Boceprevir versus telaprevir: A new era of directly acting antiviral therapy

Boceprevir (BOC or B) and telaprevir (TVR or T), two newly approved NS3/4A protease inhibitors, have revolutionized hepatitis C therapy for genotype 1 since their availability in 2011. The new regimens are highly effective in treatment naive and treatment experienced patients. They are administered three times daily, and have an extensive list of drug-drug interactions that require vigilance with drug co-administration. The phase 3 clinical trials that led to the drugs' approval are reviewed in detail with regard to the clinical trial design, efficacy and safety data. Both drugs utilize response guided therapy (RGT) based upon rapid virological response (RVR) and extended rapid virological response, (eRVR) and depend upon defined stopping rules to minimize the risk of resistance development and prolonged treatment with unavoidable treatment futility. Although both drugs depend upon a framework of pegylated IFN alfa (PEG) and ribavirin (RBV), with the expected adverse events, telaprevir adds an additional risk of rash, anorectal symptoms and worsened anemia. Boceprevir is associated with worsened anemia and dysgeusia. Although these two medical regimens are compared and contrasted in this paper, it must be recognized that comparisons are limited because there have been no direct, head-to-head comparison studies. The hope that the next generation of direct acting anti-viral agents (DAAs) will afford the development of safe and effective therapy for HCV, including all genotypes, fuels ongoing research development of HCV therapy.