MK-1167 is an investigational drug developed by Merck Sharp & Dohme (MSD) in collaboration with the University of Kansas Alzheimer's Disease Research Center. The trial is a Phase 2 study evaluating MK-1167 as an adjunctive therapy for patients with mild to moderate Alzheimer's disease dementia.
| Attribute |
Value |
| NCT Number |
NCT06721156 |
| Phase |
Phase 2 |
| Sponsor |
Merck Sharp & Dohme (MSD) |
| Collaborator |
University of Kansas Alzheimer's Disease Research Center |
| Status |
Recruiting |
| Participants |
350 |
| Study Start Date |
Expected 2025 |
| Estimated Completion |
2027 |
| Age Range |
50-85 years |
| Diagnosis |
Mild to Moderate Alzheimer's Disease |
The trial employs a randomized, double-blind, placebo-controlled design. Participants will be randomized to receive either MK-1167 at varying doses or placebo alongside standard of care therapy for Alzheimer's disease.
- Diagnosis of probable Alzheimer's disease per NIA-AA criteria
- MMSE score between 12-26 (mild to moderate dementia)
- Stable on acetylcholinesterase inhibitor or memantine therapy (if using)
- Age 50-85 years
- Able to provide informed consent or have capable legal representative
- Significant neurological disease other than AD
- Psychiatric disorder that could affect participation
- Significant medical comorbidities that would preclude study participation
- Use of investigational therapies within 30 days
The specific mechanism of MK-1167 has not been publicly disclosed. Merck has not revealed the molecular target or pathway being modulated. The development suggests a novel approach to Alzheimer's disease treatment beyond the established amyloid, tau, and neurotransmitter-based strategies.
The trial is based on emerging research suggesting novel therapeutic targets in Alzheimer's disease pathogenesis. The collaboration with the University of Kansas ADRC indicates a focus on translating basic science findings into clinical applications.
The trial is being conducted at multiple sites across the United States. Specific site locations will be listed on ClinicalTrials.gov when fully operational.
- NCT06721156 - MK-1167 in Alzheimer's Disease
- Merck Neuroscience Pipeline
- University of Kansas Alzheimer's Disease Research Center
¶ Alzheimer's Disease Treatment Landscape
¶ Current Standard of Care
The current treatment paradigm for AD includes:
-
Symptomatic Treatments
- Acetylcholinesterase inhibitors (donepezil, rivastigmine, galantamine)
- NMDA receptor antagonist (memantine)
- Combination therapy (donepezil + memantine)
-
Disease-Modifying Therapies
- Amyloid-targeting antibodies (lecanemab, donanemab)
- Recently approved (2023-2024)
- Significant controversy regarding benefit/risk
Despite recent approvals, significant unmet need remains:
- Symptomatic treatments: Modest efficacy, do not address disease progression
- Disease-modifying therapies: Associated with ARIA, limited to early disease
- Prevention: No approved therapies for pre-symptomatic stages
- Combination approaches: Not well explored in AD
AD drug development has the highest failure rate of any disease area:
- 99% failure rate for disease-modifying therapies
- Over 200 failed clinical trials
- Multiple high-profile late-stage failures
- Biological complexity: Multiple pathways involved
- Diagnostic uncertainty: Clinical diagnosis imperfect
- Biomarker limitations: Need better patient selection
- Trial duration: Long trials needed for meaningful endpoints
- Heterogeneity: Multiple disease subtypes
Merck has a long history in neuroscience drug development:
- Previous successes: Petolerant, Rebif, etc.
- Lecanemab development: Originally by Biogen, Merck involved in earlier work
- Current focus: Novel mechanisms beyond amyloid
While the specific mechanism is undisclosed, several possibilities:
-
Novel neurotransmitter targets
- Modulation of glutamate or GABA signaling
- Non-NMDA receptor approaches
-
Anti-inflammatory approaches
- Microglial modulation
- Peripheral immune system effects
-
Metabolic approaches
- Mitochondrial function
- Energy metabolism modulation
-
Synaptic plasticity enhancers
- AMPA receptor modulators
- Dendritic spine stabilization
Merck represents a larger trend:
- Beyond amyloid: Focus on complementary mechanisms
- Academic partnerships: Leveraging university research
- Precision medicine: Biomarker-driven approaches
- Multiple dose cohorts
- Randomized, placebo-controlled
- Dose-escalation or parallel design
- Mild to moderate disease: Most common for Phase 2
- Biomarker confirmation: Increasingly important
- Exclusion criteria: Manage comorbidities
- Cognitive measures: ADAS-Cog, MMSE, CDR
- Clinical global: CIBIC+, CGI-C
- Functional: ADL, FAQ
- Biomarkers: CSF, imaging
- Brain volumes: MRI measures
- Quality of life: QoL-AD
- Biomarker targets: Target engagement
- Sample size: 350 is moderate for Phase 2
- Duration: 2-year timeline suggests meaningful endpoints
- Power: Designed to detect moderate effects
-
Tau-targeted therapies
- Anti-tau antibodies
- Small molecule inhibitors
- Tau aggregation inhibitors
-
Neuroprotection
- Mitochondrial protectors
- Antioxidants
- Neurotrophic factors
-
Immune modulation
- Microglial modulators
- Peripheral immune approaches
- TREM2 targeting
-
Metabolic interventions
- GLP-1 analogs
- Metabolic enhancers
The field is moving toward:
- Biomarker-driven selection: Amyloid-positive, tau-positive
- Genetic subtypes: APOE, other genetic variants
- Endophenotypes: Different biological subtypes
- Combination therapies: Multi-target approaches
¶ Regulatory Landscape
- Lecamab (Leqembi): Accelerated approval, full approval
- Donanemab (Kisunla): Conditional approval
- Aduhelm: Withdrawn from market
- Regulatory flexibility: More open to novel mechanisms
- Endpoint evolution: Accepting biomarker endpoints
- Conditional approval: Possible with limited efficacy
The adjunctive approach makes sense because:
- Standard of care: Builds on existing treatments
- Regulatory path: Clear comparators
- Patient population: Larger pool than monotherapy
- Commercial potential: Multiple options for patients
University of Kansas ADRC partnership suggests:
- Academic expertise: Clinical trial infrastructure
- Biomarker capabilities: Advanced diagnostics
- Patient access: Regional recruitment
- Scientific input: Mechanistic guidance
- Start 2025: Expected recruitment timeline
- Completion 2027: 2-year treatment + follow-up
- Potential filing: 2028-2029 if successful
The MK-1167 trial represents:
- Novel mechanism: Merck's approach beyond amyloid
- Phase 2 design: Standard for mid-stage development
- Adjunctive approach: Building on existing therapies
- Academic collaboration: Leveraging university expertise
- Timeline: 2-year study with 350 participants
The trial adds to the growing AD pipeline and represents continued pharmaceutical industry investment in Alzheimer's disease therapeutics despite the field's challenges.