Aliment Pharmacol Ther 2010 Jul 31;32(1):14-28. Epub 2010 Mar 31.
Department of Medicine, Johann Wolfgang Goethe University, Frankfurt am Main, Germany.
Background: Novel, directly acting anti-viral agents, also named 'specifically targeted anti-viral therapy for hepatitis C' (STAT-C) compounds, are currently under development.
Aim: To review the potential of STAT-C agents which are currently under clinical development, with a focus on agents that target HCV proteins.
Methods: Studies evaluating STAT-C compounds were identified by systematic literature search using PubMed as well as databases of abstracts presented in English at recent liver and gastroenterology congresses.
Results: Numerous directly-acting anti-viral agents are currently under clinical phase I-III evaluation. Final results of phase II clinical trials evaluating the most advanced compounds telaprevir and boceprevir indicate that the addition of these NS3/4A protease inhibitors to pegylated interferon-alfa and ribavirin strongly improves the chance to achieve a SVR in treatment-naive HCV genotype 1 patient as well as in prior nonresponders and relapsers to standard therapy. Monotherapy with directly acting anti-virals is not suitable. NS5B polymerase inhibitors in general have a lower anti-viral efficacy than protease inhibitors.
Conclusions: STAT-C compounds in addition to pegylated interferon-alfa and ribavirin can improve SVR rates at least in HCV genotype 1 patients. Future research needs to evaluate whether a SVR can be achieved by combination therapies of STAT-C compounds in interferon-free regimens.