Another Clinical Trial Drug Bites the Dust

Another hopeful drug for treating Alzheimer’s in Phase III trials was shut down last week by pharma giant Merck, adding one more to the  impressive list of clinical failures.

And also leaving researchers scratching their heads over what really causes Alzheimer’s if the amyloid hypothesis (the idea that beta amyloid is the root cause of symptoms) is without validation.

Levels of the Beta-secretase  enzyme have been shown to be elevated in the far more common late-onset sporadic Alzheimer's . Drugs to block this enzyme (BACE inhibitors) in theory would prevent the buildup of beta-amyloid and may help slow or stop Alzheimer’s disease.

Merck is shuttering its trial for the BACE inhibitor verubecestat in mild-to-moderate Alzheimer’s after the external data monitoring committee concluded that the drug was a bust, with “virtually” no chance of success. A separate Phase III study in prodromal patients, set to read out in two years, will continue as investigators found no signs of safety issues.

BACE drugs essentially seek to interfere in the process that creates amyloid beta, a toxic protein often found in the brains of Alzheimer’s patients. As the top amyloid beta drugs like bapineuzumab and solanezumab— which sought to extract existing amyloid beta loads — ground their way to repeated failures, developers in the field turned increasingly to BACE therapies as an alternative mechanism that could provide the key to slowing this disease down.

Merck’s effort was the most advanced in the pipeline, but other drug companies are still in hot pursuit with their own persistent BACE efforts. 

Lilly recently decided to go ahead and stop its own prodromal Phase III for solanezumab after concluding that there was no logical reason to believe it could succeed after the study in patients with a mild form of the memory-wasting disease ended in disaster.

No significant new drug for Alzheimer’s has been approved in the past 14 years, despite massively expensive trials aimed at tackling the disease. 

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