Protease inhibitors: Silver bullets for chronic hepatitis C infection?
ABSTRACTRecent trials evaluated the safety and efficacy of two protease inhibitors, boceprevir (Victrelis) and telaprevir (Incivek), added to standard care with pegylated interferon and ribavirin, in patients with chronic hepatitis C virus (HCV) infection. These drugs open the door for triple therapy and other new therapies involving combinations of other direct-acting antiviral agents to become the new standard of care for this population.
KEY POINTS
- Standard care with the combination of pegylated interferon and ribavirin produces a sustained virologic response in about 40% of patients infected with HCV genotype 1, the most prevalent genotype in North America.
- New phase 3 trials showed that the addition of an oral protease inhibitor (boceprevir or telaprevir) increased the sustained virologic response rates to 70% in patients infected with HCV genotype 1.
- Boceprevir and telaprevir must be used in combination with pegylated interferon and ribavirin; they should not be used as monotherapy because of concern about the development of drug-resistant mutations.
- The main side effects of boceprevir were anemia and dysgeusia. Adverse events associated with telaprevir included rash, pruritus, anemia, and diarrhea.
FUTURE PERSPECTIVES
With the introduction of the first direct-acting antiviral medications for HCV (boceprevir and telaprevir), 2011 will be marked as the year that changed hepatitis C treatment for the better. Triple therapy with pegylated interferon, ribavirin, and either boceprevir or telaprevir has the potential for increasing the rate of sustained virologic response to around 70% in previously untreated patients and 65% in previously treated patients who are infected with HCV genotype 1. The IL28B polymorphisms appear to play a role in the rate of sustained virologic response achieved with triple therapy, with preliminary data showing a better response rate in patients who have the CC genotype.17
These drugs will add up to $50,000 to the cost of treating hepatitis C virus infection, depending on the drug used and the length of treatment. However, they may be well worth it if they prevent liver failure and the need for transplantation.
Many questions remain, such as how to use these new regimens to treat special patient populations—for example, those with a recurrence of HCV infection after liver transplantation, those co-infected with HCV and human immunodeficiency virus, and those infected with HCV genotypes other than genotype 1.
Other direct-acting antiviral agents that specifically target the replication cycle of HCV are currently in clinical development. In fact, the future has already started with the release of the Interferon-Free Regimen for the Management of HCV (INFORM-1) study results.30 This was the first trial to evaluate an interferon-free regimen for patients with chronic HCV infection using two direct-acting antiviral drugs (the protease inhibitor danoprevir and the polymerase inhibitor RG7128), with promising results.
