Alzheimer's disease remains one of the most vexing diseases to decipher. On Thursday, Biogen (BIIB 2.29%) announced it is shuttering its high-profile, late-stage aducanumab study. It's a massive disappointment. After reporting intriguing phase 1 data for the drug in 2014, Biogen decided to skip over smaller, phase 2 studies altogether, advancing aducanumab into a large phase 3 study it hoped could earn Food and Drug Administration (FDA) approval.
The latest in a long line of failures
Biogen was studying aducanumab in Alzheimer's disease patients with mild cognitive impairment and mild dementia. A human monoclonal antibody drug, aducanumab is designed to break down beta amyloid plaques that can build up in the brain, potentially interfering with communication between brain cells.
In its early-stage study, aducanumab demonstrated an ability to reduce these buildups. However, the relationship between beta amyloid and Alzheimer's disease progression doesn't appear to be as strong as initially thought. After independent monitors conducted an interim futility analysis of the phase 3 study, they recommended to Biogen and its licensing partner, Eisai, that the study be stopped.
Their recommendation wasn't because of any concerns over the drug's safety. Instead, it was based entirely on the recognition that the trials "were unlikely to meet their primary endpoint upon completion." The study's primary endpoint was the demonstration of improvement in cognitive and functional impairment based on the Clinical Dementia Rating-Sum of Boxes (CDR-SB) score compared to a placebo.
Aducanumab's inability to outperform placebo in this large study is yet another black mark for Alzheimer's disease drug development. Historically, 99% of the Alzheimer's disease drugs that have entered human clinical studies have ended up in laboratory dustbins rather than on pharmacy shelves.
It also may serve as the final blow to targeting amyloid plaques. Drugs seeking to disrupt amyloid plaques to slow Alzheimer's disease have been failing in late-stage clinical trials for years. The long list of disappointments includes Pfizer and J&J's bapineuzumab and Eli Lilly's solanezumab.
Check out the latest earnings call transcript for Biogen.
A major need for new approaches
A larger, longer-living population is increasing the number of people with Alzheimer's disease. As a result, it's estimated that more than 7 million Americans will be diagnosed with Alzheimer's disease by 2025, up from about 5.4 million people in 2016. Only one out of 244 potential Alzheimer's disease drugs entering clinical trials between 2002 and 2012 succeeded, and this latest failure suggests that researchers remain far away from cracking the code on what causes this disease or how to slow it.
Companies like Biogen that have made significant investments in researching this disease have suffered significant setbacks, but research is likely to continue given the size of the market opportunity. It's anyone's guess what treatment will eventually succeed at slowing Alzheimer's disease. Sadly, it won't be Biogen's aducanumab.