NS5B polymerase inhibitors in phase II clinical trials for HCV infection

References

• WHO Global hepatitis report, 2017. [Cited 2017 Nov 6] Available from http://www.who.int/hepatitis/publications/global-hepatitis-report2017/en/
   Google Scholar
• Zopf S, Kremer AE, Neurath MF, et al. Advances in hepatitis C therapy: what is the current state - what come’s next? World J Hepatol. 2016;8:139–147.
   PubMedGoogle Scholar
• Falade-Nwulia O, Suarez-Cuervo C, Nelson DR, et al. Oral direct-acting agent therapy for hepatitis C virus infection: a systematic review flying under the radar: the immunobiology of hepatitis C. Ann Intern Med. 2017;166:637–648.
   PubMed Web of Science ®Google Scholar
• European Association for the Study of the Liver. EASL recommendations on treatment of hepatitis C 2016. J Hepatol. 2017;66:153–194.
   PubMed Web of Science ®Google Scholar
• Recommendations for Testing, Managing, and Treating Hepatitis C. Joint panel from the American Association of the study of liver diseases and the Infectious Diseases Society of America. Cited 2017 Aug 16 Available from http://www.hcvguidelines.org/
   Google Scholar
• Scheel TKH, Rice CM. Understanding the hepatitis C virus life cycle paves the way for highly effective therapies. Nat Med. 2013;19:837–849.
   PubMed Web of Science ®Google Scholar
• Gentile I, Borgia F, Zappulo E, et al. Efficacy and safety of sofosbuvir in the treatment of chronic hepatitis C: the dawn of a New Era. Rev Recent Clin Trials. 2014;9:1–7.
   PubMedGoogle Scholar
• Gentile I, Maraolo AE, Buonomo AR, et al. The discovery of sofosbuvir: a revolution for therapy of chronic hepatitis C. Expert Opin Drug Discov. 2015;10:1363–1377.
   PubMed Web of Science ®Google Scholar
• Membreno FE, Lawitz EJ. The HCV NS5B nucleoside and non-nucleoside inhibitors. Clin Liver Dis. 2011;15:611–626.
   PubMed Web of Science ®Google Scholar
• 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.
   PubMed Web of Science ®Google Scholar
• Soriano V, Vispo E, De Mendoza C, et al. Hepatitis C therapy with HCV NS5B polymerase inhibitors. Expert Opin Pharmacother. 2013;14:1161–1170.
   PubMed Web of Science ®Google Scholar
• Gentile I, Buonomo AR, Borgia G.  Dasabuvir:  A Non-Nucleoside Inhibitor of NS5B for the Treatment of Hepatitis C Virus Infection. Rev Recent Clin Trials. 2014;9:115-123.
   Google Scholar
• Mantry PS, Pathak L. Dasabuvir (ABT333) for the treatment of chronic HCV genotype I: a new face of cure, an expert review. Expert Rev Anti Infect Ther. 2016;14:157–165.
   PubMed Web of Science ®Google Scholar
• González-Colominas E, Londoño MC, Morillas RM, et al. Potential drug-drug interactions of ombitasvir, paritaprevir/Ritonavir ± Dasabuvir ± Ribavirin in Clinical Practice. J Gastroenterol Hepatol. 2017; [Epub ahead of print].
   PubMedGoogle Scholar
• Sarrazin C. The importance of resistance to direct antiviral drugs in HCV infection in clinical practice. J Hepatol. 2016;64:486–504.
   PubMed Web of Science ®Google Scholar
• Gentile I, Maraolo AE, Niola M, et al. Limiting the access to direct-acting antivirals against HCV: an ethical dilemma. Expert Rev Gastroenterol Hepatol. 2016;10:1227–1234.
   PubMed Web of Science ®Google Scholar
• Dillon JF. Hepatitis C: what is the best treatment? J Viral Hepat. 2004;11(Suppl 1):S23–27.
   PubMedGoogle Scholar
• MK-3682 (formerly IDX21437). [Cited 2017 Aug 18]. Available from: http://bciq.biocentury.com/products/mk-3682
   Google Scholar
• Gane EJ, Pianko S, Roberts SK, et al. Safety and efficacy of an 8-week regimen of grazoprevir plus ruzasvir plus uprifosbuvir compared with grazoprevir plus elbasvir plus uprifosbuvir in participants without cirrhosis infected with hepatitis C virus genotypes 1, 2, or 3 (C-CREST-1 and C-CREST-2, part A): two randomised, phase 2, open-label trials. Lancet Gastroenterol Hepatol. 2017;2:805–881.
   PubMed Web of Science ®Google Scholar
• Lawitz E, Buti M, Vierling JM, et al. Safety and efficacy of a fixed-dose combination regimen of grazoprevir, ruzasvir, and uprifosbuvir with or without RBV in participants with and without cirrhosis with chronic hepatitis C virus GT 1, 2, or 3 infection (C-CREST-1 and C-CREST-2, part B): two randomised, phase 2, open-label trials. Lancet Gastroenterol Hepatol. 2017;2:814-823. [.
   PubMedGoogle Scholar
• Serfaty L, Pianko S, Ari ZB, et al. High sustained virologic response rates in patients with chronic hepatitis C virus GT1, 2 or 3 infection following 16 weeks of MK-3682/grazoprevir/ruzasvir plus ribavirin after having failed 8 weeks of a triplet drug regimen (Part C of C-CREST-1 & 2). J Hepatol. 2017;66(Suppl):S306–307.
   Google Scholar
• Wedemeyer H, Wyles D, Reddy R, et al. Safety and efficacy of the fixed-dose combination regimen of MK-3682/grazoprevir/ruzasvir in cirrhotic or non-cirrhotic patients with chronic HCV GT1 infection who previously failed a direct-acting antiviral regimen (C-SURGE). J Hepatol. 2017;66(Suppl):S85.
   Google Scholar
• Lawitz E, Poordad F, Anderson L, et al. C-BREEZE 1: efficacy and safety of Ruzasvir 60 mg Plus Uprifosbuvir 450 mg for 12 weeks in Adults With Chronic Hepatitis C Virus (HCV) Genotype (GT)1, 2, 3, 4, or 6 Infection. Hepatology. 2017;66(Suppl):631A.
   PubMedGoogle Scholar
• Lawitz E, Gane EJ, Feld JJ, et al. C-BREEZE 2: efficacy and safety of a two-drug direct-acting antiviral agent (DAA) regimen ruzasvir 180 mg and uprifosbuvir 450 mg for 12 weeks in adults with chronic hepatitis c virus (HCV) Genotype (GT)1, 2, 3, 4, or 6. Hepatology. 2017;66(Suppl):34A.
   Google Scholar
• Combined ruzasvir, uprifosbuvir shows suboptimal HCV pangenotypic efficacy. [Cited 2017 Nov 13]. Available from: https://www.healio.com/hepatology/hepatitis-c/news/online/%7Bb3983664-1291-4fbc-8e80-595afb160224%7D/combined-ruzasvir-uprifosbuvir-shows-suboptimal-hcv-pangenotypic-efficacy
   Google Scholar
• Merck discontinues MK-3682B and MK-3682C development programs. [Cited 2017 Nov 13]. Available from: http://investors.merck.com/news/press-release-details/2017/Merck-Discontinues-MK-3682B-and-MK-3682C-Development-Programs/default.aspx
   Google Scholar
• Radalbuvir. [Cited 2017 Aug 18]. Available from: http://en.pharmacodia.com/web/drug/1_818.html
   Google Scholar
• Lawitz E, Poordad F, Hyland RH, et al. Ledipasvir/sofosbuvir-based treatment of patients with chronic genotype-1 HCV infection and cirrhosis: results from two Phase II studies. Antivir Ther. 2016;21:679–687.
   PubMed Web of Science ®Google Scholar
• Kohli A, Kattakuzhy S, Sidharthan S, et al. Four-week direct-acting antiviral regimens in noncirrhotic patients with hepatitis C virus genotype 1 Infection: an Open-Label, nonrandomized trial. Ann Intern Med. 2015;163:899–907.
   PubMed Web of Science ®Google Scholar
• Gane EJ, Stedman CA, Hyland RH, et al. Efficacy of nucleotide polymerase inhibitor sofosbuvir plus the NS5A inhibitor ledipasvir or the NS5B non-nucleoside inhibitor GS-9669 against HCV genotype 1 infection. Gastroenterology. 2014;146:736–743.
   PubMed Web of Science ®Google Scholar
• Vijgen L, Fevery B, Jekle A, et al. In vitro virology profile of the 3 direct-acting antiviral combination of AL-335, odalasvir and simeprevir. J Hepatol. 2017;66(Suppl):S533–S534.
   Google Scholar
• Gane E, Stedman C, McClure M, et al. Short duration treatment with AL-335 and odalasvir, with or without simeprevir, in treatment naïve patients with hepatitis C infection with or without cirrhosis. J Hepatol. 2017;66(Suppl):S63–S94.
   Google Scholar
• Zeuzem S, Bourgeois S, Greenbloom S, et al. Evaluation of the efficacy and tolerability of JNJ-4178 (AL-335, odalasvir, and simeprevir) in hepatitis C virus-infected patients without cirrhosis: the Phase IIb OMEGA-1 study. Hepatology. 2017;66(Suppl):38A.
   Google Scholar
• Achillion announces presentation of data from OMEGA-1 Phase 2b trial with odalasvir, AL-335, and Simeprevir (JNJ-4178) at the 2017 Liver Meeting. Cited 2017 Nov 13. Available from: http://ir.achillion.com/releasedetail.cfm?releaseid=1044856
   Google Scholar
• Janssen to discontinue hepatitis C development program. [Cited 2017 Nov 13]. Available from: http://www.janssen.com/janssen-discontinue-hepatitis-c-development-program
   Google Scholar
• Cummings MD, Lin TI, Hu L, et al. Discovery and early development of TMC647055, a non-nucleoside inhibitor of the hepatitis C virus NS5B polymerase. J Med Chem. 2014;57:1880–1892.
   PubMed Web of Science ®Google Scholar
• Devogelaere B, Berke JM, Vijgen L, et al. TMC647055, a potent nonnucleoside hepatitis C Virus NS5B polymerase inhibitor with cross-genotypic coverage. Antimicrob Agents Chemother. 2012;56:4676–4684.
   PubMed Web of Science ®Google Scholar
• Lawitz E, Rodriguez-Torres M, Nguyen TT, et al. HELIX-2, A Phase II study of samatasvir in combination with simeprevir, low dose ritonavir-boosted TMC647055 + Ribavirin in Treatment-naïve or Interferon/ribavirin Treated, Relapsed Genotype 1 HCV-infected Subjects. J Hepatol. 2014;60(Suppl):S1941.
   Google Scholar
• Samatasvir (IDX719) in combinations with simeprevir and/or TMC647055/ritonavir with or without ribavirin for 12 weeks in participants with chronic hepatitis C infection (MK-1894-005). [Cited 2017 Aug 22]. Available from: https://clinicaltrials.gov/ct2/show/study/NCT01852604
   Google Scholar
• Bourgeois S, Van Vlierberghe H, Moreno C, et al. Efficacy, safety and pharmacokinetics of simeprevir and TMC647055/ritonavir with or without ribavirin and JNJ-56914845 in HCV genotype 1 infection. BMC Gastroenterol. 2017;17:26.
   PubMed Web of Science ®Google Scholar
• Vijgen L, Thys K, Vandebosch A, et al. Virology analysis in HCV genotype 1-infected patients treated with the combination of simeprevir and TMC647055/ritonavir, with and without ribavirin, and JNJ-56914845. Virol J. 2017;14:101.
   PubMed Web of Science ®Google Scholar
• Hagan LM, Schinazi RF. Best strategies for global HCV eradication. Liver Int. 2013;33(Suppl 1):S68–79.
   PubMedGoogle Scholar
• Harris M. Managing expense and expectation in a treatment revolution: problematizing prioritisation through an exploration of hepatitis C treatment ‘benefit. Int J Drug Policy 2017;47:161-168.
   Web of Science ®Google Scholar
• Reau N, Fried MW, Nelson DR, et al. HCV Council–critical appraisal of data: recommendations for clinical practice in a rapidly evolving therapeutic landscape. Liver Int. 2016;36:488–502.
   PubMed Web of Science ®Google Scholar
• Moradpour D, Grakoui A, Manns MP. Future landscape of hepatitis C research - Basic, translational and clinical perspectives. J Hepatol. 2016;65(1 Suppl):S143–155.
   PubMedGoogle Scholar
• 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.
   PubMed Web of Science ®Google Scholar
• Gentile I, Scotto R, Zappulo E, et al. Investigational direct-acting antivirals in hepatitis C treatment: the latest drugs in clinical development. Expert Opin Investig Drugs. 2016;25:557–572.
   PubMed Web of Science ®Google Scholar
• Kardashian AA, Pockros PJ. Novel emerging treatments for hepatitis C infection: a fast-moving pipeline. Therap Adv Gastroenterol. 2017;10:277–282.
   PubMed Web of Science ®Google Scholar
• Hopkins S, Gallay P. Cyclophilin inhibitors: an emerging class of therapeutics for the treatment of chronic hepatitis C infection. Viruses. 2012;4:2558–2577.
   PubMed Web of Science ®Google Scholar
• Borgia G, Maraolo AE, Buonomo AR, et al. The therapeutic potential of new investigational hepatitis C virus translation inhibitors. Expert Opin Investig Drugs. 2016;25:1209–1214.
   PubMed Web of Science ®Google Scholar
• Gentile I, Zappulo E, Buonomo AR, et al. Beclabuvir for the treatment of hepatitis C. Expert Opin Investig Drugs. 2015;24:1111–1121.
   PubMed Web of Science ®Google Scholar
• Toyota J, Karino Y, Suzuki F, et al. Daclatasvir/asunaprevir/beclabuvir fixed-dose combination in Japanese patients with HCV genotype 1 infection. J Gastroenterol. 2017;52:385–395.
   PubMed Web of Science ®Google Scholar
• Sulkowski MS, Flamm S, Kayali Z, et al. Short-duration treatment for chronic hepatitis C virus with daclatasvir, asunaprevir, beclabuvir and sofosbuvir (FOURward study). Liver Int. 2017;37:836–842.
   PubMed Web of Science ®Google Scholar
• Dore GJ, Feld JJ. Hepatitis C virus therapeutic development: in pursuit of “perfectovir”. Clin Infect Dis. 2015;60:1829–1836.
   PubMed Web of Science ®Google Scholar
• Horgan D, Paradiso A, McVie G, et al. Is precision medicine the route to a healthy world? Lancet. 2015;386:336–337.
   PubMed Web of Science ®Google Scholar
• Soriano V, Fernandez-Montero JV, De Mendoza C, et al. Treatment of hepatitis C with new fixed dose combinations. Expert Opin Pharmacother. 2017;18:1235–1242.
   PubMed Web of Science ®Google Scholar
• Di Maio VC, Cento V, Lenci I, et al. Multiclass HCV resistance to direct-acting antiviral failure in real-life patients advocates for tailored second-line therapies. Liver Int. 2017;37:514–528.
   PubMed Web of Science ®Google Scholar
• Nakamoto S, Kanda T, Wu S, et al. Hepatitis C virus NS5A inhibitors and drug resistance mutations. World J Gastroenterol. 2014;20:2902–2912.
   PubMed Web of Science ®Google Scholar
• Wyles D, Wedemeyer H, Ben-Ari Z, et al. Grazoprevir, Ruzasvir, and Uprifosbuvir for HCV After NS5A Treatment Failure. Hepatology. 2017; 66:1794-1804. .
   Google Scholar