Questions over future of Alzheimer's research as more major human drug trials fail
Pharmaceutical giant Roche has announced it is discontinuing two major human clinical trials into the anti-Alzheimer's drug crenezumab. The decision by Roche to pull the plug on the trials comes after many similar treatments have also recently failed in human trials adding to the growing doubt about how to best tackle Alzheimer's disease.
Crenezumab is an experimental drug designed to bind to, and effect the removal of, amyloid-beta proteins in the brain. It is commonly believed that the aggregation of these amyloid-beta proteins, into what are called plaques, is the primary pathogenic cause of Alzheimer's disease, so the vast majority of current research is working to find ways to dissolve those toxic accumulations in the brain.
In 2015, crenezumab moved into the final stage of human clinical trials, after moderately successful prior trials proved the drugs safety, and potential. This phase 3 trial, dubbed CREAD, was set to run until 2021, however, an interim analysis of the results so far recently concluded the drug, while safe, "was unlikely to meet the primary endpoint of change from baseline in Clinical Dementia Rating-Sum of Boxes (CDR-SB) Score."
"While the results with crenezumab are disappointing, they meaningfully contribute to our understanding of Alzheimer's disease," says Sandra Horning, Chief Medical Officer and Head of Global Product Development at Roche. "We gratefully acknowledge the participants in the CREAD trials and the efforts of everyone involved in this important programme."
One trial for crenezumab is still underway, focusing on a cohort of healthy subjects with a specific genetic mutation making them at high risk of developing familial Alzheimer's disease. Roche is also involved in two other major investigational trials into prospective Alzheimer's drugs. One, called gantenerumab, targets amyloid-beta proteins, albeit using a different mechanism of action from crenezumab. The other is called RG6100, and it targets the accumulation of tau, another toxic protein target often implicated in Alzheimer's disease pathology.
This latest announcement from Roche comes after a long string of similar human clinical trial failures into Alzheimer's disease treatments. Last year, pharma giant Merck announced the discontinuation of a phase 3 trial into a drug targeting amyloid-beta proteins due to ineffective results, while another big company, Pfizer, completely pulled out of all research into Alzheimer's early in 2018 due to constant trial failures.
Despite this dispiriting run of clinical trail failures, researchers in the field are not losing all hope. Some longstanding advocates of the amyloid-beta hypothesis are suggesting the toxic protein is still a good target for research but new approaches in how to combat its aggregations are necessary.
Other researchers are shooting off into a variety of different directions claiming the amyloid hypothesis has so continually failed that new ideas must be investigated. Everything from the herpes virus to gum disease bacteria are being floated as avenues for investigation, so while this clinical trial failure is certainly disappointing, it is by no means the end of the line for scientists working to find ways to fight back against this terrible neurodegenerative disease.