Future Classes of Hepatitis C Virus Therapeutic Agents

Infectious Disease Clinics of North America

Volumn 26, Issue 4, 2012, Pages 949-966

  Chen, Jennifer Y ^a   Chung, Raymond T ^a  

^a MASSACHUSETTS GENERAL HOSPITAL   (United States)

Author keywords

Antiviral therapeutics; Direct acting antivirals; Hepatitis C virus; Host targeted agents

Indexed keywords

ABT 072; ABT 450; ACH 1625; ASUNAPREVIR; BI 207127; BOCEPREVIR; DACLATASVIR; DANOPREVIR; FALDAPREVIR; FILIBUVIR; GS 9256; GS 9451; IDX 184; IDX 375; LOMIBUVIR; MERICITABINE; MK 5172; NARLAPREVIR; NUCLEOSIDE ANALOG; PEGINTERFERON; PROTEINASE INHIBITOR; RIBAVIRIN; RITONAVIR; SETROBUVIR; SIMEPREVIR; SOFOSBUVIR; TEGOBUVIR; TELAPREVIR; UNCLASSIFIED DRUG; UNINDEXED DRUG; VANIPREVIR;

ANEMIA; ANTIVIRAL ACTIVITY; DIARRHEA; DRUG APPROVAL; DRUG EFFICACY; DRUG ERUPTION; DRUG HALF LIFE; DRUG INDUCED HEADACHE; DRUG MECHANISM; DRUG TOLERABILITY; DYSGEUSIA; FATIGUE; GENETIC VARIABILITY; HEPATITIS; HEPATITIS C; HUMAN; HYPERBILIRUBINEMIA; IN VITRO STUDY; JAUNDICE; LIFE CYCLE; MYALGIA; NAUSEA; NEUTROPENIA; PHASE 2 CLINICAL TRIAL (TOPIC); PRURITUS; REVIEW; SIDE EFFECT; VIROLOGY; VOMITING;

EID: 84867675042     PISSN: 08915520     EISSN: 15579824     Source Type: Journal    
DOI: 10.1016/j.idc.2012.08.003     Document Type: Review

References (86)

1. Hatzakis A., Wait S., Bruix J., et al. The state of hepatitis B and C in Europe: report from the hepatitis B and C summit conference. J Viral Hepat 2011, 18(Suppl 1):1-16.
2. Page K., Hahn J.A., Evans J., et al. Acute hepatitis C virus infection in young adult injection drug users: a prospective study of incident infection, resolution, and reinfection. J Infect Dis 2009, 200(8):1216-1226.
3. Wang C.C., Krantz E., Klarquist J., et al. Acute hepatitis C in a contemporary US cohort: modes of acquisition and factors influencing viral clearance. J Infect Dis 2007, 196(10):1474-1482.
4. Poynard T., McHutchison J., Manns M., et al. Impact of pegylated interferon alfa-2b and ribavirin on liver fibrosis in patients with chronic hepatitis C. Gastroenterology 2002, 122(5):1303-1313.
5. Morgan T.R., Ghany M.G., Kim H.Y., et al. Outcome of sustained virological responders with histologically advanced chronic hepatitis C. Hepatology 2010, 52(3):833-844.
6. Manns M.P., McHutchison J.G., Gordon S.C., et al. Peginterferon alfa-2b plus ribavirin compared with interferon alfa-2b plus ribavirin for initial treatment of chronic hepatitis C: a randomised trial. Lancet 2001, 358(9286):958-965.
7. Fried M.W., Shiffman M.L., Reddy K.R., et al. Peginterferon alfa-2a plus ribavirin for chronic hepatitis C virus infection. N Engl J Med 2002, 347(13):975-982.
8. Hadziyannis S.J., Sette H., Morgan T.R., et al. Peginterferon-alpha2a and ribavirin combination therapy in chronic hepatitis C: a randomized study of treatment duration and ribavirin dose. Ann Intern Med 2004, 140(5):346-355.
9. Veldt B.J., Heathcote E.J., Wedemeyer H., et al. Sustained virologic response and clinical outcomes in patients with chronic hepatitis C and advanced fibrosis. Ann Intern Med 2007, 147(10):677-684.
10. Swain M.G., Lai M.Y., Shiffman M.L., et al. A sustained virologic response is durable in patients with chronic hepatitis C treated with peginterferon alfa-2a and ribavirin. Gastroenterology 2010, 139(5):1593-1601.
11. Kagawa T., Keeffe E.B. Long-term effects of antiviral therapy in patients with chronic hepatitis C. Hepat Res Treat 2010, 2010:562578.
12. Wakita T., Pietschmann T., Kato T., et al. Production of infectious hepatitis C virus in tissue culture from a cloned viral genome. Nat Med 2005, 11(7):791-796.
13. Lindenbach B.D., Meuleman P., Ploss A., et al. Cell culture-grown hepatitis C virus is infectious in vivo and can be recultured in vitro. Proc Natl Acad Sci U S A 2006, 103(10):3805-3809.
14. Dubuisson J., Helle F., Cocquerel L. Early steps of the hepatitis C virus life cycle. Cell Microbiol 2008, 10(4):821-827.
15. Pawlotsky J.M. Hepatitis C virus genetic variability: pathogenic and clinical implications. Clin Liver Dis 2003, 7(1):45-66.
16. McHutchison J.G., Everson G.T., Gordon S.C., et al. Telaprevir with peginterferon and ribavirin for chronic HCV genotype 1 infection. N Engl J Med 2009, 360(18):1827-1838.
17. McHutchison J.G., Manns M.P., Muir A.J., et al. Telaprevir for previously treated chronic HCV infection. N Engl J Med 2010, 362(14):1292-1303.
18. Jacobson I.M., McHutchison J.G., Dusheiko G., et al. Telaprevir for previously untreated chronic hepatitis C virus infection. N Engl J Med 2011, 364(25):2405-2416.
19. Poordad F., McCone J., Bacon B.R., et al. Boceprevir for untreated chronic HCV genotype 1 infection. N Engl J Med 2011, 364(13):1195-1206.
20. Bacon B.R., Gordon S.C., Lawitz E., et al. Boceprevir for previously treated chronic HCV genotype 1 infection. N Engl J Med 2011, 364(13):1207-1217.
21. Rong L., Dahari H., Ribeiro R.M., et al. Rapid emergence of protease inhibitor resistance in hepatitis C virus. Sci Transl Med 2010, 2(30):30ra32.
22. Sarrazin C., Kieffer T.L., Bartels D., et al. Dynamic hepatitis C virus genotypic and phenotypic changes in patients treated with the protease inhibitor telaprevir. Gastroenterology 2007, 132(5):1767-1777.
23. Susser S., Welsch C., Wang Y., et al. Characterization of resistance to the protease inhibitor boceprevir in hepatitis C virus-infected patients. Hepatology 2009, 50(6):1709-1718.
24. Ciesek S., von Hahn T., Manns M.P. Second-wave protease inhibitors: choosing an heir. Clin Liver Dis 2011, 15(3):597-609.
25. Halfon P., Locarnini S. Hepatitis C virus resistance to protease inhibitors. J Hepatol 2011, 55(1):192-206.
26. Sulkowski MS, Ferenci P, Emanoil C, et al. SILEN-C1: Early antiviral activity and safety of BI 201335 combined with peginterferon alfa-2a and ribavirin in treatment-naive patients with chronic genotype 1 HCV infection. Presented at the 60th Annual Meeting of the American Association for the Study of Liver Diseases. Boston, (MA), October 30-November 3, 2009.
27. Sulkowski MS, Bourliere M, Bronowicki JP, et al. SILEN-C2: sustained virologic response (SVR) and safety of BI201335 combined with peginterferon alfa-2a and ribavirin (P/R) in chronic HCV genotype-1 patients with non-response to P/R. Presented at the 46th Annual Meeting of the European Association for the Study of the Liver. Berlin (Germany), March 30-April 3, 2011.
28. Zeuzem S., Andreone P., Pol S., et al. Telaprevir for retreatment of HCV infection. N Engl J Med 2011, 364(25):2417-2428.
29. Zeuzem S, Soriano V, Asselah T, et al. SVR4 and SVR12 with an interferon-free regimen of BI 201335 and BI 207127, +/- ribavirin, in treatment-naive patients with chronic genotype-1 HCV infection: interim results of SOUND-C2. Presented at the 47th Annual Meeting of the European Association for the Study of the Liver. Barcelona (Spain), April 18-22, 2012.
30. Lin T.I., Lenz O., Fanning G., et al. In vitro activity and preclinical profile of tmc435350, a potent hepatitis C virus protease inhibitor. Antimicrob Agents Chemother 2009, 53(4):1377-1385.
31. Fried M, Buti M, Dore GJ, et al. Efficacy and safety of TMC435 in combination with peginterferon α-2a and ribavirin in treatment-naive genotype-1 HCV patients: 24-week interim results from the pillar study. Presented at the 61st Annual Meeting of the American Association for the Study of Liver Diseases. Boston (MA), October 29-November 2, 2010.
32. Fried M, Buti M, Dore GJ, et al. TMC435 in combination with peginterferon and ribavirin in treatment-naive HCV genotype 1 patients: Final analysis of the pillar phase IIb study. Presented at the 62nd Annual Meeting of the American Association for the Study of Liver Diseases. San Francisco (CA), November 4-8, 2011.
33. Lenz O., Verbinnen T., Lin T.I., et al. In vitro resistance profile of the hepatitis C virus ns3/4a protease inhibitor tmc435. Antimicrob Agents Chemother 2010, 54(5):1878-1887.
34. Forestier N., Larrey D., Guyader D., et al. Treatment of chronic hepatitis C patients with the ns3/4a protease inhibitor danoprevir (itmn-191/rg7227) leads to robust reductions in viral RNA: a phase 1b multiple ascending dose study. J Hepatol 2011, 54(6):1130-1136.
35. Terrault N, Cooper C, Balar LA, et al. High sustained virologic response (SVR24) rates with response-guided danoprevir (DNV; RG7227) plus PegIFN α-2a (40KD) and ribavirin (P/R) in treatment-naive HCV genotype 1 (G1) patients: results from the ATLAS study. Presented at the 62nd Annual Meeting of the American Association for the Study of Liver Diseases. San Francisco (CA), November 4-8, 2011.
36. Gane E.J., Rouzier R., Stedman C., et al. Antiviral activity, safety, and pharmacokinetics of danoprevir/ritonavir plus peg-IFN alpha-2a/RBV in hepatitis C patients. J Hepatol 2011, 55(5):972-979.
37. Graham D, Acosta A, Guo Z, et al. MK-5172, a second generation HCV NS3/4A protease inhibitor is active against common resistance associated variants (RAVs) and exhibits cross-genotype activity. Presented at the 62nd Annual Meeting of the American Association for the Study of Liver Diseases. San Francisco (CA), November 5-8, 2011.
38. Petry AS, Fraser IP, Van Dyck K, et al. Safety and antiviral activity of MK-5172, a next-generation HCV NS3/4a protease inhibitor with a broad HCV genotypic activity spectrum and potent activity against known resistance mutants, in genotype 1 and 3 HCV-infected patients. Presented at the 62nd Annual Meeting of the American Association for the Study of Liver Diseases. San Francisco (CA), November 5-8, 2011.
39. Kukolj G., McGibbon G.A., McKercher G., et al. Binding site characterization and resistance to a class of non-nucleoside inhibitors of the hepatitis C virus ns5b polymerase. J Biol Chem 2005, 280(47):39260-39267.
40. Lawitz E, Lalezari JP, Hassanein T, et al. Once-daily PSI-7977 plus Peg/RBV in treatment-naïve patients with HCV GT1: robust end of treatment response rates are sustained post-treatment. Presented at the 62nd Annual Meeting of the American Association for the Study of Liver Diseases (AASLD 2011). San Francisco, November 4-8. 2011.
41. Gane EJ, Stedman CA, Hyland RH, et al. ELECTRON: once daily PSI-7977 plus RBV in HCV GT1/2/3. Presented at the 47th Annual Meeting of the European Association for the Study of the Liver (EASL). Barcelona (Spain), April 18-22, 2012.
42. EASL 2012: Gilead announces early sustained virologic response rates for GS-7977 plus ribavirin in genotype 1 treatment-naïve hepatitis C patients. 2012. Available at: Accessed May 5, 2012. http://hepatitiscresearchandnewsupdates.blogspot.com/2012/04/easl-2012-gilead-announces-early.html%23.T7v6_FIZd8E.
43. Gane EJ, Stedman CA, Hyland RH, et al. PSI-7977: ELECTRON interferon is not required for sustained virologic response in treatment-naïve patients with HCV GT2 or GT3. Presented at the 62nd Annual Meeting of the American Association for the Study of Liver Diseases. San Francisco (CA), November 5-8, 2011.
44. Le Pogam S., Seshaadri A., Ewing A., et al. Rg7128 alone or in combination with pegylated interferon-alpha2a and ribavirin prevents hepatitis C virus (HCV) replication and selection of resistant variants in HCV-infected patients. J Infect Dis 2010, 202(10):1510-1519.
45. Pockros P, Jensen D, Tsai N, et al. First SVR data with the nucleoside analogue polymerase inhibitor mericitabine (RG7128) combined with peginterferon/ribavirin in treatment-naive HCV G1/4 patients: interim analysis from the JUMP-C trial. Presented at the 46th Annual Meeting of the European Association for the Study of the Liver. Berlin (Germany), March 30-April 3, 2011.
46. Lawitz E, Jacobson I, Godofsky E, et al. A phase 2b trial comparing 24 to 48 weeks treatment with tegobuvir (GS-9190)/PEG/RBV to 48 weeks treatment with PEG/RBV for chronic genotype 1 HCV infection. Presented at the European Association for the Study of the Liver (EASL) 46th Annual Meeting. Berlin (Germany), March 30-April 3, 2011.
47. Di Bisceglie AM, Nelson DR, Gane E, et al. VX-222 with TVR alone or in combination with peginterferon alfa-2a and ribavirin in treatment-naive patients with chronic hepatitis C: ZENITH study interim results. Presented at the 46th Annual Meeting of the European Association for the Study of the Liver. Berlin (Germany), March 30-April 3, 2011.
48. Fridell R.A., Qiu D., Valera L., et al. Distinct functions of ns5a in hepatitis C virus RNA replication uncovered by studies with the ns5a inhibitor BMS-790052. J Virol 2011, 85(14):7312-7320.
49. Ferraris P., Blanchard E., Roingeard P. Ultrastructural and biochemical analyses of hepatitis C virus-associated host cell membranes. J Gen Virol 2010, 91(Pt 9):2230-2237.
50. Macdonald A., Harris M. Hepatitis C virus ns5a: tales of a promiscuous protein. J Gen Virol 2004, 85(Pt 9):2485-2502.
51. Lan K.H., Lan K.L., Lee W.P., et al. HCV ns5a inhibits interferon-alpha signaling through suppression of stat1 phosphorylation in hepatocyte-derived cell lines. J Hepatol 2007, 46(5):759-767.
52. Gish R.G., Meanwell N.A. The ns5a replication complex inhibitors: difference makers?. Clin Liver Dis 2011, 15(3):627-639.
53. Pol S, Ghalib RH, Rustgi VK, et al. First report of SVR12 for a NS5A replication complex inhibitor, BMS-790052, in combination with PegIFNα-2a and RBV: phase IIA trial in treatment-naive HCV genotype 1 subjects. Presented at the 46th Annual Meeting of the European Association for the Study of the Liver (EASL). Berlin, March 30-April 3, 2011.
54. Sulkowski M, Gardiner D, Lawitz E, et al. Potent viral suppression with all-oral combination of daclatasvir (NS5A inhibitor) and GS-7977 (NS5B inhibitor), +/- ribavirin, in treatment-naive patients with chronic HCV GT1, 2, or 3. Presented at the 47th Annual Meeting of the European Association for the Study of the Liver. Barcelona (Spain), April 18-22, 2012.
55. Suzuki F, Ikeda K, Toyota J, et al. Dual oral therapy with the NS5a inhibitor daclatasvir (BMS-790052) and NS3 protease inhibitor asunaprevir BMS-650032) in HCV genotype 1b-infected null responders or ineligible/intolerant to peginterferon/ribavirin. Presented at the 47th Annual Meeting of the European Association for the Study of the Liver. Barcelona (Spain), April 18-22, 2012.
56. Ge D., Fellay J., Thompson A.J., et al. Genetic variation in IL28B predicts hepatitis C treatment-induced viral clearance. Nature 2009, 461:399-401.
57. Thompson A.J., Muir A.J., Sulkowski M.S., et al. Interleukin-28B polymorphism improves viral kinetics and is the strongest pretreatment predictor of sustained virologic response in genotype 1 hepatitis C virus. Gastroenterology 2010, 139:120-129.
58. Chu T.W., Kulkarni R., Gane E.J., et al. Effect of IL28B genotype on early viral kinetics during interferon-free treatment of patients with chronic hepatitis C. Gastroenterology 2012, 142:790-795.
59. Kotenko S.V., Gallagher G., Baurin V.V., et al. IFN-lambdas mediate antiviral protection through a distinct class II cytokine receptor complex. Nat Immunol 2003, 4(1):69-77.
60. Sheppard P., Kindsvogel W., Xu W., et al. Il-28, IL-29 and their class II cytokine receptor IL-28R. Nat Immunol 2003, 4(1):63-68.
61. Gad H.H., Dellgren C., Hamming O.J., et al. Interferon-lambda is functionally an interferon but structurally related to the interleukin-10 family. J Biol Chem 2009, 284(31):20869-20875.
62. Zhang L., Jilg N., Shao R.X., et al. IL28b inhibits hepatitis C virus replication through the jak-stat pathway. J Hepatol 2011, 55(2):289-298.
63. Doyle S.E., Schreckhise H., Khuu-Duong K., et al. Interleukin-29 uses a type 1 interferon-like program to promote antiviral responses in human hepatocytes. Hepatology 2006, 44(4):896-906.
64. Sommereyns C., Paul S., Staeheli P., et al. IFN-lambda (IFN-lambda) is expressed in a tissue-dependent fashion and primarily acts on epithelial cells in vivo. PLoS Pathog 2008, 4(3):e1000017.
65. Muir A.J., Shiffman M.L., Zaman A., et al. Phase 1b study of pegylated interferon lambda 1 with or without ribavirin in patients with chronic genotype 1 hepatitis C virus infection. Hepatology 2010, 52(3):822-832.
66. Zeuzem S, Arora S, Bacon B, et al. Pegylated interferon-lambda (PegIFN-λ) shows superior viral response with improved safety and tolerability versus PegIFNα-2a in HCV patients (G1/2/3/4): EMERGE phase IIb through week 12. Presented at the 46th Annual Meeting of the European Association for the Study of the Liver. Berlin (Germany), March 30-April 3, 2011.
67. Coelmont L., Hanoulle X., Chatterji U., et al. Deb025 (alisporivir) inhibits hepatitis C virus replication by preventing a cyclophilin A induced cis-trans isomerisation in domain II of ns5a. PLoS One 2010, 5(10):e13687.
68. Hanoulle X., Badillo A., Wieruszeski J.M., et al. Hepatitis C virus ns5a protein is a substrate for the peptidyl-prolyl cis/trans isomerase activity of cyclophilins A and B. J Biol Chem 2009, 284(20):13589-13601.
69. Teraoka S., Mishiro S., Ebihara K., et al. Effect of cyclosporine on proliferation of non-A, non-B hepatitis virus. Transplant Proc 1988, 20(3 Suppl 3):868-876.
70. Landrieu I., Hanoulle X., Bonachera F., et al. Structural basis for the non-immunosuppressive character of the cyclosporin A analogue debio 025. Biochemistry 2010, 49(22):4679-4686.
71. Crabbe R., Vuagniaux G., Dumont J.M., et al. An evaluation of the cyclophilin inhibitor debio 025 and its potential as a treatment for chronic hepatitis C. Expert Opin Investig Drugs 2009, 18(2):211-220.
72. Flisiak R., Feinman S.V., Jablkowski M. The cyclophilin inhibitor debio 025 combined with peg ifnalpha2a significantly reduces viral load in treatment-naive hepatitis C patients. Hepatology 2009, 49(5):1460-1468.
73. Flisiak R, Pawlotsky JM, Crabbé R, et al. Once daily alisporivir (DEB025) plus pegIFNalfa2a/ribavirin results in superior sustained virologic response (SVR24) in chronic hepatitis C genotype 1 treatment naive patients. Presented at the 46th Annual Meeting of the European Association for the Study of the Liver. Berlin (Germany), March 30-April 3, 2011.
74. Pawlotsky JM, Sarin SK, Foster G, et al. Alisporivir plus ribavirin is highly effective as interferon-free or interferon-add-on regimen in previously untreated HCV-GT2 or GT3 patients: SVR12 results from VITAL-1 phase 2b study. Presented at the 47th Annual Meeting of the European Association for the Study of the Liver. Barcelona (Spain), April 18-22, 2012.
75. Guo H., Ingolia N.T., Weissman J.S., et al. Mammalian micrornas predominantly act to decrease target mRNA levels. Nature 2010, 466(7308):835-840.
76. Bartel D.P. MicroRNAs: target recognition and regulatory functions. Cell 2009, 136(2):215-233.
77. Jopling C.L., Yi M., Lancaster A.M., et al. Modulation of hepatitis C virus RNA abundance by a liver-specific microrna. Science 2005, 309(5740):1577-1581.
78. Jopling C.L., Schutz S., Sarnow P. Position-dependent function for a tandem microrna mir-122-binding site located in the hepatitis C virus RNA genome. Cell Host Microbe 2008, 4(1):77-85.
79. Jangra R.K., Yi M., Lemon S.M. Regulation of hepatitis C virus translation and infectious virus production by the microrna mir-122. J Virol 2010, 84(13):6615-6625.
80. Reesink HW, Janssen HL, Zeuzem S, et al. Final results: randomized, double-blind, placebo-controlled safety, anti-viral proof-of-concept study of miravirsen, an oligonucleotide targeting miR-122, in treatment-naive patients with genotype 1 chronic HCV infection. Presented at the 47th Annual Meeting of the European Association for the Study of the Liver. Barcelona (Spain), April 18-22, 2012.
81. Herker E., Ott M. Unique ties between hepatitis C virus replication and intracellular lipids. Trends Endocrinol Metab 2011, 22(6):241-248.
82. Ye J., Wang C., Sumpter R., et al. Disruption of hepatitis C virus RNA replication through inhibition of host protein geranylgeranylation. Proc Natl Acad Sci U S A 2003, 100(26):15865-15870.
83. Peng L.F., Schaefer E.A., Maloof N., et al. Ceestatin, a novel small molecule inhibitor of hepatitis C virus replication, inhibits 3-hydroxy-3-methylglutaryl-coenzyme A synthase. J Infect Dis 2011, 204(4):609-616.
84. Ikeda M., Abe K., Yamada M., et al. Different anti-hcv profiles of statins and their potential for combination therapy with interferon. Hepatology 2006, 44(1):117-125.
85. O'Leary J.G., Chan J.L., McMahon C.M., et al. Atorvastatin does not exhibit antiviral activity against HCV at conventional doses: a pilot clinical trial. Hepatology 2007, 45(4):895-898.
86. Georgescu EF, Streba L, Teodorescu R, et al. Potential enhancement of both early (EVR) and sustained (SVR) virological response by fluvastatin in chronic hepatitis C treated with standard pegIFN-ribavirin therapy. A pilot study. Presented at the European Association for the Study of the Liver, International Liver Conference, Berlin (Germany), March 30-April 3, 2011.