Sofosbuvir: Really Meets the Unmet Needs for Hepatitis C Treatment?

Abstract

Chronic hepatitis C remains a major public health concern with a prevalence of more than 1% worldwide. Of late, with the discovery of newer drugs, chronic HCV treatment has touched new dimensions. The treatment has progressed from Interferons to Pegylated interferon (Peg IFN) based therapy, with or without ribavirin to treatment with orally active Direct Acting Antivirals (DAA) with Peg IFN and ribavirin and eventually to various combinations of DAA, without IFN. Introduction of newer DAAs has transfigured the treatment of chronic HCV. Chronic HCV patients with advanced liver disease, psychiatric condition, anemia or autoimmune diseases, not eligible for Peg IFN based therapy have a ray of hope now. Amongst all DAAs, nucleoside inhibitors have been the most promising agent. Thus the present review focuses on Sofosbuvir, one of the most effective nucleoside inhibitors; in terms of potency, resistance profile, activity against all genotypes of HCV and adverse effects. FDA approved Sofobuvir for clinical use in 2013. Chemically, it is 2'-deoxy-2'-α-fluoro-β-Cmethyluridine- 5'-triphosphate; a phosphoramidate prodrug that is activated by enzyme present in human liver. It is a highly potent inhibitor of HCV NS5B polymerase. Efficacy of the Sofosbuvir has been established in various phase 2 and phase 3 clinical trials like PROTON, ELECTRON, FUSION, POSITRON etc. Sofosbuvir has a good safety profile with few mild to moderate adverse effects. Evidence reveals that sofosbuvir has substantial impact on the treatment of HCV.

Keywords: HCV; NS5B polymerase inhibitor; Sofosbuvir; chronic hepatitis C; direct acting antivirals; nucleoside inhibitors..