Verubecestat

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Verubecestat
Verubecestat.svg
Clinical data
Synonyms MK-8931
ATC code
  • None
Legal status
Legal status
  • Investigational
Identifiers
CAS Number
PubChem CID
ChemSpider
UNII
KEGG
Chemical and physical data
Formula C17H17F2N5O3S
Molar mass 409.41 g·mol−1
3D model (JSmol)

Verubecestat (MK-8931) is an experimental drug for the treatment of Alzheimer's disease.[1] It is an inhibitor of beta-secretase 1 (BACE1).[2][3]

In April 2012 phase I clinical results were announced.[4] 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][5][6] EPOCH, was to complete data collection for the primary outcome measure by June 2017.[6] 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.[7] 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.[8][9] 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".[10]

References[edit]

  1. ^ a b Simon Makin (November 2, 2016). "New Alzheimer's drug clears milestone in human clinical trial". Scientific American. 
  2. ^ a b Forman M, Kleijn H, Dockendorf M, Palcza J, Tseng J, Canales C, et al. (2013). "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. doi:10.1016/j.jalz.2013.04.083. 
  3. ^ a b Yan R, Vassar R (March 2014). "Targeting the β secretase BACE1 for Alzheimer's disease therapy". The Lancet. Neurology. 13 (3): 319–29. doi:10.1016/S1474-4422(13)70276-X. PMC 4086426Freely accessible. PMID 24556009. 
  4. ^ "Merck presents results of a phase I clinical trial evaluating investigational BACE inhibitor MK-8931 at American Academy of Neurology". April 2012. Archived from the original on 2012-07-28. Retrieved 2012-07-16. 
  5. ^ "Efficacy and safety trial of verubecestat (MK-8931) in participants with prodromal Alzheimer's disease (MK-8931-019) (APECS)". Merck Sharp & Dohme Corp. Retrieved 16 February 2017. 
  6. ^ a b "An efficacy and safety trial of verubecestat (MK-8931) in mild to moderate Alzheimer's disease (P07738) (EPOCH)". Merck Sharp & Dohme Corp. October 2016. Retrieved 16 February 2017. 
  7. ^ "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. 14 February 2017. 
  8. ^ Barber, J. (2018). Merck & Co. terminates Phase III study of verubecestat in prodromal Alzheimer's disease. Retrieved from https://www.firstwordpharma.com/node/1542930
  9. ^ 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
  10. ^ Egan, Michael F; Kost, James; Tariot, Pierre N; Aisen, Paul S; Cummings, Jeffrey L; Vellas, Bruno; Sur, Cyrille; Mukai, Yuki; Voss, Tiffini; Furtek, Christine; Mahoney, Erin; Harper Mozley, Lyn; Vandenberghe, Rik; Mo, Yi; Michelson, David (2018). "Randomized Trial of Verubecestat for Mild-to-Moderate Alzheimer's Disease". New England Journal of Medicine. 378 (18): 1691. doi:10.1056/NEJMoa1706441. PMID 29719179.