Experimental treatments for hepatitis C virus and hepatitis C virus / HIV co-infection

A range of drugs targeting HCV or HCV-related liver damage are currently being studied in clinical trials.

The influenza drug amantadine (Lysovir / Symmetrel) in combination with interferon is being tested against HCV in treatment centres throughout the United Kingdom. In some past studies amantadine has led to lower ALT levels, but other trials found no benefit.

New types of interferon are under study for hepatitis C, including Albuferon (a long-acting form of interferon alfa bound to the blood protein albumin), interferon tau, and interferon lambda.¹

Two other forms, consensus interferon alfa (Infergen) and interferon gamma 1b (Actimmune), both produced by InterMune, are being studied as potential treatments for people who do not respond or who relapse after initial treatment.^{2 3 4}

Several other immune-modulating therapies are under study including etanercept (Enbrel), an agent that blocks tumor necrosis factor;⁵ Ceplene; thymosin (Zadaxin); and mycophenolate mofetil (CellCept).

HCV protease and integrase inhibitors are also currently being tested in trials. Boehringer Ingelheim has a serine-protease inhibitor called BILN-2061 in phase II trials,⁶ while Vertex is developing telaprevir in partnership with Tibotec. Results from a phase III study in monoinfected individuals with HCV genotype 1 infection showed an SVR of 80% when telaprevir was dosed in combination with pegylated interferon and ribavirin for 24 to 48 weeks (according to response during weeks 4-20). Telaprevir is expected to receive a US license for use in monoinfected individuals in mid-2011.^{7 8}

A study of Schering-Plough’s boceprevir, the first hepatitis C protease inhibitor to be trialled, found SVR rates of 82% in patients with genotype 1 who had an undetectable viral load by week four, and 79% by those who had not achieved one by week four but had by week 16. And a second boceprevir study found an SVR rate of 55% among patients who had previously failed to respond to pegylated interferon/ribavirin. In these studies, pegylated interferon/ribavirin is given for four weeks then boceprevir added for 24 weeks (in naïve patients) and 44 weeks (in previous non-responders). ^{9 10}

Small studies to date have shown no evidence that previous pegylated interferon-ribavirin therapy would affect susceptibility to HCV protease inhibitors.¹¹

Another Vertex drug, merimepodib (VX-497), works similarly to ribavirin, inhibiting inosine monophosphate dehydrogenase (IMPDH). Other experimental IMPDH inhibitors in clinical trials include levovirin and viramidine, a prodrug of ribavirin. Experimental nucleoside analogues include valopicitabine (NM-283) and isatoribine (ANA245).

Other hepatitis C therapies in the pipeline include internal ribosome entry site (IRES) inhibitors (e.g. ISIS 14803); polymerase inhibitors (e.g. JTK-003 and R1626); helicase inhibitors; budding inhibitors (e.g., UT-231B); caspase inhibitors (e.g., IDN-6556); monoclonal antibodies (e.g., HepeX-C, HuMax-HepC); ribozymes; antisense oligonucleotides; and small interfering RNA sequences (siRNAs).

Preventative and therapeutic vaccines for hepatitis C are also being developed. These are mostly in the early stages of development and are hampered by the difficulty of stimulating an immune response against all the many variant forms of HCV.[ref] One therapeutic vaccine in development, IC41, has produced a modest (-0.47 log) decline in HCV viral load, but one that has been sustained for up to 20 weeks thus far.¹²