letermovir
Trade name: prevymis
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
Earliest trial started Feb 1, 2010 (NCT01063829)
Timeline
2010s
2020s
- Jan 1, 2023
Earliest Phase 1 Sponsor(trial)
- Mar 22, 2024
Zydus Discovery DMCC — Marketing Organization
- Aug 30, 2024
Merck — Marketing Organization
Indications
Approved for
Studied for
- Cytomegalovirus · Phase 4
- Drug-Related Side Effects and Adverse Reactions · Phase 4
- Graft vs Host Disease · Phase 2
- Heart Failure · Phase 2/Phase 3
- Heart Transplantation · Phase 4
- Hematopoietic Stem Cell Transplantation · Phase 2
- HIV · Phase 2
- HIV Infections · Phase 2
- Hodgkin Disease · Phase 2
- Kidney Failure, Chronic · Phase 1
- Kidney Transplantation · Phase 3
- Leukemia, Lymphocytic, Chronic, B-Cell · Phase 2
- Leukemia, Myelogenous, Chronic, BCR-ABL Positive · Phase 2
- Leukemia, Myeloid · Phase 1
- Leukemia, Myeloid, Acute · Phase 2
- Leukemia, Prolymphocytic, B-Cell · Phase 2
- Leukemia, Prolymphocytic, T-Cell · Phase 2
- Lung Transplantation · Phase 4
- Lymphoma · Phase 3
- Lymphoma, Non-Hodgkin · Phase 2
- Lymphoma, T-Cell, Peripheral · Phase 2
- Multiple Myeloma · Phase 2
- Myelodysplastic Syndromes · Phase 2
- Myeloproliferative Disorders · Phase 2
- Neoplasms · Phase 3
- Neutropenia · Phase 4
- Organ Transplantation · Phase 4
- Pancreas Transplantation · Phase 3
- Precursor Cell Lymphoblastic Leukemia-Lymphoma · Phase 2
- Pregnant People · Phase 3
- Primary Myelofibrosis · Phase 2
- Sezary Syndrome · Phase 2
- Transplants · Phase 4
Mechanism of action
Approval history
- approvedPriority reviewFast trackBreakthroughNov 8, 2017
Chemistry & pharmacology
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
Sources
- ChEMBLCHEMBL1241951 ↗
- WikipediaLetermovir ↗
- NCATS1H09Y5WO1F ↗
Also known as
- aic246
- aic246
- letermovir
- letermovir
- letermovir
- letermovir
- mk-8228
- mk-8228
Clinical trials
| NCT ID | Phase | Start date | Sponsor(s) |
|---|---|---|---|
| NCT07020533 | Phase 1 | May 8, 2026 | City of Hope National Medical Center, National Cancer Institute (NCI) |
| NCT07235683 | Phase 4 | Nov 30, 2025 | University of Toronto |
| NCT07199465 | Phase 1 | Nov 19, 2025 | Merck |
| NCT07101055 | Phase 1 | Sep 30, 2025 | Merck, University of Queensland |
| NCT07079735 | Phase 2/Phase 3 (Phase 3) | Sep 12, 2025 | Columbia University, Cornell University |
| NCT06920251 | Phase 2 | Sep 11, 2025 | Seoul National University |
| NCT07266467 | Phase 4 | May 13, 2025 | Anhui 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 |
| NCT06575374 | N/A | Dec 31, 2024 | University of Texas at Houston |
| NCT06812598 | N/A | Dec 16, 2024 | Soochow University |
| NCT06639854 | N/A | Nov 20, 2024 | University of Texas at Houston |
| NCT06626555 | Phase 2 | Oct 31, 2024 | University of London |
| NCT06334497 | Phase 3 | Aug 14, 2024 | Assistance Publique - Hôpitaux de Paris |
| NCT06407232 | Phase 3 | Aug 8, 2024 | Merck, University of Wisconsin |
| NCT06453460 | Phase 2 | Jun 27, 2024 | Chao Family Comprehensive Cancer Center, University of California, Irvine |
| NCT06449586 | N/A | Jun 1, 2024 | Jiao Tong University |
| NCT06341686 | Phase 3 | May 5, 2024 | Hospital do Rim e Hipertensão |
| NCT05711667 | Phase 3 | Jan 26, 2024 | National Cancer Institute (NCI) |
| NCT06066957 | Phase 2 | Jan 1, 2024 | Merck, University of Pennsylvania |
| NCT06118515 | Phase 1 | Nov 16, 2023 | National Institute of Allergy and Infectious Diseases (NIAID) |
| NCT06057194 | Phase 2 | Oct 31, 2023 | Hospital Universitario Reina Sofía, Universidad de Cordoba |
Organizations
Research & Development (49)
Marketing (4)
| Organization | Org type | Relationship | Date |
|---|---|---|---|
| Merck | For profit | NDA2 | Nov 8, 2017 |
| Merck | For profit | NDA | Nov 8, 2017 |
| Merck | For profit | MKTG | Aug 30, 2024 |
| Zydus Discovery DMCC | For profit | MKTG | Mar 22, 2024 |