Narlaprevir

Narlaprevir (trade name Arlansa, codenamed SCH 900518), is an inhibitor of NS3/4A serine protease, intended for the treatment of chronic hepatitis C caused by genotype 1 virus) in combination with other antiviral drugs. Narlaprevir (trade name Arlansa, codenamed SCH 900518), is an inhibitor of NS3/4A serine protease, intended for the treatment of chronic hepatitis C caused by genotype 1 virus) in combination with other antiviral drugs. Narlaprevir is the first Russian tableted medication for the treatment of chronic hepatitis C. Narlaprevir is an oral NS3 serine protease inhibitor of hepatitis C virus. It inhibits viral replication in infected host cells. The mechanism of inhibition involves reversible covalent binding of narlaprevir with NS3 protease active site via the ketoamide functional group. Narlaprevir does not bind to human proteases, with the exception of cathepsin B (69% inhibition). Overexpression of cathepsin B is associated with the development of malignancies. Treatment of chronic hepatitis C virus (HCV) infection genotype 1 in combination with ritonavir, pegylated interferon alfa and ribavirin, in patients older than 18 years with compensated liver disease who are treatment-naïve or have failed dual combination of pegylated interferon alfa and ribavirin. Narlaprevir cannot be used as a single agent. Narlaprevir has some contraindications. In particular: H. Reesink et al. (2009) demonstrated narlaprevir safety and antiviral activity both as a single agent and in dual combination with pegylated interferon alfa-2b. X. Tong et al. (2010) demonstrated narlaprevir activity against HCV mutations causing resistance to boceprevir and telaprevir. In the year 2016 a large-scale phase III multicenter PIONEER study was completed. Sustained virologic response (SVR) was 89% in treatment-naïve and 70% in treatment-experienced patients 24 weeks after the end of treatment in the narlaprevir group, whereas in the control group SVR was only 59.6% in treatment-naïve and 24.5% in treatment-experienced patients on dual therapy with pegylated interferon alfa and ribavirin. Adding narlaprevir to dual therapy with pegylated interferon alfa and ribavirin did not affect narlaprevir safety profile. A phase I study of narlaprevir pharmacokinetics in combination with ritonavir in patients with compensated cirrhosis was also completed (Liver Meeting AASLD, 13–17 February 2015, San Francisco, California, USA).