Hepatitis C (HCV)

Chronic hepatitis C is a persistent, potentially progressive inflammatory liver disease caused by chronic infection with the hepatitis C virus (HCV). Worldwide there are an estimated 130 to 170 million persons with chronic HCV infection. There are 7 major genotypes (strains) of HCV, which have differing geographic distributions. Globally, about 40-60% of patients are infected with HCV genotype 1, with the remaining patients infected with HCV genotypes 2 through 7.

HCV is a member of the Flaviviridae family, with 7 major genotypes and a large number of subtypes. HCV infection is a highly dynamic process, with a viral half-life of a few hours and an average daily production and clearance rate of ≥10¹² viral particles. The lack of a proof-reading function of the HCV RNA polymerase provides the basis for the genetic variability observed in cell culture and in the clinic. These findings provide a rationale for the development and implementation of multi-drug antiviral combination therapies.

Patients with advanced hepatitis C can develop potentially fatal liver failure or liver cancer, and hepatitis C is estimated to account for over 350,000 deaths per year worldwide (WHO estimate). The current standard-of-care treatment for hepatitis C in the United States, for patients with HCV genotype-1 infection, is combined administration of pegylated-interferon, ribavirin, and first-generation HCV protease inhibitors. This multi-drug treatment is characterized by incomplete efficacy for HCV genotype-1 patients, variations in efficacy according to patients’ underlying human genetic factors, no established efficacy for patients infected with other HCV genotypes, substantial tolerance issues, and dosing inconveniences. Thus, there is a continuing need for more consistently effective and better tolerated HCV inhibitors that can be orally administered in future combination therapies for hepatitis C patients worldwide, regardless of HCV genotype, patient genetic factors, or disease stage.

HCV Program >>