What are the promising new therapies in the field of chronic hepatitis C after the first-generation direct-acting antivirals?

Current Gastroenterology Reports

Volumn 15, Issue 1, 2013, Pages

  Hunt, Douglas ^a   Pockros, Paul ^a,b,c  

^a SCRIPPS CLINIC   (United States)

^b SCRIPPS TRANSLATIONAL SCIENCE INSTITUTE   (United States)

^c SCRIPPS RESEARCH INSTITUTE   (United States)

Author keywords

Chronic hepatitis C; First generation direct acting antivirals; New therapies

Indexed keywords

ABT 072; ABT 333; ABT 450; ANTIVIRUS AGENT; ASUNAPREVIR; BALAPIRAVIR; BI 207127; CYCLOPHILIN B; DACLATASVIR; DANOPREVIR; ENZYME INHIBITOR; FALDAPREVIR; FILIBUVIR; GS 9256; LOMIBUVIR; MERICITABINE; NONNUCLEOSIDE POLYMERASE INHIBITOR; NONSTRUCTURAL PROTEIN 5B; NS3 4A PROTEASE INHIBITOR; NUCLEOSIDE POLYMERASE INHIBITOR; PEGINTERFERON; PLACEBO; RIBAVIRIN; RITONAVIR; SETROBUVIR; SOFOSBUVIR; TEGOBUVIR; TELAPREVIR; UNCLASSIFIED DRUG; UNINDEXED DRUG; VALOPICITABINE; NS 5 PROTEIN, HEPATITIS C VIRUS; NS-5 PROTEIN, HEPATITIS C VIRUS; PROTEINASE INHIBITOR; VIRUS PROTEIN;

ANTIVIRAL THERAPY; ARTICLE; DRUG EFFICACY; DRUG POTENCY; DRUG SAFETY; DRUG TOLERABILITY; DRUG WITHDRAWAL; GASTROINTESTINAL TOXICITY; HEPATITIS C; HEPATITIS C VIRUS; HUMAN; IMMUNOREACTIVITY; LOW DRUG DOSE; LYMPHOCYTOPENIA; MONOTHERAPY; PROTEIN TARGETING; UNSPECIFIED SIDE EFFECT; VIRUS ASSEMBLY; VIRUS PARTICLE; VIRUS REPLICATION; DRUG ANTAGONISM; DRUG DEVELOPMENT; METHODOLOGY; REVIEW;

ANTIVIRAL AGENTS; DRUG DISCOVERY; HEPATITIS C, CHRONIC; HUMANS; PROTEASE INHIBITORS; VIRAL NONSTRUCTURAL PROTEINS;

EID: 84871118829     PISSN: 15228037     EISSN: 1534312X     Source Type: Journal    
DOI: 10.1007/s11894-012-0303-3     Document Type: Article

References (46)

1. Moradpour D, Penin F, Rice CM. Replication of hepatitis C virus. Nat Rev Microbiol. 2007;5:453-63. (Pubitemid 46780082)
2. Lesburg CA, Cable MB, Ferrari E, et al. Crystal structure of the RNA-dependent RNA polymerase from hepatitis C virus reveals a fully encircled active site. Nat Struct Biol. 1999;6:937-43. (Pubitemid 29463307)
3. Mauss S, Berg T, Rockstroh J, Sarrazin C, Wedemeyer H. Short Guide to Hepatitis C 2012 Edition; Flying Publisher & Kamps.
4. Koch U, Narjes F. Recent progress in the development of inhibitors of the hepatitis C virus RNA-dependent RNA polymerase. Curr Top Med Chem. 2007;7:1302-29. (Pubitemid 47321576)
5. Pockros P, Jensen DM, Tsai N. First SVR data with the nucleoside analogue polymerase inhibitor mericitabine (RG7128) combined with peginterferon/ ribavirin in treatment-naive HCV G1/4 patients: interim analysis of the JUMP-C trial. J Hepatol. 2011;54:538.
6. Pockros P, Jensen D, Tsai N, et al. SVR-12 among G1/4 Treatment-Naïve Patients receiving Mericitabine in Combination with PEG-IFNα-2A/RBV: Interim Analysis from the Jump-C Study. J Hepatol. 2012;56(Supplement 2):S477.
7. Gane EJ, Roberts SK, Stedman CA, et al. Oral combination therapy with a nucleoside polymerase inhibitor (RG7128) and danoprevir for chronic hepatitis C genotype 1 infection (INFORM-1): a randomised, double-blind, placebo-controlled, dose-escalation trial. Lancet. 2010;376:1467-75.
8. Gane EJ, Pockros P, Zeuzem S, et al. Interferon-Free Treatment with a combination of Mericitabine and Danoprevir/R with or without Ribavirin in Treatment-Naïve HCV Genotype 1-Infected Patients. J Hepatol. 2012;56(Supplement 2):S555.
9. Hoffmann-La Roche. ANNAPURNA: A study of the combination of RO5466731, RO5190591, ritonavir and Copegus(ribavirin) with or without RO5024048 in patients with chronic hepatitis C who are either treatment-naive or have previously experienced a null response to interferon-based treatment [ClinicalTrials.gov identifier NCT01628094]. US National Institutes of Health, ClinicalTrials.gov [online] Available from URL: http://www.clinicaltrials.gov [Accessed 2012 Aug26]
10. Nelson DR, Lalezari J, Lawitz E, et al. Once daily PSI-7977 plus PEG-IFN/ RBV in HCV GT1: 98 % rapd virologic response, complete early virologic response: the PROTON study. J Hepatol. 2011;54 suppl 1:S544. Abstract 1372.
11. Lalezari J, Lawitz E, Rodriguez-Torres M, et al. Once daily PSI-7977 plus PEGIFN/RBV in a phase 2B trial: rapid virologic suppression in treatment-naïve patients with HCV GT2/GT3. J Hepatol. 2011;54 suppl 1:S28. Abstract 61.
12. Lawitz E, Lalezari JP, Hassanein T, et al. Once-daily PSI-7977 plus peg/RBV in treatment-naive pateints with HCV GT1: robust end of treatment response rates are sustained post-treatment. Hepatology. 2011;54:113.
13. 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. 62nd Annual Meeting of the American Association for the Study of Liver Diseases November 4-8, 2011 San Francisco, CA.
14. Gane EJ, Stedman C, Anderson J, et al. 100 % Rapid Virologic Response for PSI-7977 + Ribavirin in Genotype 1 Null Responders (ELECTRON): Early Viral Decline Similar to that Observed in Genotype 1 and Genotype 2/3 Treatment-naïve Patients. 19th Conference on Retroviruses and Opportunistic Infections, March 5-8, 2012; abstract 54LB.
15. Gilead Announces Early Sustained Virologic Response Rates for GS-7977 Plus Ribavirin in Genotype 1 Treatment-Naïve Hepatitis C Patients- Interim Results Reported from ELECTRON and QUANTUM Studies. Barcelona, Spain, Apr 19, 2012.Gilead Sciences, Inc.
16. 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-naïve patients with chronic HCV GT1, 2, or 3. 47th Annual Meeting of the European Association for the Study of the Liver, April 18-22, 2012, Barcelona, Spain; LB abstract 1422.
17. http://www.clinicaltrials.gov: Hepatitis C and Gilead Sciences. August 19, 2012.
18. Bristol-Myers to Suspend a Drug Study. The New York Times, August 3, 2012.
19. Lawitz E, Poordad F, Kowdley KV, et al. A 12-week interferon- free regimen of ABT-450/r, ABT-072, and ribavirin was well tolerated and achieved sustained virologic response. 2012 Apr 18-22; Barcelona.
20. Poordad F, Lawitz E, Kowdley KV, et al. 12-Week interferon- free regimen of ABT-450/r+ABT-333+ribavirin achieved SVR12 in more than 90 % of treatment-naïve HCV non-responders [abstract no. 1399]. 47th Annual Meeting of the European Association for the Study of the Liver;2012 Apr 18-22; Barcelona.
21. Zeuzem S, Asselah T, Angus P, et al. Efficacy of the protease inhibitor BI 201335, polymerase inhibitor BI 207127, and ribavirin in patients with chronic HCV infection. Gastroenterology. 2011;141(6):2047-55.
22. Zeuzem S, Buggisch P, Agarwal K, et al. Dual, triple, and quadruple combination treatment with a protease inhibitor (GS-9256) and a polymerase inhibitor (GS-9190) alone and in combination with ribavirin (RBV) or PEGIFN/RBV for up to 28 days in treatment-naIve, genotype 1 HCV subjects [abstract no. LB1]. 61st Annual Meeting of the American Association for the Study of Liver Diseases; 2010 Oct 29-Nov 2; Boston (MA).
23. Sulkowski M, Rodriguez-Torres M, Lawitz E, et al. High sustained virologic response rate in treatment-naive HCV genotype 1a and 1b patients treated for 12 weeks with an interferon-free all-oral quad regimen: interim results [abstract no. 1421]. 47th Annual Meeting of the European Association for the Study of the Liver; 2012 Apr 18-22; Barcelona.
24. Jacobson I, Pockros P, Lalezari J, et al. Antiviral activity of Filibuvir in combination with pegylated interferon alfa-2a and ribavirin for 28 days in treatment naïve patients chronically infected with HCV genotype 1. J Hepatol. 2009;50 Suppl 1:S382.
25. Sarrazin C, Zeuzem S. Resistance to direct antiviral agents in patients with hepatitis C virus infection. Gastroenterology. 2010;138:447-62.
26. Ali S, Leveque V, Le Pogam S, et al. Selected replicon variants with low-level in vitro resistance to the hepatitis C virus NS5B polymerase inhibitor PSI-6130 lack cross-resistance with R1479. Antimicrob Agents Chemother. 2008;52:4356-69.
27. Cooper C, Lawitz E, Ghali P, et al. Antiviral activity of the non-nucleoside polymerase inhibitor, VCH-759, in chronic hepatitis C patients: Results from a randomized, double-blind, placebo-controlled, ascending multiple dose study. Hepatol. 2007;46:S864.
28. Erhardt A, Deterding K, Benhamou Y, et al. Safety, pharmacokinetics and antiviral effect of BILB 1941, a novel hepatitis C virus RNA polymerase.
29. Zeuzem S, Soriano V, Asselah T, et al. SVR4 and SVR12 with an interferon-free regimen of BI201335 and BI207127, +/- ribavirin, in treatment-naïve patients with genotype-1 HCV infection: Interim results of SOUND-C2.[ abstract no. 101] 47th Annual Meeting of the European Association for the Study of the Liver, April 18-22, 2012, Barcelona, Spain.
30. Nelson DR, Gane EJ, Jacobson IM, et al. VX- 222/telaprevir in combination with peginterferon-alfa-2a and ribavirin in treatment-naive genotype 1 HCV patients treated for12 weeks: Zenith study, SVR 12 interim analyses [abstract]. Hepatology. 2011;54:1442.
31. Lawitz E, Rodriguez-Torres M, Rustgi VK, et al.Safety and Antiviral Activity of ANA598 in Combination with Pegylated Interferon α2A Plus Ribavirin in Treatment-Naïve Genotype-1 Chronic HCV Patients.[abstract no. LB13] 45th Annual Meeting of the European Association for the Study of the Liver (EASL 2010). Vienna, Austria. April 14-18, 2010.
32. Meylan E, Curran J, Hofmann K, et al. Cardif is an adaptor protein in the RIG-I antiviral pathway and is targeted by hepatitis C virus. Nature. 2005;437:1167-72. (Pubitemid 41509355)
33. Manns M, Reesink H, Berg T, et al. Rapid viral response of once-daily TMC435 plus pegylated interferon/ribavirin in hepatitis C genotype-1 patients: a randomized trial. Antivir Ther. 2011;16:1021-33.
34. Brainard DM, Petry A, Van Dyck K, et al. Safety and antiviral activity of MK-5172, a novel HCV NS3/4A protease inhibitor with potent activity against known resistance mutants, in genotype 1 and 3 HCV-infected patients. Hepatology. 2010;52:706.
35. Reesink HW, Fanning GC, Farha KA, et al. Rapid HCV-RNA decline with once daily TMC435: a phase I study in healthy volunteers and hepatitis C patients. Gastroenterology. 2010;138:913-21.
36. Pockros PJ. Interferon free hepatitis C therapy: how close are we? Drugs. 2012;72(14):1825-31.
37. Shi ST, Polyak SJ, Tu H, Taylor DR, Gretch DR, Lai MM. Hepatitis C virus NS5A colocalizes with the core protein on lipid droplets and interacts with apolipoproteins. Virology. 2002;292:198-210. (Pubitemid 34920540)
38. Wohnsland A, Hofmann WP, Sarrazin C. Viral determinants of resistance to treatment in patients with hepatitis C. Clin Microbiol Rev. 2007;20:23-38. (Pubitemid 46167766)
39. Gao M, Nettles RE, Belema M, et al. Chemical genetics strategy identifies an HCV NS5A inhibitor with a potent clinical effect. Nature. 2010;465:96-100.
40. Hezode C, Hirschfield GM, Ghesquiere W, et al. BMS-790052, a NS5A replication complex inhibitor, combined with peginterferon alfa-2a and ribavirin in treatment-navie HCVgentoype 1 or 4 patients: phase 2b AI444010 study interim week 12 results. Hepatology. 2011;54:115.
41. Lok AS, Gardiner DF, Lawitz E, et al. Preliminary study of two antiviral agents for hepatitis C genotype 1. N Engl J Med. 2012;366(3):216-24.
42. Suzuki F, Sezaki H, Akuta N, et al. Prevalence of hepatitis C virus variants resistant to NS3 protease inhibitors or the NS5A inhibitor (BMS-790052) in hepatitis patients with genotype 1b. J Clin Virol. 2012;54(4):352-4.
43. Chayama K, Takahashi S, Kawakami Y, et al. Dual oral combination therapy with the NS5A inhibitor BMS-790052 and the NS3 protease inhibitor BMS-650032 achieved 90 % sustained virologic response (SVR12) in HCV genotype 1b-infected null responders [abstract no. LB-4]. 62nd Annual Meeting of the American Association for the Study of Liver Diseases; 2011 Nov 4-8; San Francisco (CA).
44. Flisiak R, Horban A, Gallay P, et al. The cyclophilin inhibitor Debio-025 shows potent antihepatitis C effect in patients coinfected with hepatitis C and human immunodeficiency virus. Hepatology. 2008;47:817-26. (Pubitemid 351449673)
45. Flisiak R, Feinman SV, Jablkowski M, et al. The cyclophilin inhibitor Debio 025 combined with PEG IFN alpha 2a significantly reduces viral load in treatment-naive hepatitis C patients. Hepatology. 2009;49:1460-8.
46. 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[abstract no. LB 11]. 47th Annual Meeting of the European Association for the Study of the Liver; 2012 Apr 18-22; Barcelona.