Alzheimer's drug trial abandoned due to lack of efficacy

In a blow to sufferers of dementia and their families, pharmaceutical company MSD (known as Merck in North America) has ended its phase 2/3 study evaluating the drug verubecestat in patients with mild to moderate forms of Alzheimer’s disease (AD). The news comes less than three months after fellow pharma company Eli Lilly announced that a clinical trial of its own key Alzheimer’s drug, solanezumab, failed to meet the primary endpoint.

The phase 2/3 study (known as protocol 017, or the EPOCH study) was a randomised, placebo-controlled, parallel-group, double-blind study evaluating the efficacy and safety of two oral doses of verubecestat, an investigational small molecule inhibitor of the beta-site amyloid precursor protein cleaving enzyme 1 (BACE1). Beta amyloid is widely thought to cause Alzheimer’s disease, though attempts by drug companies to block the substance in the brain have repeatedly failed.

The primary efficacy outcomes of the EPOCH study included a change from baseline in the Alzheimer’s Disease Assessment Scale Cognitive Subscale (ADAS-Cog) score, as well as a change from baseline in the Alzheimer’s Disease Cooperative Study – Activities of Daily Living (ADCS–ADL) score, following 78 weeks of treatment.

But the trial was ended this week following the recommendation of the external Data Monitoring Committee (eDMC), which assessed overall benefit/risk during a recent interim safety analysis and determined that there was “virtually no chance of finding a positive clinical effect”. A separate trial of the drug (protocol 019, or APECS), in patients with a less severe form of the disease known as prodromal AD, will continue.

Commenting on the news, Professor Bryce Vissel from the University of Technology Sydney stated that the results of the trial were “highly anticipated, not only because of hope for people with dementia, but also because, if the drug had succeeded, it would have demonstrated that beta amyloid contributes to the cause of Alzheimer’s disease”.

Professor Vissel said the news was “disappointing” and that there is no definitive answer as to why the drug may have failed. He did, however, note that this isn’t the end for beta amyloid theory, with a trial being run by pharma company Biogen showing “interesting and encouraging signs”. He added that numerous other drugs, acting against Alzheimer’s in a variety of other ways, are currently under development.

“It is my strong view that new approaches need to be developed and new directions of research need to be supported,” Professor Vissel said.

Results from EPOCH will be analysed and presented at an upcoming scientific meeting, while results from APECS are expected in February 2019.