Verubecestat

Source: Wikipedia, the free encyclopedia.
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
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

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.

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. ^ a b Makin S (2 November 2016). "New Alzheimer's drug clears milestone in human clinical trial". Scientific American.
  2. ^
    S2CID 54387517
    .
  3. ^
    PMID 24556009
    .
  4. S2CID 4579605
    .
  5. ^ "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. Archived from the original on 2012-07-28. Retrieved 2012-07-16.
  6. ^ 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. ^ a b 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
  8. ^ "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.
  9. ^ Barber J (13 February 2018). "Merck & Co. terminates Phase III study of verubecestat in prodromal Alzheimer's disease". FirstWord Pharma.
  10. ^ 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
  11. PMID 29719179
    .
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