Letermovir: Treatment of human cytomegalovirus infection, antiinfective agent

Drugs of the Future

Volumn 38, Issue 5, 2013, Pages 291-298

  Verghese, Priya S ^a   Schleiss, Mark R ^a  

^a UNIVERSITY OF MINNESOTA MEDICAL SCHOOL   (United States)

Author keywords

AIC 246; Antiviral agents; Cytomegalovirus infection; Letermovir; Transplant

Indexed keywords

ARTEMISININ DERIVATIVE; BENZIMIDAVIR; CIDOFOVIR; CIDOFOVIR 3 HEXADECYLOXYPROPYL ESTER; FOSCARNET; GANCICLOVIR; GW 275175X; LEFLUNOMIDE; LETERMOVIR; PLACEBO; TACROLIMUS; TOMEGLOVIR; UNCLASSIFIED DRUG; VALGANCICLOVIR;

ANTIVIRAL ACTIVITY; ANTIVIRAL RESISTANCE; ARTICLE; CROSS RESISTANCE; CYTOMEGALOVIRUS INFECTION; DRUG BIOAVAILABILITY; DRUG DOSE ESCALATION; DRUG EFFICACY; DRUG HALF LIFE; DRUG MEGADOSE; DRUG METABOLISM; DRUG SAFETY; DRUG TOLERABILITY; EPSTEIN BARR VIRUS; GENE MUTATION; GENE PRODUCT; GRAFT SURVIVAL; HIGH RISK PATIENT; HUMAN; HUMAN CYTOMEGALOVIRUS; IMMUNOSUPPRESSIVE TREATMENT; IN VITRO STUDY; LONG TERM CARE; LYMPHOPROLIFERATIVE DISEASE; MICHAEL ADDITION; NEPHROTOXICITY; NONHUMAN; PHASE 1 CLINICAL TRIAL (TOPIC); PHASE 2 CLINICAL TRIAL (TOPIC); PHASE 3 CLINICAL TRIAL (TOPIC); POLYMERASE CHAIN REACTION; PROBABILITY; RANDOMIZED CONTROLLED TRIAL (TOPIC); SINGLE DRUG DOSE; STRUCTURE ACTIVITY RELATION; VIRUS REPLICATION;

EID: 84930537790     PISSN: 03778282     EISSN: None     Source Type: Journal    
DOI: 10.1358/dof.2013.038.05.1946425     Document Type: Article

References (55)

1. Wunberg, T., Jeske, M., Lampe, T. et al. (Bayer Health Care AG). Substituted dihydrochinazolines having antiviral properties. DE 10319612, EP 1622880, JP 2006525249, US 2005065160, US 7196086, US 2007191387, Wo 2004096778.
2. Goossen, K., Kuhn, O., Berwe, M., Krueger, J., Militzer, H.-C. (Bayer Health Care AG). Method for producing dihydroquinazolines. Cn 101863843, DE 10227517, EP 1893587, JP 2008543797, US 2009221822, US 8084604, US 2012130072, US 8372972, Wo 2006133822.
3. Boeckh, M., Geballe, A.P. Cytomegalovirus: Pathogen, paradigm, and puzzle. J Clin Invest 2011, 121(5): 1673-80.
4. Whitley, R.J. Cytomegalovirus and HIV: Inextricably entwined pathogens. Lancet 2004, 363(9427): 2101-2. (Pubitemid 38844147)
5. Webster, A., Lee, C.A., Cook D.G., Grundy, J.E., Emery, V.C., Kernoff, P.B., Griffiths, P.D: Cytomegalovirus infection and progression towards AIDS in haemophiliacs with human immunodeficiency virus infection. Lancet 1989, 2(8654) 63-6. (Pubitemid 19173297)
6. Sabin, C.A., Phillips, A.N., Lee, C.A., Janossy, G., Emery, V., Griffiths, P.D. The effect of CMV infection on progression of human immunodeficiency virus disease is a cohort of haemophilic men followed for up to 13 years from seroconversion. Epidemiol Infect 1995, 114(2): 361-72.
7. Dharnidharka, V.R., Agodoa, L.Y., Abbott, K.C. Risk factors for hospitalization for bacterial or viral infection in renal transplant recipients-An analysis of USRDS data. Am J Transplant 2007, 7(3): 653-61. (Pubitemid 46376457)
8. Dharnidharka, V.R., Stablein, D.M., Harmon, W.E. Post-transplant infections now exceed acute rejection as cause for hospitalization: A report of the NAPRTCS. Am J Transplant 2004, 4(3): 384-9. (Pubitemid 38282294)
9. Humar, A., Snydman, D. Cytomegalovirus in solid organ transplant recipients. Am J Transplant 2009, 9(Suppl. 4): S78-86.
10. Manez, R., Breinig, M.C., Linden, P. et al. Posttransplant lymphoproliferative disease in primary Epstein-Barr virus infection after liver transplantation: The role of cytomegalovirus disease. J Infect Dis 1997, 176(6): 1462-7. (Pubitemid 27518144)
11. Walker, R.C., Marshall, W.F., Strickler, J.G. et al. Pretransplantation assessment of the risk of lymphoproliferative disorder. Clin Infect Dis 1995, 20(5): 1346-53.
12. Smith, J.M., Corey, L., Bittner, R., Finn, L.S., Healey, P.J., Davis, C.L., McDonald, R.A. Subclinical viremia increases risk for chronic allograft injury in pediatric renal transplantation. J Am Soc nephrol 2010, 21(9): 1579-86.
13. Li, L., Chaudhuri, A., Weintraub, L.A. et al. Subclinical cytomegalovirus and Epstein-Barr virus viremia are associated with adverse outcomes in pediatric renal transplantation. Pediatr Transplant 2007, 11(2): 187-95. (Pubitemid 46174991)
14. Linares, L., Sanclemente, G., Cervera, C. et al. Influence of cytomegalovirus disease in outcome of solid organ transplant patients. Transplant Proc 2011, 43(6): 2145-8.
15. Razonable R.R., Humar, A.; AST Infectious Diseases Community of Practice, Cytomegalovirus in solid organ transplantation. Am J Transplant 2013, 13(Suppl. 4): 93-106.
16. Cheeran, M.C., Lokensgard, J.R., Schleiss, M.R. Neuropathogenesis of congenital cytomegalovirus infection: disease mechanisms and prospects for intervention. Clin Microbiol Rev 2009, 22(1): 99-126.
17. Boeckh, M., Ljungman, P. How we treat cytomegalovirus in hematopoietic cell transplant recipients. Blood 2009, 113(23): 5711-9.
18. Daikos, G.L., Pulido, J., Kathpalia, S.B., Jackson, G.G. Intravenous and intraocular ganciclovir for CMV retinitis in patients with AIDS or chemotherapeutic immunosuppression. Br J ophthalmol 1988, 72(7): 521-4.
19. Eid, A.J., Razonable, R.R. New developments in the management of cytomegalovirus infection after solid organ transplantation. Drugs 2010, 70(8): 965-81.
20. Strippoli, G.F., Hodson, E.M., Jones, C.J., Craig, J.C. Preemptive treatment for cytomegalovirus viremia to prevent cytomegalovirus disease in solid organ transplant recipients. Transplantation 2006, 81(2): 139-45.
21. Razonable, R.R. Cytomegalovirus infection after liver transplantation: Current concepts and challenges. World J Gastroenterol 2008, 14(31): 4849-60.
22. Kliem, V., Fricke, L., Wollbrink, T., Burg, M., Rademacher, J., Rohde, F. Improvement in long-term renal graft survival due to CMV prophylaxis with oral ganciclovir: Results of a randomized clinical trial. Am J Transplant 2008, 8(5): 975-83. (Pubitemid 351537752)
23. Lee, S.O., Razonable, R.R. Current concepts on cytomegalovirus infection after liver transplantation. World J Hepatol 2010, 2(9): 325-36.
24. Paya, C., Humar, A., Dominguez, E. et al. Efficacy and safety of valganciclovir vs. oral ganciclovir for prevention of cytomegalovirus disease in solid organ transplant recipients. Am J Transplant 2004, 4(4): 611-20. (Pubitemid 38523584)
25. Kotton, C.N., Kumar, D., Caliendo, A.M. et al. International consensus guidelines on the management of cytomegalovirus in solid organ transplantation. Transplantation 2010, 89(7): 779-95.
26. Asberg, A., Huma, A., Rollag, H. et al. Oral valganciclovir is noninferior to intravenous ganciclovir for the treatment of cytomegalovirus disease in solid organ transplant recipients. Am J Transplant 2007, 7(9): 2106-13. (Pubitemid 47247057)
27. Kimberlin, D.W., Lin, C.Y., Sánchez, P.J. et al. Effect of ganciclovir therapy on hearing in symptomatic congenital cytomegalovirus disease involving the central nervous system: A randomized, controlled trial. J Pediatr 2003, 143(1): 16-25. (Pubitemid 36928564)
28. Boivin, G., Goyette, N., Gilbert, C., Humar, A., Covington, E. Clinical impact of ganciclovir-resistant cytomegalovirus infections in solid organ transplant patients. Transpl Infect Dis 2005, 7(3-4): 166-70. (Pubitemid 43015456)
29. Limaye, A.P., Corey, L., Koelle, D.M., Davis, C.L., Boeckh, M. Emergence of ganciclovir-resistant cytomegalovirus disease among recipients of solidorgan transplants. Lancet 2000, 356(9230): 645-9. (Pubitemid 30627592)
30. Janoly-Dumenil, A., Rouvet, I., Bleyzac, N., Morfin, F., Zabot, M.T., Tod, M. A pharmacodynamic model of ganciclovir antiviral effect and toxicity for lymphoblastoid cells suggests a new dosing regimen to treat cytomegalovirus infection. Antimicrob Agents Chemother 2012, 56(7): 3732-8.
31. Griffiths, P.D., Boeckh, M. Antiviral therapy for human cytomegalovirus. In: Human Herpesviruses: Biology, Therapy, and Immunoprophylaxis. A. Arvin et al. (Eds.). Cambridge, 2007.
32. Jacobsen, T., Sifontis, N. Drug interactions and toxicities associated with the antiviral management of cytomegalovirus infection. Am J Health Syst Pharm 2010, 67(17): 1417-25.
33. Lischka, P., Zimmermann, H. Antiviral strategies to combat cytomegalovirus infections in transplant recipients. Curr opin Pharmacol 2008, 8(5): 541-8.
34. Lurain, N.S., Chou, S. Antiviral drug resistance of human cytomegalovirus. Clin Microbiol Rev 2010, 23(4): 689-712.
35. De Clercq, E. A Cutting-edge view on the current state of antiviral drug development. Med Res Rev 2013, Epub ahead of print.
36. Marty, F.M., Ljungman, P., Papanicolaou, G.A. et al. Maribavir prophylaxis for prevention of cytomegalovirus disease in recipients of allogeneic stem-cell transplants: A phase 3, double-blind, placebo-controlled, randomised trial. Lancet Infect Dis 2011, 11(4): 284-92.
37. Winston, D.J., et al., Efficacy and safety of maribavir dosed at 100 mg orally twice daily for the prevention of cytomegalovirus disease in liver transplant recipients: A randomized, double-blind, multicenter controlled trial. Am J Transplant 2012, 12(11): 3021-30.
38. Marty, F.M., Boeckh, M. Maribavir and human cytomegalovirus-what happened in the clinical trials and why might the drug have failed? Curr opin Virol 2011, 1(6): 555-62.
39. Avery, R.K., Marty, F.M., Strasfeld, L. et al. Oral maribavir for treatment of refractory or resistant cytomegalovirus infections in transplant recipients. Transplant Infect Dis 2010, 12(6): 489-96.
40. Painter, W., Robertson, A., Trost, L.C., Godkin, S., Lampert, B., Painter, G. First pharmacokinetic and safety study in humans of the novel lipid anti-viral conjugate CMX001, a broad-spectrum oral drug active against double-stranded DNA viruses. Antimicrob Agents Chemother 2012, 56(5): 2726-34.
41. Marty, F.M., Winston, D., Rowley, S.D. et al. CMX001 for prevention and control of CMV infection in CMV-seropositive allogeneic stem-cell transdose-escalation trial of safety, tolerability and antiviral activity. Biol Blood Marrow Transplant 2012, 18(2): S203-204.
42. Chou, S. Cytomegalovirus UL97 mutations in the era of ganciclovir and maribavir. Rev Med Virol 2008, 18(4): 233-46. (Pubitemid 352018847)
43. Chou, S., Waldemer, R.H., Senters, A.E., Michels, K.S., Kemble, G.W., Miner, R.C., Drew, W.L. Cytomegalovirus UL97 phosphotransferase mutations that affect susceptibility to ganciclovir. J Infect Dis 2002, 185(2): 162-9. (Pubitemid 34056439)
44. Chou, S., Wechel, L.C., Marousek, G.I. Cytomegalovirus UL97 kinase mutations that confer maribavir resistance. J Infect Dis 2007, 196(1): 91-4. (Pubitemid 46982742)
45. Chou, S., Hakki, M., Villano, S. Effects on maribavir susceptibility of cytomegalovirus UL97 kinase ATP binding region mutations detected after drug exposure in vitro and in vivo. Antivir Res 2012, 95(2): 88-92.
46. Bogner, E. Human cytomegalovirus terminase as a target for antiviral chemotherapy. Rev Med Virol 2002, 12(2): 115-27. (Pubitemid 34273046)
47. Borst, E.M., Kleine-Albers, J., Gavaev, I. et al. The human cytomegalovirus UL51 protein is sssential for viral genome cleavage-packaging and interacts with the terminase subunits pUL56 and pUL89. J Virol 2013, 87(3): 1720-32.
48. Schleiss, M.R., McVoy, M.A. Overview of congenitally and perinatally acquired cytomegalovirus infections: Recent advances in antiviral therapy. Expert Rev Anti Infect Ther 2004, 2(3): 389-403. (Pubitemid 38745098)
49. Schleiss, M.R., Bernstein, D.I., McVoy, M.A. et al. The non-nucleoside antiviral, BAY 38-4766, protects against cytomegalovirus (CMV) disease and mortality in immunocompromised guinea pigs. Antiviral Res 2005, 65(1): 35-43. (Pubitemid 40094772)
50. Lischka, P., Hewlett, G., Wunberg, T. et al. In vitro and in vivo activities of the novel anticytomegalovirus compound AIC246. Antimicrob Agents Chemother 2010, 54(3): 1290-7.
51. Marschall, M., Stamminger, T., Urban, A. et al. In vitro evaluation of the activities of the novel anticytomegalovirus compound AIC246 (letermovir) against herpesviruses and other human pathogenic viruses. Antimicrob Agents Chemother 2012, 56(2): 1135-7.
52. Goldner, T., Hewlett, G., Ettischer, N., Ruebsamen-Schaeff, H., Zimmermann, H., Lischka, P. The novel anticytomegalovirus compound AIC246 (letermovir) inhibits human cytomegalovirus replication through a specific antiviral mechanism that involves the viral terminase. J Virol 2011, 85(20): 10884-93.
53. Kaul, D.R., Stoelben, S., Cober, E., et al. First report of successful treatment of multidrug-resistant cytomegalovirus disease with the novel anti-CMV compound AIC246. Am J Transplant 2011, 11(5): 1079-84.
54. Lea, A.P., Bryson, H.M. Cidofovir. Drugs 1996, 52(2): 225-30; discussion 231. (Pubitemid 26259619)
55. Lalezari, J.P., Aberg, J.A., Wang, L.H. et al. Phase I dose escalation trial evaluating the pharmacokinetics, anti-human cytomegalovirus (HCMV) activity, and safety of 1263W94 in human immunodeficiency virus-infected men with asymptomatic HCMV shedding. Antimicrob Agents Chemother 2002, 46(9): 2969-76.