Merck & Co. announced that it will halt a Phase II/III study investigating the BACE inhibitor verubecestat in people with mild-to-moderate Alzheimer's disease after an external Data Monitoring Committee concluded that there was "virtually no chance of finding a positive clinical effect." The recommendation from the committee followed a recent interim safety analysis of the EPOCH study.
"The benefit-risk profile no longer made any sense," remarked Roger Perlmutter, president of Merck's research unit. The executive noted that although there weren't major safety issues that on their own would warrant stopping the trial, "it did not make sense to expose patients to any risk, whatever that may be, because the study would not succeed."
The trial was evaluating the efficacy and safety of two oral doses of verubecestat administered once-daily versus placebo in more than 2000 patients with mild-to-moderate Alzheimer's disease currently using standard of care treatment. The study's main efficacy goals were the change from baseline in the Alzheimer's Disease Assessment Scale Cognitive Subscale (ADAS-Cog) score, as well as the change from baseline in the Alzheimer's Disease Cooperative Study – Activities of Daily Living (ADCS-ADL) score, following 78 weeks of treatment.
Merck indicated that results from the EPOCH trial, which had been scheduled to complete around midyear, will be analysed and presented at an upcoming scientific meeting. For related analysis, read ViewPoints: Another one bites the dust in Alzheimer’s disease – but hope springs eternal.
Meanwhile, Merck noted that safety signals seen in the study "are not sufficient to warrant stopping" a second trial, called APECS, which is evaluating verubecestat in people with prodromal Alzheimer's disease. Results from the APECS study are expected in February 2019.
According to Mark Schoenebaum of Evercore ISI, analysts predict that sales of verubecestat, if approved, could reach around $1.3 billion in 2024. Commenting on the EPOCH study, Schoenebaum noted that patients weren't given imaging tests to ensure they had plaque buildup from Alzheimer's disease before they started the trial, an issue that has caused problems in rival studies. "While it remains possible that BACE inhibition may still have a place in Alzheimer's disease treatment, the failure of this study for futility will dampen investor enthusiasm for the mechanism," Schoenebaum remarked.
To read more Top Story articles, click here.