Attacking the Hepatitis C Virus with New Mechanisms of Action: Drugs in the Pipeline

Paul J Pockros, M.D.

A number of strategies for drug development have focused on the combination of antiviral therapy in the form of pegylated interferon with approaches to modulate and/or induce a cellular immune response [4]. These strategies have been based on the successful outcome of combination therapy of interferon or pegylated interferon with ribavirin, which has been the standard of care for treatment of hepatitis C in the US and the EU since 1998 [5-7]. Challenges facing our current treatment of HCV include lack of efficacy in patients with difficult-to-treat disease, such as patients with cirrhosis or infected with HCV genotype 1 (who represent a majority of US HCV infections), the toxicity of combination therapy, the expense and difficulty of therapy and the poor reception of these treatments by many patients. The development of new hepatitis C antiviral agents is critical to our management of this disease. A number of approaches are under investigation, including long-acting interferons; immunomodulators such as Interleukin-12, IL-10 and IL-2, histamine, thymosin alpha-1, IMPDH inhibitors, TNF antagonists, oral interferon like molecules, ribavirin and ribavirin analogues, and hepatoprotectants; antifibrotics; specific HCV-derived enzyme inhibitors, drugs that either block HCV antigen production from RNA or prevent normal processing of HCV proteins;