Abstract
Chronic hepatitis C affects 130,000,000 people worldwide. Hepatitis C virus (HCV) is a single-strand RNA virus responsible for most cases of chronic hepatitis, liver cirrhosis and hepatocellular carcinoma (HCC) in the Western world. The gold standard for the treatment of chronic hepatitis C (combination of pegylated-interferon α and ribavirin) results in a sustained virological response (namely, clearance of serum HCV RNA 6 months after therapy withdrawal) in only about half treated patients. Therefore, there is a race to develop new drugs for the treatment of HCV infection. One of the most promising approaches is to use protease inhibitors, i.e. drugs inhibiting NS3/NS4A HCV protease, which plays a crucial role in the viral life cycle. Telaprevir (VX-950) is the protease inhibitor in the most advanced phase of clinical testing. Telaprevir is orally available and when used in monotherapy it induced a median decline of 4 logs of HCV RNA after two weeks of therapy. However, mutants with a lower sensitivity to telaprevir have been demonstrated in a high proportion of patients within 14 days of monotherapy. The drug has been used in clinical trials in combination with pegylatedinterferon and ribavirin. This triple combination resulted in a higher rate of SVR but also in a higher rate of side effects (rash, gastrointestinal disorders, and anemia) than standard treatment. This review focuses on the mechanism of action, pharmacokinetics, clinical efficacy, and tolerability of telaprevir, and on possible use of this drug in combination with other drugs for the treatment of HCV infection.
Keywords: Telaprevir, HCV, PEG-IFN, ribavirin, SVR, resistance, clinical trial, combination therapy
Current Medicinal Chemistry
Title: Telaprevir: A Promising Protease Inhibitor for the Treatment of Hepatitis C Virus Infection
Volume: 16 Issue: 9
Author(s): I. Gentile, C. Viola, F. Borgia, G. Castaldo and G. Borgia
Affiliation:
Keywords: Telaprevir, HCV, PEG-IFN, ribavirin, SVR, resistance, clinical trial, combination therapy
Abstract: Chronic hepatitis C affects 130,000,000 people worldwide. Hepatitis C virus (HCV) is a single-strand RNA virus responsible for most cases of chronic hepatitis, liver cirrhosis and hepatocellular carcinoma (HCC) in the Western world. The gold standard for the treatment of chronic hepatitis C (combination of pegylated-interferon α and ribavirin) results in a sustained virological response (namely, clearance of serum HCV RNA 6 months after therapy withdrawal) in only about half treated patients. Therefore, there is a race to develop new drugs for the treatment of HCV infection. One of the most promising approaches is to use protease inhibitors, i.e. drugs inhibiting NS3/NS4A HCV protease, which plays a crucial role in the viral life cycle. Telaprevir (VX-950) is the protease inhibitor in the most advanced phase of clinical testing. Telaprevir is orally available and when used in monotherapy it induced a median decline of 4 logs of HCV RNA after two weeks of therapy. However, mutants with a lower sensitivity to telaprevir have been demonstrated in a high proportion of patients within 14 days of monotherapy. The drug has been used in clinical trials in combination with pegylatedinterferon and ribavirin. This triple combination resulted in a higher rate of SVR but also in a higher rate of side effects (rash, gastrointestinal disorders, and anemia) than standard treatment. This review focuses on the mechanism of action, pharmacokinetics, clinical efficacy, and tolerability of telaprevir, and on possible use of this drug in combination with other drugs for the treatment of HCV infection.
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Gentile I., Viola C., Borgia F., Castaldo G. and Borgia G., Telaprevir: A Promising Protease Inhibitor for the Treatment of Hepatitis C Virus Infection, Current Medicinal Chemistry 2009; 16 (9) . https://dx.doi.org/10.2174/092986709787581789
DOI https://dx.doi.org/10.2174/092986709787581789 |
Print ISSN 0929-8673 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-533X |
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