The standard treatment for hepatitis C is typically a combination of an intravenous pegylated interferon and the nucleoside inhibitor antiviral agent ribavirin for a year. Side-effects generally make treatment an unpleasant experience, and with a cure rate of only around 50% of patients being cured, better treatments are much needed if the worst long-term effects of HCV infection – cirrhosis and liver cancer – are to be avoided.
Several add-on therapies have already been approved, notably Merck’s boceprevir and Vertex’s telaprevir, both of which are protease inhibitors that bind to the NS3/NS4a active site of the virus. Various other new agents are being developed, including Medivir and Janssen’s simeprevir. It is a potent inhibitor of HCV NS3/4A protease.1
Numerous trials have been carried out. In one Phase III study, 391 treatment-naïve patients with chronic genotype-1 HCV infection were given 150mg or placebo once a day in addition to standard peg-interferon and ribavirin therapy for 24 or 48 weeks, in a treatment guided regimen where therapy was stopped at the earlier point if there was early treatment success.2
Seventy-nine per cent of the simeprevir group achieved a rapid virologic response (RVR) and completed treatment after 24 weeks, compared with 13% of those given placebo. They were also less likely to experience on-treatment failure or relapse. Adverse event profiles were similar across all patients, although a slightly higher proportion of the simeprevir group developed rash or photosensitivity. The sustained virologic response (SVR) for simeprevir was 81%.
In another Phase III trial, 394 chronically genotype-1 HCV infected patients were again given 150mg simeprevir or placebo on top of standard therapy.3 Results were similar: there was an 80% SVR rate in the simeprevir group and a 50% SVR in the placebo group. The response was achieved faster in the simeprevir group again, with a RVR of 80% after simeprevir treatment, and just 12% for placebo. The most common adverse events were fatigue, pruritis and headache, with a similar incidence of anaemia and rash in both groups. In all, 85% of patients given simeprevir could shorten their duration of treatment to 24 weeks.
Fatigue is a real issue for HCV infected patients, particularly those undergoing standard therapy, and a further, Phase IIb, trial looked at the length of time patients reported fatigue.4 The treatment-naïve trial subjects (in this case, 386) were given standard therapy plus either 75mg or 150mg of simeprevir, or placebo. Again, therapy was continued for 24 or 48 weeks, depending on response. In the simeprevir treated group, patient reported fatigue scores were significantly lower than the placebo group at both weeks 36 and 48.
It is also undergoing trials in non-interferon-containing regimens that include other antiviral agents such as daclatasvir, and was approved in Japan in September for genotype-1 chronic hepatitis C virus infection.
References
1. T.I. Lin et al. Antimicrob. Ag. Chemother. 2009, 43, 1377
2. M. Manns et al. J. Hepatol. 2013, 58 (Suppl. 1), Abst. 1413
3. J. Jacobson et al. J. Hepatol. 2013, 58 (Suppl. 1), Abst. 1425
4. J. Scott et al. J. Hepatol. 2013, 58 (Suppl. 1), Abst. 902
