Efficacy and safety of new protease inhibitor faldaprevir in treatment of hepatitis C

The aim of review. To discuss potentials of application of new NS3/NS4 protease inhibitor faldaprevir at chronic hepatitis C with genotype 1 HCV, including patients without response to previous antiviral therapy, liver cirrhosis, and to estimate its antiviral activity in the range of treatment modes without interferon.

Key points. Significant progress was achieved in development of new modes of antiviral treatment of patients with the 1st HCV genotype due to introduction of the third agent possessing direct antiviral action. Faldaprevir (BI-201335) is NS3/4A protease inhibitor with long-term half-life period that allows once per day dosing. The combination of faldaprevir to interferon and ribavirin has essentially increased efficacy of treatment at previously untreated patients with hepatitis C genotype 1 (according to results of SILEN-C1 study, frequency of SVR achievement was 82% in group receiving faldaprevir in comparison to 56% of patients, who received placebo). Addition of faldaprevir to treatment mode has allowed to increase frequency of SVR (to 50%) in patients with unsuccessful course of standard antiviral therapy. Peak efficiency of triple mode with inclusion of faldaprevir was marked in patients with 1b genotype and «favorable» genotype Il28B СС (SVR up to 95%). In 88% of previously untreated patients it was possible to reduce treatment duration for triple algorithm (with faldaprevir application) to 12 wks with the subsequent transition to interferon and ribavirin for 12 wks (according to data of STARTVerso1 study). Faldaprevir has demonstrated equally good tolerability, high safety and antiviral activity in patients at different stages of fibrosis and liver cirrhosis in the range of interferon-free treatment modes.

Conclusion. Clinical investigations demonstrated that combination of faldaprevir with interferon and ribavirin essentially increases treatment response rate both in previously untreated patients with 1-st genotype, and in patients with unsuccessful experience of antiviral therapy; it allows to reduce treatment duration in certain groups of patients. The drug possesses high safety profile and good tolerability, including patients with liver cirrhosis spectrum of treatment modes without interferon.

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