- Eli Lilly changed the endpoints for a Phase 3 study of its Alzheimer's drug solanezumab, the company said on Tuesday. Originally designed with two co-primary endpoints, the study will now focus solely on cognition rather than cognition and function.
- The study, called Expedition 3, is the first phase 3 study to only evaluate people with mild Alzheimer's disease (AD). Other studies have focused on patients with moderate-to-severe AD.
- Solanezumab is a monoclonal antibody which binds to amyloid beta in the brain, allowing it to be cleared from the brain before it coalesces and develops into amyloid plaques—the hallmark sign of AD found in post-mortem analysis.
Lilly's stock fell a little under 5% Tuesday as investors weighed the endpoint change. Improved function in terms of the ability to perform daily activities is an important metric for people with AD.
In explaining the move, the company cited new evidence which supports the hypothesis that cognitive decline actually precedes and predicts functional decline in patients with AD.
"It is important to note that the endpoint change affects the study's data analysis plan, but it does not affect anything related to the actual conduct of the trial," Lilly said in a statement. The company will submit trial amendments to regulators, although it recognizes regulators will continue to view both cognition and function as endpoints.
Successfully addressing the pathophysiology of AD in its early stages could potentially avert the downstream consequences of moderate-to-severe AD. The goal is to stabilize patients at the level of mild cognitive impairment, or better yet, improve their symptoms.
AD development has seen dozens of failures over the past two decades. Recently, Roche and Evotec's sembragiline failed to demonstrate cognitive improvement after 52 weeks. The last AD drug to be approved was Forest Labs' Namenda in 2003. (Namenda is now owned by Allergan).
The FDA has signaled a willingness to work with companies developing AD drugs to create an accelerated pathway. If Lilly is able to push solanezumab across the finish line, additional follow-up studies would likely be required to assess and confirm the link with function.