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Review

Investigational direct-acting antivirals in hepatitis C treatment: the latest drugs in clinical development

, , , , &
Pages 557-572 | Received 16 Nov 2015, Accepted 29 Feb 2016, Published online: 21 Mar 2016

References

  • Wedemeyer H, Dore GJ, Ward JW. Estimates on HCV disease burden worldwide – filling the gaps. J Viral Hepat. 2015;22(Suppl 1):1–5.
  • Mohd Hanafiah K, Groeger J, Flaxman AD, et al. Global epidemiology of hepatitis C virus infection: new estimates of age-specific antibody to HCV seroprevalence. Hepatol. 2013;57:1333–1342.
  • Gentile I, Coppola N, Pasquale G, et al. A simple noninvasive score based on routine parameters can predict liver cirrhosis in patients with chronic hepatitis C. Hepat Mon. 2013;13:e8352.
  • Sagnelli E, Pisaturo M, Stanzione M, et al. Presentation, outcomes, and response to therapy among patients with acute exacerbation of chronic hepatitis C. Clin Gastroenterol Hepatol. 2013;13:00466–7.
  • Coppola N, Zampino R, Bellini G, et al. Association between a polymorphism in cannabinoid receptor 2 and severe necroinflammation in patients with chronic hepatitis C. Clin Gastroenterol Hepatol. 2013;21:00687–3.
  • Gentile I, Meola M, Buonomo AR, et al. Human platelet antigen-3 genotype predicts platelet count in patients with HCV infection. In Vivo. 2013;27:773–777.
  • Maasoumy B, Wedemeyer H. Natural history of acute and chronic hepatitis C. Best Pract Res Clin Gastroenterol. 2012;26:401–412.
  • Coppola N, Gentile I, Pasquale G, et al. Anti-HBc positivity was associated with histological cirrhosis in patients with chronic hepatitis C. Ann Hepatol. 2014;13:20–26.
  • Gentile I, Viola C, Graf M, et al. A simple noninvasive score predicts gastroesophageal varices in patients with chronic viral hepatitis. J Clin Gastroenterol. 2009;43:81–87.
  • Fortunato G, Castaldo G, Oriani G, et al. Multivariate discriminant function based on six biochemical markers in blood can predict the cirrhotic evolution of chronic hepatitis. Clin Chem. 2001;47:1696–1700.
  • Zampino R, Pisaturo MA, Cirillo G, et al. Hepatocellular carcinoma in chronic HBV-HCV co-infection is correlated to fibrosis and disease duration. Ann Hepatol. 2015;14:75–82.
  • Gentile I, Di Flumeri G, Scarica S, et al. Acute hepatitis C in patients undergoing hemodialysis: experience with high-dose interferon therapy. Minerva Urol Nefrol. 2013;65:83–84.
  • Coppola N, Marrone A, Pisaturo M, et al. Role of interleukin 28-B in the spontaneous and treatment-related clearance of HCV infection in patients with chronic HBV/HCV dual infection. Eur J Clin Microbiol Infect Dis. 2014;33:559–567.
  • Gentile I, Borgia G. Surrogate endpoints and non-inferiority trials in chronic viral hepatitis. J Hepatol. 2010;52:778.
  • McHutchison JG, Everson GT, Gordon SC, et al. Telaprevir with peginterferon and ribavirin for chronic HCV genotype 1 infection. N Engl J Med. 2009;360:1827–1838.
  • Poordad F, McCone J Jr., Bacon BR, et al. Boceprevir for untreated chronic HCV genotype 1 infection. N Engl J Med. 2011;364:1195–1206.
  • Bacon BR, Gordon SC, Lawitz E, et al. Boceprevir for previously treated chronic HCV genotype 1 infection. N Engl J Med. 2011;364:1207–1217.
  • Venkatraman S, Bogen SL, Arasappan A, et al. Discovery of (1R,5S)-N-[3-amino-1-(cyclobutylmethyl)-2,3-dioxopropyl]- 3-[2(S)-[[[(1,1-dimethylethyl)amino]carbonyl]amino]-3,3-dimethyl-1-oxobutyl]- 6,6-dimethyl-3-azabicyclo[3.1.0]hexan-2(S)-carboxamide (SCH 503034), a selective, potent, orally bioavailable hepatitis C virus NS3 protease inhibitor: a potential therapeutic agent for the treatment of hepatitis C infection. J Med Chem. 2006;49:6074–6086.
  • Tong X, Chase R, Skelton A, et al. Identification and analysis of fitness of resistance mutations against the HCV protease inhibitor SCH 503034. Antiviral Res. 2006;70:28–38.
  • Lin C, Kwong AD, Perni RB. Discovery and development of VX-950, a novel, covalent, and reversible inhibitor of hepatitis C virus NS3.4A serine protease. Infect Disord Drug Targets. 2006;6:3–16.
  • Borgia G, Reynaud L, Gentile I, et al. Case report: pernicious anemia during IFN-α treatment for chronic hepatitis C. J Interferon Cytokine Res. 2003;23:11–12.
  • Borgia G, Reynaud L, Gentile I, et al. Myasthenia gravis during low-dose IFN-α therapy for chronic hepatitis C. J Interferon Cytokine Res. 2001;21:469–470.
  • Gentile I, Viola C, Reynaud L, et al. Case report: hemolytic anemia during pegylated IFN-α2b plus ribavirin treatment for chronic hepatitis C: ribavirin is not always the culprit. J Interferon Cytokine Res. 2005;25:283–285.
  • Tosone G, Borgia G, Gentile I, et al. A case of pegylated interferon alpha-related diabetic ketoacidosis: can this complication be avoided? Acta Diabetol. 2007;44:167–169.
  • Hezode C, Fontaine H, Dorival C, et al. Triple therapy in treatment-experienced patients with HCV-cirrhosis in a multicentre cohort of the French early access programme (ANRS CO20-CUPIC) - NCT01514890. J Hepatol. 2013;59:434–441.
  • D’Ambrosio R, Colombo M. Safety of direct antiviral agents in real life. Dig Liver Dis. 2013;30:012.
  • De Clercq E. Current race in the development of DAAs (direct-acting antivirals) against HCV. Biochem Pharmacol. 2014;89:441–452.
  • Gentile I, Buonomo AR, Borgia F, et al. Ledipasvir: a novel synthetic antiviral for the treatment of HCV infection. Expert Opin Investig Drugs. 2014;23:561–571.
  • Gentile I, Buonomo AR, Borgia F, et al. MK-5172: a second-generation protease inhibitor for the treatment of hepatitis C virus infection. Expert Opin Investig Drugs. 2014;23:719–728.
  • Gentile I, Coppola N, Buonomo AR, et al. Investigational nucleoside and nucleotide polymerase inhibitors and their use in treating hepatitis C virus. Expert Opin Investig Drugs. 2014;23:1211–1223.
  • Gentile I, Buonomo AR, Zappulo E, et al. Discontinued drugs in 2012-2013: hepatitis C virus infection. Expert Opin Investig Drugs. 2015;24:239–251.
  • Gentile I, Buonomo AR, Zappulo E, et al. Interferon-free therapies for chronic hepatitis C: toward a hepatitis C virus-free world? Expert Rev Anti Infect Ther. 2014;12:763–773.
  • Gentile I, Borgia G, A pill a day keeps HCV away. Lancet Infect Dis. 2015;15:616–617.
  • Gane EJ, Stedman CA, Hyland RH, et al. Nucleotide polymerase inhibitor sofosbuvir plus ribavirin for hepatitis C. N Engl J Med. 2013;368:34–44.
  • Gentile I, Borgia F, Coppola N, et al. Daclatasvir: the first of a new class of drugs targeted against hepatitis C virus NS5A. Curr Med Chem. 2014;21:1391–1404.
  • Stedman CA. Current prospects for interferon-free treatment of hepatitis C in 2012. J Gastroenterol Hepatol. 2013;28:38–45.
  • Gallay PA, Lin K. Profile of alisporivir and its potential in the treatment of hepatitis C. Drug Des Devel Ther. 2013;7:105–115.
  • Svarovskaia ES, Dvory-Sobol H, Parkin N, et al. Infrequent development of resistance in genotype 1-6 hepatitis C virus-infected subjects treated with sofosbuvir in phase 2 and 3 clinical trials. Clin Infect Dis. 2014;59:1666–1674.
  • Lawitz EJ, Gruener D, Hill JM, et al. A phase 1, randomized, placebo-controlled, 3-day, dose-ranging study of GS-5885, an NS5A inhibitor, in patients with genotype 1 hepatitis C. J Hepatol. 2012;57:24–31.
  • Mogalian E, Mathias A, Brainard D, et al. P0712 : the pharmacokinetics of GS-5816, a pangenotypic HCV-specific NS5A inhibitor, in HCV-uninfected subjects with severe renal impairment. J Hepatol. 2015;62:SS590–1.
  • Mogalian E, Mathias A, Brainard D, et al. P742 the pharmacokinetics of VEL, a pan-genotypic HCV Ns5a inhibitor, in HCV-uninfected subjects with moderate and severe hepatic impairment. J Hepatol. 2014;60:S317.
  • Gilead, Sciences. Press release: Gilead announces phase 2 results for two investigational all-oral sofosbuvir-based regimens for the treatment of chronic hepatitis C; 2014 [ cited 2015 Nov 13]. Available from: http://www.gilead.com/news/press-releases/2014/4/gilead-announces-phase-2-results-for-two-investigational-alloral-sofosbuvirbased-regimens-for-the-treatment-of-chronic-hepatitis-c
  • Gilead, Sciences. Press release: gilead announces phase 2 data for investigational all-oral regimen of sofosbuvir plus GS-5816 for the treatment of chronic hepatitis C; 2014 [ cited 2015 Nov 13]. Available from: http://www.gilead.com/news/press-releases/2014/11/gilead-announces-phase-2-data-for-investigational-alloral-regimen-of-sofosbuvir-plus-gs5816-for-the-treatment-of-chronic-hepatitis-c#sthash.fvUszI56.dpuf
  • Feld JJ, Jacobson IM, Hezode C, et al. Sofosbuvir and velpatasvir for HCV genotype 1, 2, 4, 5, and 6 infection. N Engl J Med. 2015;373:2599–2607.
  • Foster GR, Afdhal N, Roberts SK, et al. Sofosbuvir and velpatasvir for HCV genotype 2 and 3 infection. N Engl J Med. 2015;373:2608–2617.
  • Curry MP, O’Leary JG, Bzowej N, et al. Sofosbuvir and velpatasvir for HCV in patients with decompensated cirrhosis. N Engl J Med. 2015;373:2618–2628.
  • Gilead, Sciences. Report: gilead announces data for investigational, All-oral, pan-genotypic three-drug regimen of sofosbuvir, VEL and GS-9857 for chronic hepatitis C; 2015 [ cited 2015 No v 13]. Available from: http://phx.corporate-ir.net/External.File?t=2&item=g7rqBLVLuv81UAmrh20MpywheWEscWlCEvwH.
  • Gilead, Sciences; 2015 [ cited 2015 Nov 13]. Available from: https://clinicaltrials.gov/ct2/show/results/NCT02536313
  • Yang G, Wiles J, Patel D, et al. 845 preclinical characteristics of ach-3102: a novel HCV Ns5a inhibitor with improved potency against genotype-1a virus and variants resistant to 1St generation of Ns5a inhibitors. European association for the study of the liver. J Hepatol. 2012;56:S330.
  • Muir AHJ, Hill J, Lawitz E, et al. 876 ACH-3102, a second generation NS5A inhibitor, demonstrates potent antiviral activity in patients with genotype 1a HCV infection despite the presence of baseline NS5A-resistant variants. J Hepatol. 2013;58:S360.
  • Gane E, Schwabe C, Mader M, et al. LP06 : sustained virologic response after ACH-3102 and sofosbuvir treatment for 8 or 6 weeks: a phase 2 “proxy” study. Elsevier. J Hepatol. 2015;62:S266.
  • Patel D, Zhao Y, Fabrycki J, et al. P0805 : achievement of SVR12 despite the presence of HCV variants resistant to first generation NS5A inhibitors in genotype-1 hepatitis C patients after 8-week therapy of ACH-3102 in combination with sofosbuvir. Elsevier. J Hepatol. 2015;62:S636.
  • Esmat G, El Raziky M, Gomaa A, et al. High virologic response rate in Egyptian HCV-genotype 4 patients treated with ravidasvir (PPI-668) and sofosbuvir: results of a large multicenter phase 3 registrational trial. In: Annual Meeting of the American Association for the study of liver diseases. San Francisco (CA); 2015. [cited 2016 Mar 14]. Available from: http://www.natap.org/2016/CROI/croi_101.htm
  • Lalezar JP, Holland L, Glutzer E, et al. Rapid and consistent virologic responses in a phase 2 trial of a new all-oral combination of faldaprevir, deleobuvir, and PPI-668, with and without ribavirin, in patients with HCV genotype-1a infection. AASLD Oral Presentation. Hepatol. 2013;58:36A–91A. Oral LB-20.
  • McPhee F, Sheaffer AK, Friborg J, et al. Preclinical profile and characterization of the hepatitis C virus NS3 protease inhibitor asunaprevir (BMS-650032). Antimicrob Agents Chemother. 2012;56:5387–5396.
  • Soumana DI, Ali A, Schiffer CA. Structural analysis of asunaprevir resistance in HCV NS3/4A protease. ACS Chem Biol. 2014;9:2485–2490.
  • Chayama K, Takahashi S, Toyota J, et al. Dual therapy with the nonstructural protein 5A inhibitor, daclatasvir, and the nonstructural protein 3 protease inhibitor, asunaprevir, in hepatitis C virus genotype 1b-infected null responders. Hepatol. 2012;55:742–748.
  • Mosure KW, Knipe JO, Browning M, et al. Preclinical pharmacokinetics and in vitro metabolism of asunaprevir (BMS-650032), a potent hepatitis C virus NS3 protease inhibitor. J Pharm Sci. 2015;104:2813–2823.
  • Eley T, He B, Chang I, et al. The effect of hepatic impairment on the pharmacokinetics of asunaprevir, an HCV NS3 protease inhibitor. Antivir Ther. 2015;20:29–37.
  • Garimella T, He B, Luo W-L, et al. Asunaprevir pharmacokinetics and safety in subjects with impaired renal function. Hepatol. 2013;58:430A–A.
  • Pasquinelli C, McPhee F, Eley T, et al. Single- and multiple-ascending-dose studies of the NS3 protease inhibitor asunaprevir in subjects with or without chronic hepatitis C. Antimicrob Agents Chemother. 2012;56:1838–1844.
  • Bronowicki J-P, Pol S, Thuluvath PJ, et al. Randomized study of asunaprevir plus pegylated interferon-α and ribavirin for previously untreated genotype 1 chronic hepatitis C. Antivir Ther. 2013;18:885–893.
  • Bronowicki J-P, Ratziu V, Gadano A, et al. 1420 asunaprevir with peginterferon-alfa and ribavirin in treatment-naive patients with genotype-1 OR −4 chronic hepatitis C: SVR24 results from a randomized phase 2B study (AI447016). J Hepatol. 2013;58:SS571-SS572.
  • Vierling JM, Lataillade M, Gane EJ, et al. Sustained virologic response (SVR12) in HCV genotype 1 patients receiving peginterferon lambda in combination with ribavirin and either daclatasvir or asunaprevir: interim results from the D-LITE study. Hepatol. 2012;56:1522–1523.
  • Jensen D, Sherman KE, Hezode C, et al. Daclatasvir and asunaprevir plus peginterferon alfa and ribavirin in HCV genotype 1 or 4 non-responders. J Hepatol. 2015;63:30–37.
  • Piroth L, Paniez H, Taburet AM, et al. High cure rate with 24 weeks of daclatasvir-based quadruple therapy in treatment-experienced, null-responder patients with HIV/hepatitis C virus genotype 1/4 coinfection: the ANRS HC30 QUADRIH study. Clinical infectious diseases: an official publication of the Infectious Diseases Society of America. Clin Infect Dis. 2015;61:817–825.
  • Lok AS, Gardiner DF, Lawitz E, et al. Preliminary study of two antiviral agents for hepatitis C genotype 1. N Engl J Med. 2012;366:216–224.
  • Lok AS, Gardiner DF, Hezode C, et al. Randomized trial of daclatasvir and asunaprevir with or without PegIFN/RBV for hepatitis C virus genotype 1 null responders. J Hepatol. 2014;60:490–499.
  • Suzuki Y, Ikeda K, Suzuki F, et al. Dual oral therapy with daclatasvir and asunaprevir for patients with HCV genotype 1b infection and limited treatment options. J Hepatol. 2013;58:655–662.
  • Kumada H, Suzuki Y, Ikeda K, et al. Daclatasvir plus asunaprevir for chronic HCV genotype 1b infection. Hepatol. 2014;6:27113.
  • Manns M, Pol S, Jacobson I. All-oral dual therapy with daclatasvir and asunaprevir in patients with HCV genotype 1B infection: phase 3 study results. J Hepatol. 2014;60:S524–S5.
  • Manns M, Pol S, Jacobson IM, et al. All-oral daclatasvir plus asunaprevir for hepatitis C virus genotype 1b: a multinational, phase 3, multicohort study. Lancet. 2014;384:1597–1605.
  • Nakamuta M, Kohjima M, Motomura K, et al. Early HCV kinetics during dual oral therapy with daclatasvir and asunaprevir. J Hepatol. Vienna; 2015;62:S648–S649.
  • Lemm JA, Liu M, Gentles RG, et al. Preclinical characterization of BMS-791325, an allosteric inhibitor of hepatitis C virus NS5B polymerase. Antimicrob Agents Chemother. 2014;58:3485–3495.
  • Liu M, Tuttle M, Gao M, et al. Potency and resistance analysis of hepatitis C virus NS5B polymerase inhibitor BMS-791325 on all major genotypes. Antimicrob Agents Chemother. 2014;58:7416–7423.
  • Sims KD, Lemm J, Eley T, et al. Randomized, placebo-controlled, single-ascending-dose study of BMS-791325, a hepatitis C virus (HCV) NS5B polymerase inhibitor, in HCV genotype 1 infection. Antimicrob Agents Chemother. 2014;58:3496–3503.
  • Tatum H, Thuluvath PJ, Lawitz E, et al. A randomized, placebo-controlled study of the NS5B inhibitor beclabuvir with peginterferon/ribavirin for HCV genotype 1. J Viral Hepat. 2015;22:658–664.
  • Tatum H, Thuluvath P, Lawitz E, et al. Safety and efficacy of BMS-791325, a non-nucleoside NS5B polymerase inhibitor, combined with peginterferon alfa-2a and ribavirin in treatment-naive patients infected with hepatitis C virus genotype 1. AASLD Poster. Hepatol. 2013;58:141A. P1126.
  • Everson GT, Sims KD, Rodriguez-Torres M, et al. Efficacy of an interferon- and ribavirin-free regimen of daclatasvir, asunaprevir, and BMS-791325 in treatment-naive patients with HCV genotype 1 infection. Gastroenterol. 2014;146:420–429.
  • Everson G, Sims KD, Thuluvath PJ, et al. Daclatasvir in combination with asunaprevir and beclabuvir for prior null responders with chronic HCV genotype 1 infection. AASLD Poster. Hepatology. 2014; 60:188A. P1943.
  • Everson G, Sims KD, Thuluvath PJ, et al. Daclatasvir in combination with asunaprevir and beclabuvir for prior null responders with chronic HCV genotype 1 infection. Poster presented at:. The Liver Meeting® 2014, the 65th Annual Meeting of the American Association for the Study of Liver Diseases (AASLD); 2014 Nov 7–11; Boston (MA). Poster 1943.
  • Hassanein T, Sims KD, Bennett M, et al. A randomized trial of daclatasvir in combination with asunaprevir and beclabuvir in patients with chronic hepatitis C virus genotype 4 infection. J Hepatol. 2015;62:1204–1206.
  • Poordad F, Sievert W, Mollison L, et al. Fixed-dose combination therapy with daclatasvir, asunaprevir, and beclabuvir for noncirrhotic patients with HCV genotype 1 infection. JAMA: J Am Med Assoc. 2015;313:1728–1735.
  • Muir AJ, Poordad F, Lalezari J, et al. Daclatasvir in combination with asunaprevir and beclabuvir for hepatitis C virus genotype 1 infection with compensated cirrhosis. JAMA: J Am Med Assoc. 2015;313:1736–1744.
  • Everson GT, Sims KD, Thuluvath PJ, et al. Daclatasvir + asunaprevir + beclabuvir ± ribavirin for chronic HCV genotype 1-infected treatment-naive patients. Liver Int. 2016;36:189–197.
  • Adamczyk R, Sims K, Hesney M. The effect of renal impairment on multiple-dose pharmacokinetics of the fixed-dose combination of daclatasvir/asunaprevir/beclabuvir. J Hepatol. 2015;62:S628. P0790.
  • Summa V, Ludmerer SW, McCauley JA, et al. MK-5172, a selective inhibitor of hepatitis C virus NS3/4a protease with broad activity across genotypes and resistant variants. Antimicrob Agents Chemother. 2012;56:4161–4167.
  • Harper S, McCauley JA, Rudd MT, et al. Discovery of MK-5172, a macrocyclic hepatitis C virus NS3/4a protease inhibitor. ACS Med Chem Lett. 2012;3:332–336.
  • Manns MP, Vierling JM, Bacon BR, et al. The combination of MK-5172, peginterferon, and ribavirin is effective in treatment-naive patients with hepatitis C virus genotype 1 infection without cirrhosis. Gastroenterol. 2014;147:366-76.e6.
  • Lagging M, Brown A, Mantry PS, et al. Grazoprevir plus peginterferon and ribavirin in treatment-naive patients with hepatitis C virus genotype 1 infection: a randomized trial. J Viral Hepa. 2016;23:80–88.
  • Sulkowski M, Hezode C, Gerstoft J, et al. Efficacy and safety of 8 weeks versus 12 weeks of treatment with grazoprevir (MK-5172) and elbasvir (MK-8742) with or without ribavirin in patients with hepatitis C virus genotype 1 mono-infection and HIV/hepatitis C virus co-infection (C-WORTHY): a randomised, open-label phase 2 trial. Lancet. 2015;385:1087–1097.
  • Lawitz E, Gane E, Pearlman B, et al. Efficacy and safety of 12 weeks versus 18 weeks of treatment with grazoprevir (MK-5172) and elbasvir (MK-8742) with or without ribavirin for hepatitis C virus genotype 1 infection in previously untreated patients with cirrhosis and patients with previous null response with or without cirrhosis (C-WORTHY): a randomised, open-label phase 2 trial. Lancet. 2015;385:1075–1086.
  • Buti M, Gordon SC, Zuckerman E, et al. Grazoprevir, elbasvir, and ribavirin for chronic hepatitis C virus genotype 1 Infection after failure of pegylated interferon and ribavirin with an earlier-genera- tion protease inhibitor: final 24-week results from C-SALVAGE. Clin Infect Dis. 2016;62:32–36.
  • Zeuzem S, Ghalib R, Reddy KR, et al. Grazoprevir-elbasvir combination therapy for treatment-naive cirrhotic and noncirrhotic patients with chronic hepatitis C virus genotype 1, 4, or 6 infection: a randomized trial. Ann Intern Med. 2015;163:1–13.
  • Roth D, Nelson DR, Bruchfeld A, et al. Grazoprevir plus elbasvir in treatment-naive and treatment-experienced patients with hepatitis C virus genotype 1 infection and stage 4-5 chronic kidney disease (the C-SURFER study): a combination phase 3 study. Lancet. 2015;386:1537–1545.
  • Yee BE, Nguyen NH, Zhang B, et al. Sustained virological response and its treatment predictors in hepatitis C virus genotype 4 compared to genotypes 1, 2, and 3: a meta-analysis. BMJ Open Gastroenterol. 2015;2:e000049.
  • Sulkowski MS, Cooper C, Hunyady B, et al. Management of adverse effects of Peg-IFN and ribavirin therapy for hepatitis C. Nat Rev Gastroenterol Hepatol. 2011;8:212–223.
  • Vierling JM, Zeuzem S, Poordad F, et al. Safety and efficacy of boceprevir/peginterferon/ribavirin for HCV G1 compensated cirrhotics: meta-analysis of 5 trials. J Hepatol. 2014;61:200–209.
  • Yang D, Liang HJ, Li D, et al. The efficacy and safety of telaprevir-based regimens for treating chronic hepatitis C virus genotype 1 infection: a meta-analysis of randomized trials. Intern Med. 2013;52:653–660.
  • Gentile I, Carleo MA, Borgia F, et al. The efficacy and safety of telaprevir - a new protease inhibitor against hepatitis C virus. Expert Opin Investig Drugs. 2010;19:151–159.
  • Sullivan JC, De Meyer S, Bartels DJ, et al. Evolution of treatment-emergent resistant variants in telaprevir phase 3 clinical trials. Clin Infect Dis. 2013;57:221–229.
  • Lenz O, Verbinnen T, Fevery B, et al. Virology analyses of HCV isolates from genotype 1-infected patients treated with simeprevir plus peginterferon/ribavirin in phase IIb/III studies. J Hepatol. 2015;62:1008–1014.
  • Barnard RJ, Howe JA, Ogert RA, et al. Analysis of boceprevir resistance associated amino acid variants (RAVs) in two phase 3 boceprevir clinical studies. Virology. 2013;444:329–336.
  • Sarrazin C, Dvory-Sobol H, Svarovskaia ES, et al. Baseline and post-baseline resistance analyses of phase 2/3 studies of ledipasvir/sofosbuvir RBV. Hepatol. 2014;60:1128A.
  • Poordad F, Sievert W, Mollison L. All-oral, fixed-dose combination therapy with daclatasvir/asunaprevir/beclabuvir for non-cirrhotic patients with chronic HCV genotype 1 infection: UNITY-1 phase 3 SVR12 results. Poster presented at The Liver Meeting 2014, the 65th Annual Meeting of the American Association for the Study of Liver Diseases (AASLD); 2014 Nov 7–11; Boston (MA). Poster LB-7.
  • Muir A, Poordad F, Lalezari J, et al. All-oral fixed-dose combination therapy with daclatasvir/asunaprevir/beclabuvir, ± ribavirin, for patients with chronic HCV genotype 1 infection and compensated cirrhosis: UNITY-2 phase 3 SVR12 results. AASLD Oral presentation. Hepatol. 2014;60: 32A–91A.Oral LB-2.

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