Letermovir (AIC246) - A novel drug under development for prevention and treatment of cytomegalovirus infections acting via a novel mechanism of action

European Infectious Disease

Volumn 5, Issue 2, 2011, Pages 112-114

  Zimmermann, Holger ^a   Lischka, Peter ^a   Helga, Rübsamen Schaeff ^a  

^a AiCuris GmbH   (Germany)

Author keywords

AIC246; Antiviral therapy; Cytomegalovirus; Letermovir

Indexed keywords

EID: 84857563335     PISSN: 17551137     EISSN: 17551145     Source Type: Journal    
DOI: None     Document Type: Article

References (26)

1. Hahn G, Jores R, Mocarski ES, Cytomegalovirus remains latent in a common precursor of dendritic and myeloid cells, Proc Natl Acad Sci U S A, 1998;95(7):3937-42.
2. Stevens JG, Human herpesviruses: a consideration of the latent state, Microbiol Rev, 1989;53(3):318-32.
3. Eid AJ, Razonable RR, New developments in the management of cytomegalovirus infection after solid organ transplantation, Drugs, 2010;70(8):965-81.
4. Ljungman P, Hakki M, Boeckh M, Cytomegalovirus in hematopoietic stem cell transplant recipients, Hematol Oncol Clin North Am, 2011;25(1):151-69.
5. Boppana SB, Fowler KB, Pass RF, et al., Congenital cytomegalovirus infection: association between virus burden in infancy and hearing loss, J Pediatr, 2005;146(6):817-23.
6. Grosse SD, Ross DS, Dollard SC, Congenital cytomegalovirus (CMV) infection as a cause of permanent bilateral hearing loss: a quantitative assessment, J Clin Virol, 2008;41(2):57-62.
7. Arvin AM, Fast P, Myers M, et al., Vaccine development to prevent cytomegalovirus disease: Report from the national vaccine advisory committee, Clin Infect Dis, 2004;39:233-9.
8. Hunt PW, Martin JN, Sinclair E, et al., Valganciclovir reduces T cell activation in HIV-infected individuals with incomplete CD4+ T cell recovery on antiretroviral therapy, J Infect Dis, 2011;203(10):1474-83.
9. Wiltshire H, Hirankarn S, Farrell C, et al., Pharmacokinetic profile of ganciclovir after its oral administration and from its prodrug, valganciclovir, in solid organ transplant recipients, Clin Pharmacokinet, 2005;44:495-507.
10. Wiltshire H, Paya CV, Pescovitz MD, et al., Pharmacodynamics of oral ganciclovir and valganciclovir in solid organ transplant recipients, Transplantation, 2005;79:1477-83.
11. Steininger C, Novel therapies for cytomegalovirus disease, Recent Patents Anti-Infect Drug Disc, 2007;2:53-72.
12. De Clercq E, Holy A, Acyclic nucleoside phosphonates: a key class of antiviral drugs, Nat Rev Drug Discov, 2005;4:928-40.
13. Jacobson MA, Treatment of cytomegalovirus retinitis in patients with the acquired immunodeficiency syndrome, N Engl J Med, 1997;337:105-14.
14. Mercorelli B, Sinigalia E, Loregian A, Palu G, Human cytomegalovirus DNA replication: antiviral targets and drugs, Rev Med Virol, 2008;18:177-210.
15. Wagstaff AJ, Bryson HM, Foscarnet, A reappraisal of its antiviral activity, pharmacokinetic properties and therapeutic use in immunocompromised patients with viral infections, Drugs, 1994;48:199-226.
16. Limaye AP, Corey L, Koelle DM, et al., Emergence of ganciclovir-resistant cytomegalovirus disease among recipients of solid-organ transplants, Lancet, 2000;356:645-9.
17. Eckle T, Lang P, Prix L, et al., Rapid development of ganciclovir-resistant cytomegalovirus infection in children after allogeneic stem cell transplantation in the early phase of immune cell recovery, Bone Marrow Transplant, 2002;30:433-9.
18. Gilbert C, Boivin G, Human cytomegalovirus resistance to antiviral drugs, Antimicrob Agents Chemother, 2005;49:873-83.
19. Scott GM, Weinberg A, Rawlinson WD, Chou S, Multidrug resistance conferred by novel DNA polymerase mutations in human cytomegalovirus isolates, Antimicrob Agents Chemother, 2007;51:89-94.
20. Reefschlaeger J, Bender W, Hallenberger S, et al., Novel non-nucleoside inhibitors of cytomegaloviruses (BAY 38-4766): in vitro and in vivo antiviral activity and mechanism of action, J Antimicrob Chemother, 2001;48(6):757-67.
21. Buerger I, Reefschlaeger J, Bender W, et al., A novel nonnucleoside inhibitor specifically targets cytomegalovirus DNA maturation via the UL89 and UL56 gene products, J Virol, 2001;75(19):9077-86.
22. 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.
23. Goldner T, Hewlett G, Ettischer N, et al., The novel anti-cytomegalovirus compound AIC246 inhibits HCMV replication through a specific antiviral mechanism that involves the viral terminase, J Virol, 2011;(Epub ahead of print).
24. Kropeit D, McCormick D, VonRichter O, et al., Phase I safety and PK data of the novel anti-HCMV terminase inhibitor AIC246, Abstract 1994, Presented at: the 50th Interscience Conference Antimicrobial Agents Chemother (ICAAC), Boston, MA, 12-15 September 2010.
25. Zimmermann H, Stoelben S, Renders L, et al., A novel non-nucleoside compound with activity against human cytomegalovirus - overview of clinical trials and resistance breaking activity, Abstract V1256b, Presented at: the 49th Interscience Conference Antimicrobial Agents Chemother (ICAAC), San Francisco, CA, 12-15 September 2009.
26. Kaul DR, 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;11:1079-84.