Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Article
  • Published:

Emerging strategies for pegylated interferon combination therapy

Nature Clinical Practice Gastroenterology & Hepatology volume 4, pages S17–S21 (2007)Cite this article

Abstract

Several advances afford promise for improving the management of hepatitis C virus (HCV) infection. Current therapies primarily target the immune system; the now proven ability to culture the entire virus in vitro could ultimately facilitate the identification of therapies directly targeting viral replication. Several therapies are presently in development. Taribavirin hydrochloride (Viramidine®, Valeant Pharmaceutical International, Singapore), a ribavirin prodrug, has shown promise, although the rate of sustained virologic response with this agent has been disappointing. The next generation of antivirals will consist of protease and polymerase inhibitors, a number of which are undergoing investigation, initially as monotherapy and subsequently in combination with pegylated interferon and ribavirin. Challenges include the prevention of recurrent HCV infection in liver-transplant recipients and development of a safe and effective HCV vaccine.

Key Points

  • The ability to culture the entire hepatitis C virus (HCV) in vitro is likely to increase the rate of development of new antivirals, particularly polymerase and protease inhibitors

  • VX-950, a protease inhibitor, produces a rapid and dramatic decrease in levels of HCV RNA in a dose-related fashion

  • The addition of the protease inhibitor SCH-503034 to pegylated interferon produces a dose-dependent decrease in levels of HCV RNA beyond that seen with pegylated interferon alone in nonresponders to pegylated interferon plus ribavirin

  • Polymerase inhibitors are undergoing preclinical and clinical trials

  • Ongoing clinical trials of these agents should shed more light on their efficacy and safety in patients with HCV infection

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1: Incidence of anemia with increasing doses of taribavirin hydrochloride (Viramidine®, Valeant Pharmaceutical International, Singapore) versus ribavirin
Figure 2: Change in hepatitis C virus RNA level with the addition of SCH-503034 (Schering-Plough, Kenilworth, NJ) to pegylated interferon therapy
Figure 3: Change in hepatitis C virus RNA with valopicitabine (Idenix/Novartis International AG, Cambridge, MA/Basel, Switzerland) as monotherapy or in combination with pegylated interferon α-2b therapy

Similar content being viewed by others

References

  1. Zhong J et al. (2005) Robust hepatitis C virus infection in vitro. Proc Natl Acad Sci U S A 102: 9294–9299

    Article  CAS  Google Scholar 

  2. Wakita T et al. (2005) Production of infectious hepatitis C virus in tissue culture from a cloned viral genome. Nat Med 11: 791–796

    Article  CAS  Google Scholar 

  3. Lindenbach BD et al. (2005) Complete replication of hepatitis C virus in cell culture. Science 309: 623–626

    Article  CAS  Google Scholar 

  4. Gish RG et al. (2004) End-of-treatment (EOT) response in therapy-naïve patients treated for chronic hepatitis C with viramidine in combination with pegylated interferon alfa-2a. Hepatology 40 (Suppl 1): 519A

    Google Scholar 

  5. Benhamou Y et al. (2006) The safety and efficacy of Viramidine® plus pegylated interferon alfa-2b versus ribavirin plus pegylated interferon alfa-2b in therapy-naïve patients infected with HCV: phase 3 results [abstract #751]. Presented at the 41st Annual Meeting of the European Association for the Study of the Liver: 2006 April 26–30; Vienna, Austria

  6. Reesink HW et al. (2005) Initial results of a phase 1B, multiple dose study of VX-950, a hepatitis C virus protease inhibitor. Gastroenterology 128 (Suppl): A-697

    Google Scholar 

  7. Reesink HW et al. (2005) Final results of a phase 1B, multiple-dose study of VX-950, a hepatitis C virus protease inhibitor. Hepatology 42 (Suppl 1): 234A–235A

    Google Scholar 

  8. Vertex Pharmaceuticals Incorporated (2006) Vertex successfully completes key studies with VX-950 to prepare for next steps in clinical program [http://www.vpharm.com/Pressreleases2006/pr020706.html] (accessed July 7 2006)

  9. Lawitz EJ et al. (2006) 28 days of the hepatitis C protease C inhibitor VX-950, in combination with peg-interferon-alfa-2a and ribavirin, is well-tolerated and demonstrates robust antiviral effects [abstract #686f]. Gastroenterology 131: 950–951

    Article  Google Scholar 

  10. Zeuzem S et al. (2005) Anti-viral activity of SCH 503034, a HCV protease inhibitor, administered as monotherapy in hepatitis C genotype-1 (HCV-1) patients refractory to pegylated interferon (PEG-IFN-α). Hepatology 42: 233A

    Google Scholar 

  11. Malcolm BA (2005) Modeling of hepatitis C viral dynamics during combination therapy with peginterferon alfa-2B (peg-intron) and the NS3 protease inhibitor SCH 503034 [abstract #1266]. Presented at the Annual Meeting of the American Association for the Study of Liver Disease: 2005 November 11–15; San Francisco, CA

  12. Foy E et al. (2005) Control of antiviral defenses through hepatitis C virus disruption of retinoic acid-inducible gene-I signaling. Proc Natl Acad Sci USA 102: 2986–2991

    Article  CAS  Google Scholar 

  13. Kempf DJ et al. (2006) Pharmacokinetic boosting of VX-950, an inhibitor of HCV protease, by co-dosing with ritanovir [abstract #4]. Presented at the 41st Annual Meeting of the European Association for the Study of the Liver: April 26–30; Vienna, Austria

  14. Rodriguez-Torres M (2005) Valopicitabine (nm283) alone and in combination with peg-interferon in patients with genotype 1 chronic hepatitis C: preliminary results from an ongoing phase II, multicenter study. Gastroenterology 128 (Suppl): A-695

    Google Scholar 

  15. Tomei L et al. (2005) HCV antiviral resistance: the impact of in vitro studies on the development of antiviral agents targeting the viral NS5B polymerase. Antivir Chem Chemother 16: 225–245

    Article  CAS  Google Scholar 

  16. Viral Hepatitis Resource Center [http://www.cdc.gov/ncidod/diseases/hepatitis/resource/index.htm] (accessed October 2 2006)

Download references

Author information

Author notes

  1. University of Miami School of Medicine, 1500 NW 12 Avenue, Jackson Medical Tower E-1101, Miami, FL 33136, USA eschiff@med.miami.edu

Authors and Affiliations

  1. Chief of the Division of Hepatology, ER Schiff is the Leonard Miller Professor of Medicine, and Director of the Center for Liver Disease at the University of Miami School of Medicine, Miami, FL, USA.,

    Eugene R Schiff

Authors
  1. Eugene R Schiff
    View author publications

    You can also search for this author in PubMed Google Scholar

Ethics declarations

Competing interests

Eugene R Schiff acts as a consultant to Abbott, Achillion Pharmaceutical, Bayer, Bristol Myers Squibb, Cadence Pharmaceuticals, Gilead, GlobeImmune Inc., Idenix, Maxim, National Genetics Institute, Novartis, Ortho-Biotech, Pfizer, PowerMed Ltd., Prometheus, Roche Molecular, Sankyo Pharma Inc., Schering-Plough, and SciClone Pharmaceuticals. He has received grant support from Abbott, Bayer, Bristol Myers Squibb, Coley, Gilead, GlaxoSmithKline, Idenix, Ortho-Biotech, Prometheus, Roche Diagnostics, Roche Molecular, Roche Pharmaceutical, Schering-Plough, SciClone Pharmaceuticals, and Vertex Pharamceuticals. He also receives honoraria for speaking from Abbott, Bristol Myers Squibb, Giliead, GlaxoSmithKline, Idenix, Ortho-Biotech, and Schering-Plough.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Schiff, E. Emerging strategies for pegylated interferon combination therapy. Nat Rev Gastroenterol Hepatol 4 (Suppl 1), S17–S21 (2007). https://doi.org/10.1038/ncpgasthep0691

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1038/ncpgasthep0691

This article is cited by

Search

Advanced search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing