7 December 2012. Merck announced this week that it has begun enrolling for the largest clinical trial of a β-secretase (BACE1) inhibitor in Alzheimer’s disease patients. After an initial Phase 2 arm that will assess the safety of MK-8931 in 200 people with mild to moderate AD, the company plans to follow a whopping 1,800 subjects for 18 months in the Phase 3 portion of its EPOCH trial. In this global study, AD patients will be randomized into four groups receiving 12, 40, or 60 mg of the oral compound, or a placebo tablet, once a day.
In Phase 1 studies, reported in July at the Alzheimer’s Association International Conference in Vancouver, a single 100 mg dose of MK-8931 reduced cerebrospinal fluid (CSF) Aβ40 and Aβ42 more than 90 percent in healthy volunteers, and a mathematical model developed by company scientists predicted that a 12 mg dose should halve CSF Aβ levels (see ARF conference story).
As primary endpoints, the Phase 3 trial will assess change from baseline in cognition and function using the ADAS-cog and ADCS-ADL (Activities of Daily Living) tests, respectively. In addition, the study will look for changes in Clinical Dementia Rating Scale Sum of Boxes (CDR-SB), Mini-Mental State Examination (MMSE), and Neuropsychiatric Inventory (NPI) scores, as well as several AD biomarkers—CSF total tau, brain amyloid load by PET imaging, and hippocampal volume.
The company anticipates gathering Phase 2 data by late 2013 and completing the study by 2016. Plans are in the works for a future MK-8931 trial in prodromal AD, Darryle Schoepp, head of neuroscience at Merck Research Laboratories, said in a video posted on the company’s website. Earlier this year, Eli Lilly and Company launched a Phase 2 study of its BACE1 inhibitor (LY2886721) in 129 people with mild cognitive impairment, and who tested positive for brain amyloid by PET scanning (see ARF related news story). Several other companies, including Eisai, are developing BACE1 inhibitors.—Esther Landhuis.