Verubecestat

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.

Verubecestat
Clinical data
Other namesMK-8931
ATC code
  • None
Legal status
Legal status
  • Investigational
Identifiers
  • N-{3-[(5R)-3-amino-2,5-dimethyl-1,1-dioxo-1,2,5,6-tetrahydro-1λ6,2,4-thiadiazin-5-yl]-4-fluorophenyl}-5-fluoropyridine-2-carboxamide
CAS Number
PubChem CID
ChemSpider
UNII
KEGG
CompTox Dashboard (EPA)
Chemical and physical data
FormulaC17H17F2N5O3S
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
  • Key:YHYKUSGACIYRML-KRWDZBQOSA-N

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