Merck has terminated its Phase II MK-1167-008 trial evaluating MK-1167 in patients with mild to moderate Alzheimer's disease dementia after the investigational therapy failed to meet pre-specified efficacy criteria at an interim analysis, ending development of one of the company's leading symptomatic Alzheimer's programs.
Merck Sharp & Dohme LLC confirmed the decision was not related to safety, stating the candidate "did not meet the necessary efficacy criteria to warrant further investigation." The company has publicly commented on the trial's discontinuation.
The randomized, quadruple-blind, placebo-controlled Phase II study (NCT06721156) enrolled 369 patients aged 55-90 years with Stage 4 or Stage 5 Alzheimer's disease dementia who were receiving acetylcholinesterase inhibitor therapy. Participants were randomized to receive one of three once-daily doses of MK-1167 or placebo for approximately 24 weeks.
The primary endpoint was change from baseline in the Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog11) total score at Week 24, with secondary endpoints assessing global clinical change, activities of daily living, and safety. The trial was conducted across multiple countries, including the US, Canada, Japan, South Korea, Spain, Italy, the Netherlands, the UK, and Argentina. Although primary completion was recorded on June 5, 2026, no efficacy or biomarker data have been released.
Merck said the decision followed a planned interim analysis showing the study failed to meet its efficacy threshold. While the ClinicalTrials.gov registry lists the reason for termination as "business reasons," the company said the outcome reflected lack of efficacy rather than any safety concern.
MK-1167 is a positive allosteric modulator of the alpha-7 nicotinic acetylcholine receptor (α7 nAChR), a mechanism intended to enhance cholinergic neurotransmission and improve cognitive function. Merck had previously highlighted the candidate in presentations on its neuroscience pipeline as a potential symptomatic therapy for Alzheimer's disease. Earlier Phase I data demonstrated pharmacodynamic activity in healthy volunteers, but those findings did not translate into clinical benefit in the Phase II study.