Gastroenterology
Volume 131, Issue 4 , Pages 997-1002 , October 2006

Rapid Decline of Viral RNA in Hepatitis C Patients Treated With VX-950: A Phase Ib, Placebo-Controlled, Randomized Study

  • Hendrik W. Reesink

      Affiliations

    • Department of Gastroenterology and Hepatology, Academic Medical Center, Amsterdam, The Netherlands
    • Corresponding Author InformationAddress requests for reprints to: Hendrik W. Reesink, MD, Department of Gastroenterology and Hepatology, Academic Medical Center, Meibergdreef 9, 1105AZ Amsterdam, The Netherlands. fax: (31) 20 566 9240.
    • ,
  • Stefan Zeuzem

      Affiliations

    • Saarland University Hospital, Homburg, Germany
    • ,
  • Christine J. Weegink

      Affiliations

    • Department of Gastroenterology and Hepatology, Academic Medical Center, Amsterdam, The Netherlands
    • ,
  • Nicole Forestier

      Affiliations

    • Department of Gastroenterology and Hepatology, Academic Medical Center, Amsterdam, The Netherlands
    • ,
  • Andre van Vliet

      Affiliations

    • Pharma Bio-Research, Zuidlaren, The Netherlands
    • ,
  • Jeroen van de Wetering de Rooij

      Affiliations

    • Pharma Bio-Research, Zuidlaren, The Netherlands
    • ,
  • Lindsay McNair

      Affiliations

    • Vertex Pharmaceuticals Incorporated, Cambridge, Massachusetts
    • ,
  • Susan Purdy

      Affiliations

    • Vertex Pharmaceuticals Incorporated, Cambridge, Massachusetts
    • ,
  • Robert Kauffman

      Affiliations

    • Vertex Pharmaceuticals Incorporated, Cambridge, Massachusetts
    • ,
  • John Alam

      Affiliations

    • Vertex Pharmaceuticals Incorporated, Cambridge, Massachusetts
    • ,
  • Peter L.M. Jansen

      Affiliations

    • Department of Gastroenterology and Hepatology, Academic Medical Center, Amsterdam, The Netherlands

Received 10 April 2006 ,Accepted 15 June 2006.

References 

  1. World Health Organization. Hepatitis C. Fact sheet No. 164. Revised October 2000. http://www.who.int/mediacentre/factsheets/fs164/en. Accessed August 27, 2005.
  2. Fried MW, Shiffman ML, Reddy KR, Smith C, Marinos G, Goncales FL, et al. Peginterferon alfa-2a plus ribavirin for chronic hepatitis C virus infection. N Engl J Med. 2002;347:975–982
  3. Manns MP, McHutchison JG, Gordon SC, Rustgi VK, Shiffman M, Reindollar R, et al. Peginterferon alfa-2b plus ribavirin compared with interferon alfa-2b plus ribavirin for initial treatment of chronic hepatitis C: a randomised trial. Lancet. 2001;358:958–965
  4. Pawlotsky JM, McHutchison JG, Hepatitis C. Development of new drugs and clinical trials: promises and pitfalls. Hepatology. 2004;39:554–567
  5. Hinrichsen H, Benhamou Y, Wedemeyer H, Reiser M, Sentjens RE, Calleja JL, et al. Short-term antiviral efficacy of BILN 2061, a hepatitis C virus serine protease inhibitor, in hepatitis C genotype 1 patients. Gastroenterology. 2004;127:1347–1355
  6. Reiser M, Hinrichsen H, Benhamou Y, Reesink HW, Wedemeyer H, Avendano C, et al. Antiviral efficacy of NS3-serine protease inhibitor BILN-2061 in patients with chronic genotype 2 and 3 hepatitis C. Hepatology. 2005;41:832–835
  7. Lamarre D, Anderson PC, Bailey M, Beaulieu P, Bolger G, Bonneau P, et al. An NS3 protease inhibitor with antiviral effects in humans infected with hepatitis C virus. Nature. 2003;426:186–189
  8. Lin C, Lin K, Luong YP, Rao BG, Wei YY, Brennan DL, et al. In vitro resistance studies of hepatitis C serine protease inhibitors, VX-950 and BILN 2061: structural analysis indicates different resistance mechanisms. J Biol Chem. 2004;279:17508–17514
  9. Hadziyannis SJ, Sette H, Morgan TR, Balan V, Diago M, Marcellin P, et al. Peginterferon-α2a and ribavirin combination therapy in chronic hepatitis C: a randomized study of treatment duration and ribavirin dose. Ann Intern Med. 2004;140:346–355
  10. Tong X, Guo Z, Wright-Minogue J, Xia E, Prongay A, Madison V, et al. Impact of naturally occurring variants of HCV protease on the binding of different classes of protease inhibitors. Biochemistry. 2006;45:1353–1361
  11. Sarrazin C, Kieffer T, Bartels D, Hanzelka B, Muh U, Welker M, et al. Characterization of viral variants in the HCV NS3 protease domain of genotype 1 patients that are selected during 14 days of dosing with VX-950. Hepatology. 2005;42(Suppl 1):537A
  12. Lin K, Kwong AD, Lin C. Combination of a hepatitis C virus NS3·4A protease inhibitor with IFN-α synergistically inhibits viral RNA replication and facilitates viral RNA clearance in replicon cells. Antimicrob Agents Chemother. 2004;40:4784–4792
  13. Lin C, Gates CA, Rao BG, Brennan DL, Fulghum JR, Luong YP, et al. In vitro studies of cross-resistance mutations against two hepatitis C virus serine protease inhibitors, VX-950 and BILN 2061. J Biol Chem. 2005;280:36784–36791

 Supported by Vertex Pharmaceuticals Incorporated.

PII: S0016-5085(06)01539-3

doi: 10.1053/j.gastro.2006.07.013

Gastroenterology
Volume 131, Issue 4 , Pages 997-1002 , October 2006

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