Merck ends Phase II Alzheimer's trial of MK-1167 after interim efficacy failure

Merck has terminated its [Phase II MK-1167-008 tria](https://app.allsci.com/clinical-trial/ASC-CT-0000000051040-1.0-1745763661)l 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](https://www.fiercebiotech.com/biotech/merck-halts-ph-2-alzheimers-trial-after-neuphoria-small-molecule-underwhelms) on the trial's discontinuation. The randomized, quadruple-blind, placebo-controlled Phase II study ([NCT06721156](https://clinicaltrials.gov/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. The program was developed in partnership with Neuphoria Therapeutics, with whom Merck has collaborated since 2014. Initiation of the Phase II trial triggered a $15 million milestone payment to Neuphoria in early 2025. Merck said the broader collaboration remains in place despite discontinuation of MK-1167. The setback comes during a difficult period for Neuphoria, whose Phase III social anxiety disorder program failed in late 2025 and which is currently pursuing a proposed merger with Scancell Holdings. With MK-1167 discontinued, Merck's remaining clinical Alzheimer's asset is MK-2214, an anti-tau antibody licensed from Teijin Pharmaceutical that is currently in Phase II, with study completion expected in 2029. The failure underscores the continuing difficulty of developing effective symptomatic therapies for Alzheimer's disease despite decades of research into cholinergic targets. Although enhancing cholinergic signaling remains a biologically plausible approach, translating pharmacological activity into meaningful cognitive benefit has proven challenging, highlighting the need for new therapeutic strategies beyond established mechanisms. *** This article was generated with AI assistance and reviewed and edited by the AllSci editorial team Explore more at AllSci News: [https://allsci.com/news/](https://allsci.com/news/) --- Spot something wrong? [Report an issue with this article](https://newsgen-prod.reframedata.com/feedback/mk-1167-alzheimers-trial-merck-terminates-phase)