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Clinical data
Other namesMK-8931
ATC code
  • None
Legal status
Legal status
  • Investigational
CAS Number
PubChem CID
Chemical and physical data
Molar mass409.41 g·mol−1
3D model (JSmol)
  • C[C@]1(CS(=O)(=O)N(C(=N1)N)C)c2cc(ccc2F)NC(=O)c3ccc(cn3)F
  • InChI=1S/C17H17F2N5O3S/c1-17(9-28(26,27)24(2)16(20)23-17)12-7-11(4-5-13(12)19)22-15(25)14-6-3-10(18)8-21-14/h3-8H,9H2,1-2H3,(H2,20,23)(H,22,25)/t17-/m0/s1

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". 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. [10]


  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 4086426. 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
  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
  10. ^ Egan MF, Kost J, Tariot PN, Aisen PS, Cummings JL, Vellas B, et al. (May 2018). "Randomized Trial of Verubecestat for Mild-to-Moderate Alzheimer's Disease". The New England Journal of Medicine. 378 (18): 1691–1703. doi:10.1056/NEJMoa1706441. PMC 6776074. PMID 29719179.