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International Journal of Hepatology
Volume 2016, Article ID 3852126, 8 pages
http://dx.doi.org/10.1155/2016/3852126
Review Article

Elbasvir/Grazoprevir: A Review of the Latest Agent in the Fight against Hepatitis C

1Department of Pharmacy Practice, University of Mississippi School of Pharmacy, Jackson, MS 39216, USA
2Department of Medicine-Infectious Diseases, University of Mississippi Medical Center, Jackson, MS 39216, USA

Received 30 March 2016; Accepted 24 May 2016

Academic Editor: Maria Buti

Copyright © 2016 Allison M. Bell et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Linked References

  1. WHO Fact Sheet, 2016, http://www.who.int/mediacentre/factsheets/fs164/en.
  2. A. J. Zuckerman, “The elusive hepatitis C virus,” British Medical Journal, vol. 299, no. 6704, pp. 871–873, 1989. View at Publisher · View at Google Scholar · View at Scopus
  3. F. Douam, Q. Ding, and A. Ploss, “Recent advances in understanding hepatitis C,” F1000Research, vol. 5, article 131, 2016. View at Publisher · View at Google Scholar
  4. S. Zopf, A. E. Kremer, M. F. Neurath, and J. Siebler, “Advances in hepatitis C therapy: what is the current state—what come's next?” World Journal of Hepatology, vol. 8, no. 3, pp. 139–147, 2016. View at Publisher · View at Google Scholar
  5. K. S. Gutfreund and V. G. Bain, “Chronic viral hepatitis C: management update,” Canadian Medical Association Journal, vol. 162, no. 6, pp. 827–833, 2000. View at Google Scholar · View at Scopus
  6. P. Klenerman and P. K. Gupta, “Hepatitis C virus: current concepts and future challenges,” QJM, vol. 105, no. 1, pp. 29–32, 2012. View at Publisher · View at Google Scholar · View at Scopus
  7. T. Asselah, N. Boyer, D. Saadoun, M. Martinot-Peignoux, and P. Marcellin, “Direct-acting antivirals for the treatment of hepatitis C virus infection: optimizing current IFN-free treatment and future perspectives,” Liver International, vol. 36, pp. 47–57, 2016. View at Publisher · View at Google Scholar
  8. X. Zhang, “Direct anti-HCV agents,” Acta Pharmaceutica Sinica B, vol. 6, no. 1, pp. 26–31, 2016. View at Publisher · View at Google Scholar
  9. Zepatier, (Elbasvir and Grazoprevir) Tablets for Oral Use, Merck & Co, Whitehouse Station, NJ, USA, 2016.
  10. G. M. Keating, “Elbasvir/Grazoprevir: first global approval,” Drugs, vol. 76, no. 5, pp. 617–624, 2016. View at Publisher · View at Google Scholar
  11. D. Roth, D. R. Nelson, A. Bruchfeld 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,” The Lancet, vol. 386, no. 10003, pp. 1537–1545, 2015. View at Google Scholar
  12. J. K. Rockstroh, M. Nelson, C. Katlama et al., “Efficacy and safety of grazoprevir (MK-5172) and elbasvir (MK-8742) in patients with hepatitis C virus and HIV co-infection (C-EDGE CO-INFECTION): a non-randomised, open-label trial,” Lancet HIV, vol. 2, no. 8, pp. e319–e327, 2015. View at Publisher · View at Google Scholar
  13. S. Zeuzem, R. Ghalib, K. R. Reddy 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,” Annals of Internal Medicine, vol. 163, no. 1, pp. 1–13, 2015. View at Publisher · View at Google Scholar · View at Scopus
  14. M. Lagging, A. Brown, P. S. Mantry et al., “Grazoprevir plus peginterferon and ribavirin in treatment-naive patients with hepatitis C virus genotype 1 infection: a randomized trial,” Journal of Viral Hepatitis, vol. 23, no. 2, pp. 80–88, 2016. View at Publisher · View at Google Scholar · View at Scopus
  15. E. Lawitz, E. Gane, B. Pearlman 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,” The Lancet, vol. 385, no. 9973, pp. 1075–1086, 2015. View at Publisher · View at Google Scholar · View at Scopus
  16. M. Houghton, “Discovery of the hepatitis C virus,” Liver International, vol. 29, supplement 1, pp. 82–88, 2009. View at Publisher · View at Google Scholar · View at Scopus
  17. D. B. Smith, J. Bukh, C. Kuiken et al., “Expanded classification of hepatitis C virus into 7 genotypes and 67 subtypes: updated criteria and genotype assignment web resource,” Hepatology, vol. 59, no. 1, pp. 318–327, 2014. View at Publisher · View at Google Scholar · View at Scopus
  18. AASLD-IDSA, “Recommendations for testing, managing, and treating hepatitis C,” 2016, http://www.hcvguidelines.org.
  19. J. P. Messina, I. Humphreys, A. Flaxman et al., “Global distribution and prevalence of hepatitis C virus genotypes,” Hepatology, vol. 61, no. 1, pp. 77–87, 2015. View at Publisher · View at Google Scholar · View at Scopus
  20. P. Deming, M. T. Martin, J. Chan et al., “Therapeutic advances in HCV genotype 1 infection: insights from the society of infectious diseases pharmacists,” Pharmacotherapy, vol. 36, no. 2, pp. 203–217, 2016. View at Publisher · View at Google Scholar
  21. J. Ampuero and M. Romero-Gomez, “Hepatitis C virus current and evolving treatments for genotypes 2 and 3,” Gastroenterology Clinics of North America, vol. 44, no. 4, pp. 845–857, 2015. View at Google Scholar
  22. E. Gower, C. Estes, S. Blach, K. Razavi-Shearer, and H. Razavi, “Global epidemiology and genotype distribution of the hepatitis C virus infection,” Journal of Hepatology, vol. 61, supplement 1, pp. S45–S57, 2014. View at Publisher · View at Google Scholar · View at Scopus
  23. T. Y. Abdel-Ghaffar, M. M. Sira, and S. E. Naghi, “Hepatitis C genotype 4: the past, present and future,” World Journal of Hepatology, vol. 7, no. 28, pp. 2792–2810, 2015. View at Publisher · View at Google Scholar
  24. H. E. M. Smuts and J. Kannemeyer, “Genotyping of hepatitis C virus in South Africa,” Journal of Clinical Microbiology, vol. 33, no. 6, pp. 1679–1681, 1995. View at Google Scholar · View at Scopus
  25. M. H. Nguyen and E. B. Keeffe, “Prevalence and treatment of hepatitis C virus genotypes 4, 5, and 6,” Clinical Gastroenterology and Hepatology, vol. 3, no. 2, pp. S97–S101, 2005. View at Publisher · View at Google Scholar · View at Scopus
  26. K. A. Naamani, S. A. Sinani, and M. Deschenes, “Epidemiology and treatment of hepatitis C genotypes 5 and 6,” Canadian Journal of Gastroenterology, vol. 27, no. 1, pp. e8–e12, 2013. View at Google Scholar
  27. E. Lawitz, J. P. Lalezari, T. Hassanein et al., “Sofosbuvir in combination with peginterferon alfa-2a and ribavirin for non-cirrhotic, treatment-naive patients with genotypes 1, 2, and 3 hepatitis C infection: a randomised, double-blind, phase 2 trial,” The Lancet Infectious Diseases, vol. 13, no. 5, pp. 401–408, 2013. View at Publisher · View at Google Scholar · View at Scopus
  28. M. Mizokami, O. Yokosuka, T. Takehara et al., “Ledipasvir and sofosbuvir fixed-dose combination with and without ribavirin for 12 weeks in treatment-naïve and previously treated Japanese patients with genotype 1 hepatitis C: an open-label, randomised, phase 3 trial,” The Lancet Infectious Diseases, vol. 15, no. 6, pp. 645–653, 2015. View at Publisher · View at Google Scholar · View at Scopus
  29. F. Poordad, C. Hezode, R. Trinh et al., “ABT-450/r-ombitasvir and dasabuvir with ribavirin for hepatitis C with cirrhosis,” The New England Journal of Medicine, vol. 370, no. 21, pp. 1973–1982, 2014. View at Publisher · View at Google Scholar · View at Scopus
  30. E. Lawitz, M. S. Sulkowski, R. Ghalib et al., “Simeprevir plus sofosbuvir, with or without ribavirin, to treat chronic infection with hepatitis C virus genotype 1 in non-responders to pegylated interferon and ribavirin and treatment-naive patients: the COSMOS randomised study,” The Lancet, vol. 384, no. 9956, pp. 1756–1765, 2014. View at Publisher · View at Google Scholar · View at Scopus
  31. B. L. Pearlman, C. Ehleben, and M. Perrys, “The combination of simeprevir and sofosbuvir is more effective than that of peginterferon, ribavirin, and sofosbuvir for patients with hepatitis C-related child's class a cirrhosis,” Gastroenterology, vol. 148, no. 4, pp. 762–770, 2015. View at Publisher · View at Google Scholar · View at Scopus
  32. M. S. Sulkowski, D. F. Gardiner, M. Rodriguez-Torres et al., “Daclatasvir plus sofosbuvir for previously treated or untreated chronic HCV infection,” The New England Journal of Medicine, vol. 370, no. 3, pp. 211–221, 2014. View at Publisher · View at Google Scholar
  33. D. H. Spach and H. N. Kim, “Medications to treat HCV,” http://www.hepatitisc.uw.edu/page/treatment/drugs.
  34. A. Brown, C. Hezode, E. Zuckerman et al., “C-SCAPE: efficacy and safety of 12 weeks of grazoprevir ± elbasvir ± ribavirin in patients with HCV GT2, 4, 5, or 6 infection,” in Proceedings of the 50th Annual Meeting of the European Association for the Study of the Liver, Abstract P0771, Vienna, Austria, April 2015.
  35. F. Poordad, E. Lawitz, J. Gutierrez et al., “C-SWIFT: grazoprevir/elbasvir + sofosbuvir in cirrhotic and noncirrhotic, treatment-naïve patients with hepatitis C virus genotype 1 infection, for durations of 4, 6, or 8 weeks and genotype 3 infection for durations of 8 or 12 weeks,” in Proceedings of the 50th Annual Meeting of the European Association for the Study of the Liver, Abstract O006, Vienna, Austria, April 2015.
  36. ClinicalTrials.gov, http://www.clinicaltrials.gov.
  37. I. M. Jacobsen, F. Poordad, R. Firpi-Morell et al., “Efficacy and safety of grazoprevir and elbasvir in hepatitis C genotype 1-infected patients with Child-Pugh class B cirrhosis (C-SALT),” in Proceedings of the 50th Annual Meeting of the European Association for the Study of the Liver, Abstract O008, Vienna, Austria, April 2015.
  38. P. Kwo, E. Gane, C.-Y. Peng et al., “Efficacy and safety of grazoprevir/elbasvir ± RBV for 12 or 16 weeks in patients with HCV G1, G4, or G6 infection who previously failed peginterferon/RBV: C-EDGE treatment-experienced,” in Proceedings of the 50th Annual Meeting of the European Association for the Study of the Liver, Abstract P0886, Vienna, Austria, April 2015.
  39. X. Forns, S. C. Gordon, E. Zuckerman et al., “Grazoprevir and elbasvir plus ribavirin for chronic HCV genotype-1 infection after failure of combination therapy containing a direct-acting antiviral agent,” Journal of Hepatology, vol. 63, no. 3, pp. 564–572, 2015. View at Publisher · View at Google Scholar · View at Scopus
  40. M. Buti, S. C. Gordon, E. Zuckerman et al., “Grazoprevir, elbasvir, and ribavirin for chronic hepatitis c virus genotype 1 infection after failure of pegylated interferon and ribavirin with an earlier-generation protease inhibitor: final 24-week results from C-SALVAGE,” Clinical Infectious Diseases, vol. 62, no. 1, pp. 32–36, 2016. View at Publisher · View at Google Scholar
  41. L. Platt, P. Easterbrook, E. Gower et al., “Prevalence and burden of HCV co-infection in people living with HIV: a global systematic review and meta-analysis,” The Lancet Infectious Diseases, 2016. View at Publisher · View at Google Scholar
  42. T. Von Schoen-Angerer, J. Cohn, T. Swan, and P. Piot, “UNITAID can address HCV/HIV co-infection,” The Lancet, vol. 381, no. 9867, p. 628, 2013. View at Publisher · View at Google Scholar · View at Scopus
  43. J. Y. Chen, E. R. Feeney, and R. T. Chung, “HCV and HIV co-infection: mechanisms and management,” Nature Reviews Gastroenterology and Hepatology, vol. 11, no. 6, pp. 362–371, 2014. View at Publisher · View at Google Scholar · View at Scopus
  44. M. Sulkowski, C. Hezode, J. Gerstoft 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,” The Lancet, vol. 385, no. 9973, pp. 1087–1097, 2015. View at Publisher · View at Google Scholar · View at Scopus
  45. Clinical Pharmacology [database online], Gold Standard, Tampa, Fla, USA, 2016, http://www.clinicalpharmacology.com.
  46. B. Hajarizadeh, J. Grebely, and G. J. Dore, “Epidemiology and natural history of HCV infection,” Nature Reviews Gastroenterology and Hepatology, vol. 10, no. 9, pp. 553–562, 2013. View at Publisher · View at Google Scholar · View at Scopus
  47. G. Dore, F. Altice, A. H. Litwin et al., “C-EDGE CO-STAR: efficacy of grazoprevir and elbasvir in persons who inject drugs (PWID) receiving opioid agonist therapy,” in Proceedings of the Annual Meeting of the American Association for the Study of Liver Diseases, Abstract 40, San Francisco, Calif, USA, November 2015.