HCV has proteins that are essential in order for infected liver cells to make new copies of this virus. Newer HCV drugs are being developed that interfere with the HCV proteins NS3/4A; such drugs are called protease inhibitors. The drugs boceprevir and telaprevir are examples of currently licensed protease inhibitors for HCV treatment.
Drugs that interfere with another protein called NS5B are called polymerase inhibitors. There are two groups of these drugs -- nucleoside and non-nucleoside (non-nuke) inhibitors. In general, nucleosides that attack NS5B tend to have greater anti-HCV activity against several HCV genotypes. HCV exposed to nukes is less likely to develop resistance than when treated with non-nukes.
There are many drugs in development for HCV treatment. Below are a few.
This drug impairs the activity of the HCV proteins NS3/4A and is classed as a protease inhibitor. It has at least similar anti-HCV activity as boceprevir or telaprevir when used as part of combination therapy. Simeprevir is taken at a dose of 150 mg once daily. Common side effects include nausea, fatigue and flu-like symptoms. A phase III trial of simeprevir is underway. More information on simeprevir appears later in this issue of TreatmentUpdate.
This protease inhibitor interferes with the HCV protein NS3. It is taken twice daily and has been tested with another anti-HCV agent called daclatasvir. In such cases, dual therapy has cured some cases of HCV infection. More information about this drug appears later in this issue of TreatmentUpdate.
This drug is a protease inhibitor and attacks the HCV NS3 protein. BI 201335 is given once daily and is currently in phase III clinical trials where it is being taken in combination with peginterferon-alpha and ribavirin. In phase II clinical trials, cure rates with BI 201335-based therapy ranged between 73% and 87%. Side effects associated with this drug include temporary yellowing of the skin, rash, dry skin and sensitivity to sunlight. Also reported were nausea, vomiting and diarrhea.
This drug attacks the HCV protein NS5A. A combination of daclatasvir and asunaprevir, with or without peginterferon and ribavirin, has been tested in participants who had previously not responded to dual therapy with peginterferon-alpha and ribavirin. Quadruple therapy resulted in curing 90% of participants after 24 weeks. Double therapy with daclatasvir and asunaprevir resulted in a cure rate of 36%, suggesting that a subset of patients can be successfully treated with an interferon-free regimen.
This is a nucleoside NS5B polymerase inhibitor (formerly called PSI-7977). Preliminary clinical trials have found that GS-7977 has powerful anti-HCV activity against genotype 1 strains. When GS-7977 was used together with peginterferon-alpha and ribavirin in HCV gentotype 1 volunteers who had never previously received therapy, large decreases in HCV viral load occurred in as little as three days. When GS-7977 is used as part of triple therapy with interferon and ribavirin it appears to be effective against genotypes 2 and 3. Side effects associated with GS-7977 are not yet clear. Many clinical trials with this drug are planned or underway, some of which do not include using interferon. The best combinations of drugs to use with GS-7977 are not yet clear.
This drug is a non-nucleoside inhibitor of the HCV NS5B polymerase and has potent activity against the virus. Details about the use of this drug appear later in this issue of TreatmentUpdate.
This drug is a non-nuke that interferes with NS5B and has activity against HCV genotypes 1a and 1b. Side effects can include fatigue, mild nausea and diarrhea. A clinical trial of VCH-222 and telaprevir and ribavirin is planned.
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