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- | verubecestat (MK-8931) / Merck (MSD)
Journal: Drug-induced reductions in brain amyloid-β levels may adversely affect cognition and behavior by a disruption of functional connectivity homeostasis. (Pubmed Central) - Aug 23, 2020
No abstract available
- || verubecestat (MK-8931) / Merck (MSD)
Clinical, PK/PD data, Journal: Safety, Tolerability, and Pharmacokinetics of the β-Site Amyloid Precursor Protein-Cleaving Enzyme 1 Inhibitor Verubecestat (MK-8931) in Healthy Elderly Male and Female Subjects. (Pubmed Central) - Aug 20, 2020
Verubecestat pharmacokinetics were similar between healthy elderly male and female subjects and similar to those reported in healthy young males in previous studies. These data supported subsequent studies to assess the potential efficacy of verubecestat in subjects with Alzheimer's disease.
- verubecestat (MK-8931) / Merck (MSD)
[VIRTUAL] REDUCED NON-FIBRILLAR AΒ SPECIES IN A PATIENT TREATED WITH LOW DOSES OF BACE1 INHIBITOR () - Aug 10, 2020 - Abstract #CTAD2020CTAD_179;
These data supported subsequent studies to assess the potential efficacy of verubecestat in subjects with Alzheimer's disease. Our data indicate that low-dose Verubecestat may have exerted some effect on the non-fibrillar forms of Aβ.
- verubecestat (MK-8931) / Merck (MSD)
[VIRTUAL] VOXEL BASED MORPHOMETRY REVEALS A DISTRIBUTED PATTERN OF GREY MATTER VOLUME CHANGES FOLLOWING VERUBECESTAT EXPOSURE IN THE EPOCH TRIAL () - Aug 7, 2020 - Abstract #CTAD2020CTAD_14;
GM tissue volumes are reduced in a consistent set of brain regions for both dose groups, and the effect is apparent after 13 weeks of treatment. The pattern of GM tissue reduction is most prominent in occipital and posterior brain regions, though relevant temporal, parietal and frontal features are also observed.
- sirolimus / Generic mfg.
[VIRTUAL] Quantitative systems pharmacology model of Alzheimers disease to study efficacy of combinatorial therapy on multiple pathology components () - Aug 2, 2020 - Abstract #AAIC2020AAIC_3332;
Multiple in vitro data for intracellular dynamics perturbations (rapamycin, proteasome inhibitors, vinblastine) available from the literature were used to estimate the intracellular regulation parameters...Data from clinical studies for immunotherapy (BAN2401) and BACE inhibitor (verubecestat) have been used for retrospective model validation, together with data for treatment by rapamycin, calpain inhibitors, proteasome activation in mouse AD models... QSP modeling allows for choice of combinations of newly emerging biologics combined with targeting cell metabolism, to lead optimization and increase of treatment efficacy.
- verubecestat (MK-8931) / Merck (MSD)
[VIRTUAL] Pharmacokinetic, Pharmacodynamics, and Transcriptomics Analysis of Verubecestat Treatment in 5XFAD mice () - Aug 2, 2020 - Abstract #AAIC2020AAIC_1709;
Moreover, VER failed to improve cognitive behavior in 5XFAD mice, in line with the lack of cognitive improvement in patients. Together these data positive support for pipeline validation of the MODEL-AD PTC, and highlight the importance for post-treatment transcriptomics to align model systems with drug mechanism of actions.
- ||| verubecestat (MK-8931) / Merck (MSD)
Clinical, P3 data, Journal: Further analyses of the safety of verubecestat in the phase 3 EPOCH trial of mild-to-moderate Alzheimer's disease. (Pubmed Central) - Jul 18, 2020
P2/3
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.
- | Xtandi (enzalutamide) / Pfizer, Astellas, verubecestat (MK-8931) / Merck (MSD)
Journal: Application of molecular framework-based data-mining method in the search for beta-secretase 1 inhibitors through drug repurposing. (Pubmed Central) - Jul 9, 2020
The compounds that afforded the best binding energies were DB06925 (tyrosine-protein kinase inhibitor), DB12285 (Verubecestat) and DB08899 (Enzalutamide). Moreover, docking results indicated several other molecules with high in silico inhibitory potency that can be further studied for developing a potential treatment for Alzheimer's disease.
- || verubecestat (MK-8931) / Merck (MSD)
Clinical, Journal: Biowaiver Applications in Support of a Polymorph During Late-Stage Clinical Development of Verubecestat-Current Challenges and Future Opportunities for Global Regulatory Alignment. (Pubmed Central) - Jul 3, 2020
The data presented in this manuscript provide a compelling case for adjustments to the current draft ICH M9 guidance which provides recommendations for biowaiver applications. Specifically, this manuscript contains recommendations with respect to API attributes, selection of dissolution media and apparatus, and methods to assess dissolution similarity if needed, which should be considered for inclusion in a science- and risk-based global guidance document to benefit patients, regulators, and the pharmaceutical industry.
- | verubecestat (MK-8931) / Merck (MSD)
Journal: Investigation of Intermolecular interactions and Stability of Verubecestat in the active site of BACE1: Development of First model from QM/MM based Charge density and MD Analysis. (Pubmed Central) - Jun 27, 2020
The Molecular dynamics simulation has been performed, which confirms the high stability and compactness of verubecestat in the active site of BACE1. The MM-GBSA and MM-PBSA free energy calculations of verubecestat-BACE1 also confirm the high binding affinity of verubecestat.
- || verubecestat (MK-8931) / Merck (MSD)
PK/PD data, Preclinical, Journal: Quantification and pharmacokinetic property of verubecestat an BACE1 inhibitor in rat plasma. (Pubmed Central) - Feb 26, 2020
Matrix effect, extraction recovery, and stability data were in line with the standard FDA guidelines for validating a bioanalytical method. The validity of the developed method was confirmed through the pharmacokinetic study.
- || verubecestat (MK-8931) / Merck (MSD)
Clinical, PK/PD data, Journal: Pharmacokinetics and Pharmacodynamics of the BACE1 Inhibitor Verubecestat (MK-8931) in Healthy Japanese Adults: a Randomized, Placebo-Controlled Study. (Pubmed Central) - Feb 16, 2020
Verubecestat also reduced mean cerebrospinal fluid concentrations of the β-amyloid proteins Aβ40, Aβ42, and sAPPβ; the level of reduction was comparable between Japanese and non-Japanese subjects. These results support the continued global development of verubecestat as a potential disease-modifying agent for Japanese and non-Japanese subjects who are at-risk for developing AD.
- | verubecestat (MK-8931) / Merck (MSD)
Journal: Lessons that can be learnt from the failure of verubecestat in Alzheimer's disease. (Pubmed Central) - Jan 10, 2020
In my opinion, the failure of verubecestat in EPOCH and APECS probably could have been avoided if a safety and potential efficacy trial (phase 2) had been completed prior to starting phase 3. It seems to me that, as we have a poor understanding of the underlying mechanisms/cause of Alzheimer's disease, this is where the research emphasis should be, not phase 3 clinical trials.
- verubecestat (MK-8931) / Merck (MSD)
NEURAL INJURY BIOMARKER PROFILES FROM THE EPOCH PHASE 3 TRIAL OF VERUBECESTAT IN PATIENTS WITH MILD-TO-MODERATE ALZHEIMER’S DISEASE. () - Oct 20, 2019 - Abstract #CTAD2019CTAD_216;
P2/3
Disclosures: Funding for this research was provided by Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA. MEK, CS, JK, DP, CF, JS, ND, RC, and MFE are current or former employees of Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA, and may own stock and/or stock options in Merck & Co., Inc., Kenilworth, NJ, USA.
- verubecestat (MK-8931) / Merck (MSD)
Verubecestat-Induced Brain Volume Loss Occurs Rapidly and Only in Amyloid-Enriched Brain Regions in EPOCH, a Phase 3 Trial in Mild-To-Moderate Alzheimers Disease Patients (Floridian Ballroom) - Oct 17, 2019 - Abstract #ACNP2019ACNP_179;
P2/3
Verubecestat did not appear to increase neurodegeneration as assessed by neurofilament light chain. These results suggest that verubecestat is not associated with a generalized, widespread or progressive neurotoxic effect but may exert specific effects on amyloid related processes.
- ALZHEIMER’S PREVENTION INITIATIVE GENERATION PROGRAM: UPDATE AND NEXT STEPS () - Oct 16, 2019 - Abstract #CTAD2019CTAD_60;
Results from the Generation Program will be analyzed including follow-up visits o -treatment to evaluate the potential reversal of the observed early worsening of cognitive measures. Trial findings, data, biological samples, and motivated amyloid-positive and -negative participants will provide important resources for the advancement of AD prevention research.
- verubecestat (MK-8931) / Merck (MSD)
Modeling of verubecestat Ph3 PK/PD data against to amyloid PET () - Oct 16, 2019 - Abstract #CTAD2019CTAD_50;
2) To what could still be done non-clinically to understand if anything would have predicted the adverse effects. Michael F. EGAN (1), Michael IRIZARRY (2), John SIMS (3), Craig SHERRING (4) ((1) Merck, USA, (2) Eisai, USA, (3) Eli Lilly & Co., USA, (4) AstraZeneca, USA)
- | verubecestat (MK-8931) / Merck (MSD), solanezumab (LY2062430) / Eli Lilly
Clinical, Journal: Impact of amyloid-beta changes on cognitive outcomes in Alzheimer's disease: analysis of clinical trials using a quantitative systems pharmacology model. (Pubmed Central) - Sep 18, 2019
Michael F. EGAN (1), Michael IRIZARRY (2), John SIMS (3), Craig SHERRING (4) ((1) Merck, USA, (2) Eisai, USA, (3) Eli Lilly & Co., USA, (4) AstraZeneca, USA) If these predictions are confirmed in post-hoc analyses of failed clinical amyloid-modulating trials, one should question the rationale behind testing these interventions in early and prodromal subjects with low or zero amyloid load.
- | verubecestat (MK-8931) / Merck (MSD)
Journal: Verubecestat for Prodromal Alzheimer's Disease. (Pubmed Central) - Jul 29, 2019
If these predictions are confirmed in post-hoc analyses of failed clinical amyloid-modulating trials, one should question the rationale behind testing these interventions in early and prodromal subjects with low or zero amyloid load. No abstract available
- | verubecestat (MK-8931) / Merck (MSD)
Journal: Verubecestat for Prodromal Alzheimer's Disease. Reply. (Pubmed Central) - Jul 29, 2019
No abstract available No abstract available
- | verubecestat (MK-8931) / Merck (MSD)
Clinical, Clinical Trial,Phase I, Clinical Trial,Phase II, Clinical Trial,Phase III, Journal: Randomized Trial of Verubecestat for Prodromal Alzheimer's Disease. (Pubmed Central) - Apr 28, 2019
P3
Verubecestat did not improve clinical ratings of dementia among patients with prodromal Alzheimer's disease, and some measures suggested that cognition and daily function were worse among patients who received verubecestat than among those who received placebo. (Funded by Merck Sharp & Dohme; ClinicalTrials.gov number, NCT01953601.).
- |||| verubecestat (MK-8931) / Merck (MSD)
Researchers publish study findings of the halted Phase III #Alzheimer’s disease #drug trial on #verubecestat @NEJM @MerceBoadaR https://t.co/z0LJgHb0UP (Twitter) - Apr 15, 2019
- |||| verubecestat (MK-8931) / Merck (MSD)
Clinical: Added to⚡️ “Another failed clinical trial: Verubecestat makes #Alzheimers worse.” by @DashGenomics - What can we learn from this failure? - Comments from KOLs. https://t.co/vAGSTVLfu5 … +++++++ (Twitter) - Apr 14, 2019
- |||| verubecestat (MK-8931) / Merck (MSD)
Clinical: Added to⚡️ “Another failed clinical trial: Verubecestat makes #Alzheimers worse.” by @DashGenomics - What can we learn from this failure? - Comments from KOLs. https://t.co/vAGSTVLfu5 +++++++ (Twitter) - Apr 14, 2019
- |||| verubecestat (MK-8931) / Merck (MSD)
Clinical: Another drug fails for Dementia. Verubecestat did not improve clinical ratings of dementia among patients with prodromal Alzheimer’s disease, and some measures suggested that impaired cognition and daily function @NEJM https://t.co/c1c1UXPsim (Twitter) - Apr 11, 2019
- ||||| verubecestat (MK-8931) / Merck (MSD)
Clinical: BACE inhibitor verubacestat appears to worsen cognition! We desperately need new thinking and support to explore new ideas.. Randomized Trial of Verubecestat for Prodromal Alzheimer’s Disease | NEJM https://t.co/FAX0s7LsnW (Twitter) - Apr 11, 2019
- | verubecestat (MK-8931) / Merck (MSD)
Trial termination: APECS: Efficacy and Safety Trial of Verubecestat (MK-8931) in Participants With Prodromal Alzheimer's Disease (MK-8931-019) (clinicaltrials.gov) - Apr 24, 2018
P3, N=1454, Terminated, Sponsor: Merck Sharp & Dohme Corp.
(Funded by Merck Sharp & Dohme; ClinicalTrials.gov number, NCT01953601.). Active, not recruiting --> Terminated
- |||| verubecestat (MK-8931) / Merck (MSD)
Trial completion date, Trial primary completion date: APECS: Efficacy and Safety Trial of Verubecestat (MK-8931) in Participants With Prodromal Alzheimer's Disease (MK-8931-019) (clinicaltrials.gov) - Mar 30, 2018
P3, N=1350, Active, not recruiting, Sponsor: Merck Sharp & Dohme Corp.
Active, not recruiting --> Terminated Trial completion date: Mar 2021 --> Apr 2018 | Trial primary completion date: Feb 2019 --> Apr 2018
- | verubecestat (MK-8931) / Merck (MSD)
Trial completion, Enrollment change, Trial primary completion date: An Open-Label Study Investigating MK-8931 in Participants With Mild and Moderate Hepatic Insufficiency (MK-8931-016) (clinicaltrials.gov) - May 12, 2017
P1, N=16, Completed, Sponsor: Merck Sharp & Dohme Corp.
Trial completion date: Mar 2021 --> Apr 2018 | Trial primary completion date: Feb 2019 --> Apr 2018 Recruiting --> Completed | N=32 --> 16 | Trial primary completion date: Jul 2017 --> Apr 2017
- verubecestat (MK-8931) / Merck (MSD)
Trial primary completion date: An Open-Label Study Investigating MK-8931 in Participants With Mild and Moderate Hepatic Insufficiency (MK-8931-016) (clinicaltrials.gov) - May 1, 2017
P1, N=32, Recruiting, Sponsor: Merck Sharp & Dohme Corp.
Recruiting --> Completed | N=32 --> 16 | Trial primary completion date: Jul 2017 --> Apr 2017 Trial primary completion date: Apr 2017 --> Jul 2017
- | verubecestat (MK-8931) / Merck (MSD)
Trial termination: EPOCH: An Efficacy and Safety Trial of Verubecestat (MK-8931) in Mild to Moderate Alzheimer's Disease (P07738) (clinicaltrials.gov) - Apr 27, 2017
P2/3, N=2210, Terminated, Sponsor: Merck Sharp & Dohme Corp.
Trial primary completion date: Apr 2017 --> Jul 2017 Active, not recruiting --> Terminated
- |||| verubecestat (MK-8931) / Merck (MSD)
Trial primary completion date: EPOCH: An Efficacy and Safety Trial of Verubecestat (MK-8931) in Mild to Moderate Alzheimer's Disease (P07738) (clinicaltrials.gov) - Mar 14, 2017
P2/3, N=2221, Active, not recruiting, Sponsor: Merck Sharp & Dohme Corp.
Active, not recruiting --> Terminated Trial primary completion date: Jun 2017 --> Mar 2017
- ||||| verubecestat (MK-8931) / Merck (MSD)
Enrollment closed: APECS: Efficacy and Safety Trial of Verubecestat (MK-8931) in Participants With Prodromal Alzheimer's Disease (MK-8931-019) (clinicaltrials.gov) - Nov 23, 2016
P3, N=1500, Active, not recruiting, Sponsor: Merck Sharp & Dohme Corp.
Trial primary completion date: Jun 2017 --> Mar 2017 Recruiting --> Active, not recruiting
- verubecestat (MK-8931) / Merck (MSD)
Enrollment open: An Open-Label Study Investigating MK-8931 in Participants With Mild and Moderate Hepatic Insufficiency (MK-8931-016) (clinicaltrials.gov) - Oct 25, 2016
P1, N=32, Recruiting, Sponsor: Merck Sharp & Dohme Corp.
Recruiting --> Active, not recruiting Not yet recruiting --> Recruiting
- | verubecestat (MK-8931) / Merck (MSD)
New P1 trial: An Open-Label Study Investigating MK-8931 in Participants With Mild and Moderate Hepatic Insufficiency (MK-8931-016) (clinicaltrials.gov) - Sep 22, 2016
P1, N=32, Not yet recruiting, Sponsor: Merck Sharp & Dohme Corp.
- ||||| verubecestat (MK-8931) / Merck (MSD)
Enrollment closed: EPOCH: An Efficacy and Safety Trial of Verubecestat (MK-8931) in Mild to Moderate Alzheimer's Disease (P07738) (clinicaltrials.gov) - Nov 10, 2015
P2/3, N=1960, Active, not recruiting, Sponsor: Merck Sharp & Dohme Corp.
Not yet recruiting --> Recruiting Recruiting --> Active, not recruiting
- |||| verubecestat (MK-8931) / Merck (MSD)
Trial primary completion date: APECS: Efficacy and Safety Trial of Verubecestat (MK-8931) in Participants With Prodromal Alzheimer's Disease (MK-8931-019) (clinicaltrials.gov) - Nov 1, 2015
P3, N=1500, Recruiting, Sponsor: Merck Sharp & Dohme Corp.
Recruiting --> Active, not recruiting Trial primary completion date: Mar 2018 --> Jul 2019
- |||| verubecestat (MK-8931) / Merck (MSD)
Trial primary completion date: EPOCH: An Efficacy and Safety Trial of Verubecestat (MK-8931) in Mild to Moderate Alzheimer's Disease (P07738) (clinicaltrials.gov) - Feb 23, 2015
P2/3, N=1960, Recruiting, Sponsor: Merck Sharp & Dohme Corp.
Trial primary completion date: Mar 2018 --> Jul 2019 Trial primary completion date: Apr 2017 --> Jul 2017
- |||||| verubecestat (MK-8931) / Merck (MSD)
Enrollment open: APECS: Efficacy and Safety Trial of Verubecestat (MK-8931) in Participants With Prodromal Alzheimer's Disease (MK-8931-019) (clinicaltrials.gov) - Nov 18, 2013
P3, N=1500, Recruiting, Sponsor: Merck Sharp & Dohme Corp.
Trial primary completion date: Apr 2017 --> Jul 2017 Not yet recruiting --> Recruiting
- |||||||||| verubecestat (MK-8931) / Merck (MSD)
New P3 trial: APECS: Efficacy and Safety Trial of Verubecestat (MK-8931) in Participants With Prodromal Alzheimer's Disease (MK-8931-019) (clinicaltrials.gov) - Sep 29, 2013
P3, N=1500, Recruiting, Sponsor: Merck Sharp & Dohme Corp.
- |||||| verubecestat (MK-8931) / Merck (MSD)
Enrollment open: EPOCH: An Efficacy and Safety Trial of Verubecestat (MK-8931) in Mild to Moderate Alzheimer's Disease (P07738) (clinicaltrials.gov) - Dec 3, 2012
P2/3, N=1960, Recruiting, Sponsor: Merck Sharp & Dohme Corp.
Not yet recruiting --> Recruiting Not yet recruiting --> Recruiting
- |||||||||| verubecestat (MK-8931) / Merck (MSD)
New P2/3 trial: EPOCH: An Efficacy and Safety Trial of Verubecestat (MK-8931) in Mild to Moderate Alzheimer's Disease (P07738) (clinicaltrials.gov) - Nov 29, 2012
P2/3, N=1960, Recruiting, Sponsor: Merck Sharp & Dohme Corp.
- verubecestat (MK-8931) / Merck (MSD)
Enrollment change: A Two-Part, Single-Dose Study of the Pharmacokinetics of MK-8931 in Subjects With Renal Insufficiency (MK-8931-009 [P08535]) (clinicaltrials.gov) - Nov 19, 2012
P1, N=12, Completed, Sponsor: Merck Sharp & Dohme Corp.
Not yet recruiting --> Recruiting N=36 --> 12
- | verubecestat (MK-8931) / Merck (MSD)
Trial completion: A Two-Part, Single-Dose Study of the Pharmacokinetics of MK-8931 in Subjects With Renal Insufficiency (MK-8931-009 [P08535]) (clinicaltrials.gov) - Nov 19, 2012
P1, N=12, Completed, Sponsor: Merck Sharp & Dohme Corp.
N=36 --> 12 Active, not recruiting --> Completed
- verubecestat (MK-8931) / Merck (MSD)
Trial completion: A Study of the Safety, Tolerability, and Pharmacodynamics of MK-8931 in Participants With Alzheimer's Disease (MK-8931-010 AM1 [P07820 AM1]) (clinicaltrials.gov) - Jul 12, 2012
P1, N=32, Completed, Sponsor: Merck
Active, not recruiting --> Completed Active, not recruiting --> Completed
- | verubecestat (MK-8931) / Merck (MSD)
New P1 trial: A Two-Part, Single-Dose Study of the Pharmacokinetics of MK-8931 in Subjects With Renal Insufficiency (MK-8931-009 [P08535]) (clinicaltrials.gov) - Feb 21, 2012
P1, N=12, Completed, Sponsor: Merck Sharp & Dohme Corp.
- verubecestat (MK-8931) / Merck (MSD)
New P1 trial: A Study of the Safety, Tolerability, and Pharmacodynamics of MK-8931 in Participants With Alzheimer's Disease (MK-8931-010 AM1 [P07820 AM1]) (clinicaltrials.gov) - Dec 19, 2011
P1, N=32, Completed, Sponsor: Merck