Trials of Once-Promising BACE Inhibitor for Alzheimer's Have Halted

“Virtually no chance of finding a positive clinical effect.”

Pharma giant Merck delivered the news yesterday in a press release that the EPOCH study, a phase 2 and 3 clinical trial evaluating the efficacy of verubecestat in those with moderate Alzheimer’s disease, will no longer continue.

An interim assessment of the trial by the external Data Monitoring Committee (eDMC) recommended its discontinuation, saying that there was “virtually no chance of finding a positive clinical effect.” They saw no issue in continuing the APECS study, evaluating the drug in those with prodromal Alzheimer’s, which will continue.

Verubecestat is a BACE inhibitor, in the words of the release: “an investigational small molecule inhibitor of the beta-site amyloid precursor protein cleaving enzyme 1 (BACE1).” BACE inhibitors had been theorized to prevent amyloid buildup in the brain, an element of the disease’s signature “plaques and tangles.” When the trials were getting underway in 2013, Merck executives believed the work had the potential to confirm or disprove the theory.

The answer to that query remains, for now, on hold, though some see this news as a damper to its merit.

Quoted in Bloomberg, James Hendrix of the Alzheimer’s Association points to the stage of the drug’s application in the trial (those already with mild-to-moderate manifestations of the condition) as its failing: “BACE isn’t going to do anything about the plaques that are already there. Maybe if you can go in before there is a lot of plaque buildup in the brain, that’s where you will have the most benefit.”

At a time, verubecestat was seen as a potential billion-dollar blockbuster. Competitors are still seeking to find gold in BACE, with collaborations from AstraZeneca and Eli Lilly, Biogen and Eisai, and Amgen and Novartis at various stages of development and testing.