in patients taking the drug versus placebo, but Lilly has now demoted the latter to a secondary target.
The drug giant says the move is driven by “emerging scientific evidence” supporting the notion that cognitive decline precedes and predicts functional decline in Alzheimer's disease, particularly in earlier stages of the disease, and not because it has seen any study data.
Lilly will continue to remain blinded to study data until after the database lock occurs in the fourth quarter of 2016, it said, noting that the endpoint change will not affect anything related to the actual conduct of the trial.
Interestingly, the firm stressed that it understands regulators globally will continue to view both cognitive and functional endpoints as necessary for clinical trials in people with mild Alzheimer's dementia, and that regulatory guidance has been to include these as co-primary endpoints.
This suggests that the functional endpoint remains a critical factor in whether the drug - which binds to soluble monomeric forms of amyloid beta after it is produced, allowing it to be cleared from the brain before it clumps together to form amyloid plaques - will ultimately gain approval.