Simeprevir Works in Treatment-Experienced Patients with HCV Infection

Atif Zaman, MD, MPH

Triple therapy with simeprevir was superior to peginterferon and ribavirin alone in a phase IIb study of patients with genotype 1 infection who previously failed treatment.

Simeprevir, a next-generation protease inhibitor, in combination with peginterferon and ribavirin, was recently approved by the FDA for the treatment of genotype 1 hepatitis C virus (HCV) infection in treatment-naive patients. This regimen is as effective as the previous-generation protease inhibitor–based regimen with telaprevir or boceprevir in this population, but with a lower pill burden and fewer adverse effects. Now, investigators have examined its efficacy and safety in similar patients who failed previous treatment with peginterferon and ribavirin.

In a phase IIb, double-blind, randomized trial, 396 patients received simeprevir once daily (100 or 150 mg) for 12, 24, or 48 weeks plus peginterferon (180 µg weekly) and ribavirin (1000–1200 mg daily) for 48 weeks, and 66 received placebo plus peginterferon and ribavirin for 48 weeks. The primary endpoint was sustained virologic response (SVR) at 24 weeks posttreatment. Results included:

• Higher SVR rates in the simeprevir groups than in the placebo group, both overall (61%–80% vs. 23%; P<0.001) and when stratified by prior response status
• Higher SVR with 150 mg of simeprevir versus placebo in patients with cirrhosis (62% vs. 0%)
• Similar rates of adverse events between simeprevir and placebo recipients, with respective discontinuation rates of 8.8% and 4.5%

Despite inadequate power to detect differences between subgroups, among patients with prior null or partial response, the authors noted:

• No consistent increase in SVR rates by extending simeprevir treatment beyond 12 weeks
• Higher SVRs for genotype-1 subtype 1b versus 1a with 150 mg of simeprevir

Citation(s):

Zeuzem S et al. Simeprevir increases rate of sustained virologic response among treatment-experienced patients with HCV genotype-1 infection: A phase IIb trial. Gastroenterology 2013 Nov 4; [e-pub ahead of print].