University of Pennsylvania, Department of Gastroenterology Research , Philadelphia, PA 19104 , USA.
Chronic Hepatitis C virus (HCV) infection is a major pandemic. The current standard of care includes peginterferon and ribavirin plus one of two protease inhibitors, boceprevir and telaprevir, for Genotype 1 patients and peginterferon and ribavirin for all other genotypes. The treatment landscape is rapidly evolving as a number of direct-acting antivirals (DAA) are being developed in clinical trials.
Daclatasvir, formerly labeled BMS-790052, is a first-in-class HCV NS5A inhibitor that has been demonstrated in Phase I and II trials to have a very potent antiviral effect across all genotypes and to have a potent clinical efficacy in both treatment naive and experienced cohorts. This review covers the whole spectrum of development of daclatasvir from Phase I to III programs.
While daclatasvir has pangenotypic activity, it has a lower barrier to resistance in Genotype 1a but has been found to be very effective in Genotype 1b patients. However, Genotype 1a patients can be successfully treated with the addition of one or more DAAs alone or in combination with peginterferon and ribavirin. The future for daclatasvir and other DAAs is very encouraging in that all-oral therapies are likely to be effective and well-tolerated.