Emerging therapeutic options for the management of hepatitis C infection

Abstract

Until recently the traditional treatment for hepatitis C infection included pegylated interferon and ribavirin combination therapy. The sustained virological response (SVR) seen with this combination is poor and requires lengthy treatment to achieve. Additionally, significant side effects and numerous contraindications prevented many patients from being successfully treated with this therapy. In 2011, two new protease inhibitors, telaprevir and boceprevir, were approved for use with pegylated interferon and ribavirin in the United States by the United States Food and Drug Administration. These agents have significantly improved SVR rates; however significant problems with toxicity remain including severe skin rash and neutropenia. There are a wide range of compounds in late stage development for the future treatment of hepatitis C that exploit many different mechanisms of viral inhibition. Some of these compounds include additional protease inhibitors, like telaprevir and boceprevir, as well as inhibitors of other nonstructural proteins in the viral genome such as NS5A and NS5B, and compounds that target host proteins within the virus. Some of these agents are being developed for oral administration once daily and various combinations are being assessed for use without the need for pegylated interferon and ribavirin. This paper reviews agents in late phase development that may be commercially available within 1-2 years.

Keywords: Hepatitis C; Pharmacotherapy; Interferon; Ribavirin; Protease inhibitors; Polymerase inhibitors; Cyclophilin inhibitors

Core tip: A plethora of new agents for the management of hepatitis C promising higher response rates and better tolerated side effect profiles is upon us. Many of these new drugs in development utilize novel pharmacologic mechanisms and may replace older more toxic therapies such as interferon and ribavirin. In addition, once daily dosing and shorter treatment durations should help improve adherence and optimize therapeutic outcomes for hepatitis C infection.