Chemistry:Verubecestat
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| Other names | MK-8931 |
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| Formula | C17H17F2N5O3S |
| Molar mass | 409.41 g·mol−1 |
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Verubecestat (MK-8931) was an experimental drug for the treatment of Alzheimer's disease.[1] It is an inhibitor of beta-secretase 1 (BACE1),[2][3][4] which, after initial promise proved disappointing.
In April 2012 phase I clinical results were announced.[5] Phase 1b results have also been reported.[3][2]
(As of December 2016) it was in two phase 2/3 clinical trials that have progressed to phase 3.[1][6][7] EPOCH, was to complete data collection for the primary outcome measure by June 2017.[7] However, in February 2017 Merck halted its late-stage trial of verubecestat for mild to moderate Alzheimer's disease after it was reported as having "virtually no chance of finding a positive clinical effect" according to an independent panel of experts.[8] The results of Merck's trial of verubecestat on patients with prodromal (early stage) Alzheimer's were expected in February 2019. However, the trial was terminated in February 2018, after a data monitoring committee concluded it was unlikely that the drug would show a positive benefit/risk ratio.[9][10] The final conclusion was that "verubecestat did not reduce cognitive or functional decline in patients with mild-to-moderate Alzheimer’s disease and was associated with treatment-related adverse events". Verubecestat was projected to be a breakthrough medicine for dementia related illness, however it is still unknown why the medicine was not effective in humans. [11]
References
- ↑ 1.0 1.1 "New Alzheimer's drug clears milestone in human clinical trial". Scientific American. 2 November 2016. https://www.scientificamerican.com/article/new-alzheimer-s-drug-clears-milestone-in-human-clinical-trial1.
- ↑ 2.0 2.1 "The novel BACE inhibitor MK-8931 dramatically lowers CSF beta-amyloid in patients with mild-to-moderate Alzheimer's disease". Alzheimer's & Dementia 9 (4): P139. 2013. doi:10.1016/j.jalz.2013.04.083.
- ↑ 3.0 3.1 "Targeting the β secretase BACE1 for Alzheimer's disease therapy". The Lancet. Neurology 13 (3): 319–329. March 2014. doi:10.1016/S1474-4422(13)70276-X. PMID 24556009.
- ↑ "The BACE1 inhibitor verubecestat (MK-8931) reduces CNS β-amyloid in animal models and in Alzheimer's disease patients". Science Translational Medicine 8 (363): 363ra150. November 2016. doi:10.1126/scitranslmed.aad9704. PMID 27807285.
- ↑ "Merck presents results of a phase I clinical trial evaluating investigational BACE inhibitor MK-8931 at American Academy of Neurology". Merck Sharp & Dohme Corp.. April 2012. http://www.merck.com/newsroom/news-release-archive/research-and-development/2012_0427.html.
- ↑ Clinical trial number NCT01953601 for "Efficacy and safety trial of verubecestat (MK-8931) in participants with prodromal Alzheimer's disease (MK-8931-019) (APECS)" at ClinicalTrials.gov
- ↑ 7.0 7.1 Clinical trial number NCT01739348 for "An efficacy and safety trial of verubecestat (MK-8931) in mild to moderate Alzheimer's disease (P07738) (EPOCH)" at ClinicalTrials.gov
- ↑ "Merck announces EPOCH study of verubecestat for the treatment of people with mild to moderate Alzheimer's disease to stop for lack of efficacy" (Press release). Merck Sharp & Dohme Corp. 14 February 2017.
- ↑ "Merck & Co. terminates Phase III study of verubecestat in prodromal Alzheimer's disease.". FirstWord Pharma. 13 February 2018. https://www.firstwordpharma.com/node/1542930.
- ↑ Clinical trial number NCT01953601 for "Efficacy and Safety Trial of Verubecestat (MK-8931) in Participants With Prodromal Alzheimer's Disease (MK-8931-019)" at ClinicalTrials.gov
- ↑ "Randomized Trial of Verubecestat for Mild-to-Moderate Alzheimer's Disease". The New England Journal of Medicine 378 (18): 1691–1703. May 2018. doi:10.1056/NEJMoa1706441. PMID 29719179.
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