Telaprevir: a new hope in the treatment of chronic hepatitis C?
More than 180 million people worldwide have chronic hepatitis C (CHC) virus infection, a major cause of liver cirrhosis and its life-threatening complications including liver failure, portal hypertension, and hepatocellular carcinoma. With the current standard of care of pegylated interferon-alpha and ribavirin (PEG-IFN-alpha/RBV), the chances of sustained viral clearance or "cure" are only 40%-50% for genotype 1 infection, which is the most common genotype in western populations. Consequently, there has been a drive to develop new agents specifically targeting essential components of the viral life cycle, such as the hepatitis C virus (HCV) NS3/4A serine protease. Perhaps the most advanced HCV protease inhibitor in clinical development is telaprevir, which has been shown to improve treatment outcomes when combined with PEG-IFN-alpha/RBV in genotype 1 infection, and is currently undergoing phase 3 study. In this review, we summarize the pharmacology, pharmacokinetics, and results of phase 1 and 2 clinical trials of telaprevir, and discuss the likely role of this agent in the future management of CHC.
Fowell
Andrew J
AJ
Southampton University Hospitals Trust, Southampton, UK. afowell@hotmail.com
Nash
Kathryn L
KL
D000998:Antiviral Agents / Q000627:therapeutic use; D002986:Clinical Trials as Topic; D004357:Drug Synergism; D020022:Genetic Predisposition to Disease; D016174:Hepacivirus / Q000187:drug effects* / Q000235:genetics; D019698:Hepatitis C, Chronic / Q000150:complications / Q000188:drug therapy* / Q000235:genetics / Q000503:physiopathology; D006801:Humans; D016898:Interferon-alpha / Q000627:therapeutic use; D008103:Liver Cirrhosis / Q000209:etiology; D009842:Oligopeptides / Q000494:pharmacology; D012254:Ribavirin / Q000627:therapeutic use; D015842:Serine Proteinase Inhibitors / Q000235:genetics / Q000627:therapeutic use; D016896:Treatment Outcome
D000998:Antiviral Agents; D016898:Interferon-alpha; D009842:Oligopeptides; D015842:Serine Proteinase Inhibitors; D012254:Ribavirin; C486464:telaprevir