letermovir

Trade name: prevymis

Small moleculeapprovedOrphan Drug FDAFast Track FDABreakthrough Therapy FDA

Approved

Nov 8, 2017

Letermovir (AIC246 or MK-8228), a 3,4-dihydro-quinazoline- 4-yl-acetic acid derivative, is the prototype viral terminase complex inhibitor that is most advanced in its clinical development. The novel compound was initially developed by AiCuris. In April 2011, the drug was granted orphan drug designation for prevention of CMV disease by the European Commission. In August 2011, the US Food and Drug Administration granted it a fast track designation. In 2012, the results of Phase IIb clinical trials using letermovir in bone marrow transplant patients were presented at various international meetings, and the data were subsequently published in 2014.42 It`s continued clinical development is currently undertaken in agreement with Merck. Letermovir is highly potent in vitro and in vivo against cytomegalovirus. Because of a distinct mechanism of action, it does not exhibit cross-resistance with other antiviral drugs. It is predicted to be active against strains that are resistant to ganciclovir, foscarnet, and cidofovir. To date, early-phase clinical trials suggest a very low incidence of adverse effects. It targets the UL56 subunit of the viral terminase complex. Letermovir is currently in Phase III development. — NCATS

Clinical trial activity

44 trials · 49 clinical orgs · 2 marketing orgs

Phase 1
5
Phase 2
26
Phase 3
11
Phase 4
6

Earliest trial started Feb 1, 2010 (NCT01063829)

Timeline

2010s

  1. Jan 1, 2010

    Earliest Phase 2 Sponsor(trial)

  2. Dec 12, 2011

    Orphan Drug Designation

  3. Jan 1, 2014

    Merck — Earliest Phase 3 Sponsor(trial)

  4. Nov 8, 2017

    Merck — Earliest FDA Approval

  5. Nov 8, 2017

    Merck — NDA Secondary Org

  6. Nov 8, 2017

    Merck — NDA Organization

2020s

  1. Jan 1, 2023

    Earliest Phase 1 Sponsor(trial)

  2. Mar 22, 2024

    Zydus Discovery DMCC — Marketing Organization

  3. Aug 30, 2024

    Merck — Marketing Organization

Indications

Mechanism of action

Approval history

  • approvedPriority reviewFast trackBreakthroughNov 8, 2017

Chemistry & pharmacology

Loading structure…

SMILES

COc1cccc(N2CCN(C3=Nc4c(F)cccc4[C@H](CC(=O)O)N3c3cc(C(F)(F)F)ccc3OC)CC2)c1
Mol. weight
572.56 g/mol
Lipinski Ro5
2 violation(s)
Rule of 3
No
Chirality
Single Stereoisomer
Inorganic
No
Polymer
No
Delivery
Oral, Parenteral
Availability
Prescription Only

Oral

Yes

Parenteral

Yes

Topical

No

First in class

Sources

Also known as

  • aic246
  • aic246
  • letermovir
  • letermovir
  • letermovir
  • letermovir
  • mk-8228
  • mk-8228

Clinical trials

NCT IDPhaseStart dateSponsor(s)
NCT07020533Phase 1May 8, 2026City of Hope National Medical Center, National Cancer Institute (NCI)
NCT07235683Phase 4Nov 30, 2025University of Toronto
NCT07199465Phase 1Nov 19, 2025Merck
NCT07101055Phase 1Sep 30, 2025Merck, University of Queensland
NCT07079735Phase 2/Phase 3 (Phase 3)Sep 12, 2025Columbia University, Cornell University
NCT06920251Phase 2Sep 11, 2025Seoul National University
NCT07266467Phase 4May 13, 2025Anhui Medical University, Capital Medical University, Central South University, Fudan University, Guangzhou Medical University, Huazhong University of Science and Technology, Jiao Tong University, Jinlin University, Qianfo Mountain Hospital, Shandong Province, Qingdao University, Southern Medical University, Sun Yat-Sen University, Zhengzhou University
NCT06575374N/ADec 31, 2024University of Texas at Houston
NCT06812598N/ADec 16, 2024Soochow University
NCT06639854N/ANov 20, 2024University of Texas at Houston
NCT06626555Phase 2Oct 31, 2024University of London
NCT06334497Phase 3Aug 14, 2024Assistance Publique - Hôpitaux de Paris
NCT06407232Phase 3Aug 8, 2024Merck, University of Wisconsin
NCT06453460Phase 2Jun 27, 2024Chao Family Comprehensive Cancer Center, University of California, Irvine
NCT06449586N/AJun 1, 2024Jiao Tong University
NCT06341686Phase 3May 5, 2024Hospital do Rim e Hipertensão
NCT05711667Phase 3Jan 26, 2024National Cancer Institute (NCI)
NCT06066957Phase 2Jan 1, 2024Merck, University of Pennsylvania
NCT06118515Phase 1Nov 16, 2023National Institute of Allergy and Infectious Diseases (NIAID)
NCT06057194Phase 2Oct 31, 2023Hospital Universitario Reina Sofía, Universidad de Cordoba
Showing 20 of 44 trials
Page 1 / 3

Organizations

Research & Development (49)

OrganizationOrg typeTrialsAs lead sponsorPhasesEarliest year
MerckFor profit17742014
Assistance Publique - Hôpitaux de ParisAcademic/Hospital3322021
National Cancer Institute (NCI)Government3132019
APHP - Hôpital NeckerAcademic/Hospital2022021
China Academy of Chinese Medical SciencesAcademic/Hospital2212023
City of Hope National Medical CenterAcademic/Hospital2222019
Jiao Tong UniversityAcademic/Hospital2222024
National Institute of Allergy and Infectious Diseases (NIAID)Government2222021
Soochow UniversityAcademic/Hospital2222022
Tufts UniversityAcademic/Hospital2212021
University of Texas at HoustonAcademic/Hospital2212024
AiCuris Anti-infective Cures GmbHFor profit1112010
Anhui Medical UniversityAcademic/Hospital1012025
Capital Medical UniversityAcademic/Hospital1012025
Central South UniversityAcademic/Hospital1012025
Chao Family Comprehensive Cancer CenterAcademic/Hospital1012024
Columbia UniversityAcademic/Hospital1112025
Cornell UniversityAcademic/Hospital1012025
Fudan UniversityAcademic/Hospital1012025
Guangzhou Medical UniversityAcademic/Hospital1012025
49 organizations
Page 1 / 3

Marketing (4)

OrganizationOrg typeRelationshipDate
MerckFor profitNDA2Nov 8, 2017
MerckFor profitNDANov 8, 2017
MerckFor profitMKTGAug 30, 2024
Zydus Discovery DMCCFor profitMKTGMar 22, 2024