Merck Inc completes enrollment in Phase III trial for MK 8931 (verubecestat)as a treatment for Alzheimers disease.

Merck confirmed the completion of enrollment for the EPOCH trial, a Phase II/III randomized, placebo-controlled, parallel-group, double-blind study of verubecestat, formerly known as MK-8931, the company’s investigational oral small molecule selective beta secretase (BACE1) inhibitor, in patients with mild-to-moderate Alzheimer’s disease .

The ongoing study commenced in November 2012, completed enrollment in the fourth quarter of 2015 and is estimated to reach primary trial completion in July 2017.

Comment: Both the AstraZeneca (AZD 3293) and Merck medicines (MK 8931) work by blocking an enzyme called beta secretase that is involved in production of beta-amyloid, a protein that creates brain plaques considered a major cause of Alzheimer's disease.The amyloid theory has been severely questioned. BMS announced that it had dropped its gamma secretase inhibitor avagacestat, sending it to join Lilly's similar product semagacestat, which was discontinued at Phase III in 2010. Both products appeared to be associated with "cognitive worsening".The beta-amyloid hypothesis is coming under question, as the relationship between amyloid and Alzheimer's symptoms is still not clear and affected by the discontinuation of August 2015 of bapineuzumab and the mixed Phase III data for solanezumab. Both these products are humanized monoclonals targeting beta amyloid.

Comment:-Data presented at AAIC 2015 showed that patients on solanezumab from the start did better than those on placebo so there are benefits starting treatment as early as possible.The EXPEDITION 3 trial will give a clearer view when it reports in 2016.