Boceprevir: a novel nonstructural 3 (NS3) protease inhibitor for the treatment of chronic hepatitis C infection

Chronic hepatitis C infection is a leading cause of morbidity and mortality worldwide, with hepatitis C related cirrhosis being the most common indication for transplant and a major cause for the increase in hepatocellular carcinoma worldwide. Treatment for hepatitis C has consisted of nonspecific immunomodulatory therapies that stimulate the immune system and inhibit hepatitis C replication. Pegylated (peg-) interferon and ribavirin have been the standard of care with an overall sustained response rate of 40-50% in patients with genotype 1 infection, and 80% in genotype 2 or 3. Recently, direct-acting antiviral agents, including boceprevir, have demonstrated improved sustained response rates in patients with genotype 1 infection when given in combination with interferon and ribavirin. Boceprevir is a structurally novel hepatitis C virus (HCV) nonstructural 3 (NS3) protease inhibitor that has demonstrated robust antiviral activity in HCV replicons. Clinically, in phase II and III trials, boceprevir 800 mg three times daily with peginterferon and ribavirin has led to improved sustained response rates in genotype 1 infection treatment-naive patients, relapsers, partial responders, and null responders. Phase II data have demonstrated that ribavirin is essential for optimal boceprevir response. Moreover, phase II data have suggested that a 4-week peginterferon or ribavirin lead-in strategy may reduce relapse rates and provide crucial on-treatment data for treatment response with boceprevir addition. Side effects of boceprevir when added to peginterferon and ribavirin are similar to peginterferon and ribavirin, though higher rates of anemia have been noted, with an incremental increase in erythropoietin use. The addition of boceprevir represents a major advance in patients with genotype 1 infection who are treatment naive.