Daclatasvir, an efficient inhibitor of the hepatitis C virus replication complex protein NS5A: review of virologic data, treatment rationale and clinical trials

摘要

The treatment of hepatitis C virus (HCV) infection with pegylated interferon a (PEG-a) and ribavirin (RBV) leads to a sustained virologic response in approximately 50% of patients with HCV genotype 1. A better understanding of the HCV life-cycle has resulted in the development of several potential direct-acting antiviral drugs (DAAs), targeting viral proteins (NS3/4A protease inhibitors, NS5B polymerase inhibitors, or NS5A replication complex inhibitors). This review summarizes the clinical data for daclatasvir (DCV; BMS-790052), the first NS5A replication complex inhibitor to enter clinical development, with potent activity, broad genotypic coverage in vitro, and a pharmacokinetic profile supportive of once-daily dosing. DCV, either in combination with PEG-a or in interferon-free regimens with other DAAs, has demonstrated a high level of antiviral efficacy and a generally well-tolerated safety profile in treatment-naive patients, and in prior non-responders to PEG-a/RBV. DCV is likely to become a key component of new oral combinations of DAAs for chronic HCV in treatment-naive or -experienced patients.