Hepatitis C - boceprevir
For the 50% of chronic hepatitis C patients who do not respond to the standard treatment of ribavirin plus interferon, treatment options are extremely limited. Boceprevir is being investigated in combination with peginterferon, and also the standard peginterferon/ribavirin therapy.
For the 50% of chronic hepatitis C patients who do not respond to the standard treatment of ribavirin plus interferon, treatment options are extremely limited. Boceprevir, developed by Schering-Plough, now part of Merck,1 is an orally available inhibitor of HCV NS3 protease, and is being investigated in combination with peginterferon, and also the standard peginterferon/ribavirin therapy.
Many studies have been carried out, including one in non-responders that showed some are able to achieve a sustained virological response (SVR) when 800mg of boceprevir is added to the standard therapy if there is a residual response to interferon.2
In a large multicentre standard therapy controlled Phase II trial, 595 treatment naïve patients with genotype 1 HCV infection were given one of three treatment regimens.3 Subjects were given pegintron and ribavirin for four weeks, and then between 800 and 1400mg of boceprevir was added to the combination for 24 or 44 weeks; all three drugs for the whole 28 or 48 weeks; or the combination with a lower dose of ribavirin for 48 weeks.
The rationale for the lead-in period in the first regimen was that it had been shown to reduce viral breakthrough. In this group, those given the new drug in the 48 week regimen achieved a 75% SVR rate, compared with 38% for standard therapy alone. In the shorter version of this regimen, 56% achieved SVR. Patients given this lead-in were more likely to achieve SVR. The low dose ribavirin group was associated with increased viral break-through during treatment, higher relapse rates at the end of treatment and a lower SVR, indicating strongly that standard dose ribavirin is still required.
In a retrospective analysis to determine the SVR in patients who had a null response to peginterferon and ribavirin after the four week lead in period, 38% achieved SVR by the end of the trial.4 Phase III trials are under way.
References:
1. S. Venkatraman et al. J. Med. Chem. 2006, 49, 6074
2. E. Schiff et al. Gastroenterol. 2008, 134 (4, Suppl. 1), Abst 162
3. P. Kwo et al. 44th Eur. Association Study Liver Ann. Meet. (Copenhagen, 22-26 April), 2009, Abst 4
4. P. Kwo et al. Amer. Assoc. Study Liver Dis. Ann. Meet. (Boston, Oct 30 - Nov 3), 2009, Abst. 62