Trial reportAlzheimer's research & therapy2019
Further analyses of the safety of verubecestat in the phase 3 EPOCH trial of mild-to-moderate Alzheimer's disease.
Trial report in Alzheimer's research & therapy, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT01739348 (A Randomized, Placebo Controlled, Parallel-Group, Double Blind Efficacy and Safety Trial of MK-8931 With a Long Term Double-Blind Extension in Subjects With Mild to Moderate Alzheimer's Disease), which is not on this map. Cited by 39 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
A Randomized, Placebo Controlled, Parallel-Group, Double Blind Efficacy and Safety Trial of MK-8931 With a Long Term Double-Blind Extension in Subjects With Mild to Moderate Alzheimer's Disease (Protocol No. MK-8931-017-10)(Also Known as SCH 900931, P07738)
Who cites it
39 citing papers in PubMed, 76 citations in OpenAlex.
- Reversibility of cognitive worsening observed with BACE inhibitor umibecestat in the Alzheimer's Prevention Initiative (API) Generation Studies.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2024Trial
- Monoclonal antibodies and small molecules: on the cutting edge of Alzheimer's disease therapy.Frontiers in cell and developmental biology · 2026Review
- New insight into Alzheimer's disease: small molecule-Aβ in the brain transport and peripheral organ clearance.Frontiers in aging · 2026Review
- BACE1 regulates sleep-wake cycle through both enzymatic and non-enzymatic actions.EMBO reports · 2026Article
- RoastedAntioxidants (Basel, Switzerland) · 2025Article
- Interactions between daily sleep-wake rhythms, γ-secretase, and amyloid-β peptide pathology point to complex underlying relationships.Biochimica et biophysica acta. Molecular basis of disease · 2025Article
- Proposed Therapeutic Strategy to Combat Alzheimer's Disease by Targeting Beta and Gamma Secretases.Current Alzheimer research · 2025Review
- Alzheimer's Disease and Vascular Dementia, Connecting and Differentiating Features.Current Alzheimer research · 2025Review
- Evaluation of hydrazone andJournal of enzyme inhibition and medicinal chemistry · 2024Article
- Contribution of amyloid deposition from oligodendrocytes in a mouse model of Alzheimer's disease.Molecular neurodegeneration · 2024Article
- Alzheimer's Disease-Related Epigenetic Changes: Novel Therapeutic Targets.Molecular neurobiology · 2024Review
- The amyloid-β peptide: Guilty as charged?Biochimica et biophysica acta. Molecular basis of disease · 2024Article
- Proteomics revealed an association between ribosome-associated proteins and amyloid beta deposition in Alzheimer's disease.Metabolic brain disease · 2024Article
- Alzheimer's Disease: A Suitable Case for Treatment with Precision Medicine?Medical principles and practice : international journal of the Kuwait University, Health Science Centre · 2024Review
- Green Synthetic Strategies and Pharmaceutical Applications of Thiazine and its Derivatives: An Updated Review.Current pharmaceutical biotechnology · 2024Review
- Genome-wide association study of abnormal elevation of ALT in patients exposed to atabecestat.BMC genomics · 2023Article
- siRNA drug delivery across the blood-brain barrier in Alzheimer's disease.Advanced drug delivery reviews · 2023Review
- BACE1 regulates expression of Clusterin in astrocytes for enhancing clearance of β-amyloid peptides.Molecular neurodegeneration · 2023Article
- The Amyloid Cascade Hypothesis in Alzheimer's Disease: Should We Change Our Thinking?Biomolecules · 2023Review
- The 5XFAD mouse model of Alzheimer's disease displays age-dependent deficits in habituation to a novel environment.Aging brain · 2023Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
13 authors at 5 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundVerubecestat, a BACE1 inhibitor that reduces Aβ levels in the cerebrospinal fluid of humans, was not effective in a phase 3 trial (EPOCH) of mild-to-moderate AD and was associated with adverse events. To assist in the development of BACE1 inhibitors, we report detailed safety findings from EPOCH.
methodsEPOCH was a randomized, double-blind, placebo-controlled 78-week trial evaluating verubecestat 12 mg and 40 mg in participants with mild-to-moderate AD diagnosed clinically. The trial was terminated due to futility close to its scheduled completion. Of 1957 participants who were randomized and took treatment, 652 were assigned to verubecestat 12 mg, 652 to verubecestat 40 mg, and 653 to placebo. Adverse events and relevant laboratory, vital sign, and ECG findings were assessed.
resultsVerubecestat 12 mg and 40 mg were associated with an increase in the percentage of participants reporting adverse events versus placebo (89 and 92% vs. 82%), although relatively few participants discontinued treatment due to adverse events (8 and 9% vs. 6%). Adverse events that were increased versus placebo included falls and injuries, suicidal ideation, weight loss, sleep disturbance, rash, and hair color change. Most were mild to moderate in severity. Treatment differences in suicidal ideation emerged within the first 3 months but did not appear to increase after 6 months. In contrast, treatment differences in falls and injuries continued to increase over time.
conclusionsVerubecestat was associated with increased risk for several types of adverse events. Falls and injuries were notable for progressive increases over time. While the mechanisms underlying the increased adverse events are unclear, they may be due to BACE inhibition and should be considered in future clinical development programs of BACE1 inhibitors.
trial registrationClinicalTrials.gov NCT01739348 , registered on 29 November 2012.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.