Patients who received vaniprevir achieved higher rapid virologic response rates than those who received placebo.
Adding telaprevir and boceprevir to standard peginterferon and ribavirin therapy has been shown to significantly improve virologic response rates for patients with genotype 1 hepatitis C virus (HCV) infection (JW Gastroenterol Jul 1 2011 and JW Gastroenterol Mar 30 2011). However, these first-generation HCV nonstructured protein (NS)3/4A protease inhibitors require a complex administration schedule and are associated with additional adverse effects.
To evaluate the efficacy and safety of vaniprevir (MK-7009) — a macrocyclic next-generation HCV NS3/4A protease inhibitor that is administered once or twice daily — investigators conducted an industry-funded, phase II, multicenter, randomized, double-blind, placebo-controlled, dose-ranging study involving 94 treatment-naive adults with chronic HCV genotype 1 infection. Patients were assigned to vaniprevir (300 mg twice daily, 600 mg twice daily, 600 mg daily, or 800 mg daily) or matched placebo in combination with peginterferon (180 μg weekly) and ribavirin (1000–1200 mg daily) for 4 weeks. Thereafter, all patients continued peginterferon and ribavirin for 44 weeks. The primary endpoint was rapid virologic response (RVR); exploratory endpoints included sustained virologic response (SVR).
All 94 patients completed the 4-week triple-dosing regimen. Of these, 78 completed 48 weeks of peginterferon and ribavirin treatment, and 84 completed a 6-month post-therapy follow-up. The rate of viral decline by week 4 was at least 3log10 IU/mL greater in the vaniprevir groups versus the placebo group. Rates of RVR were significantly higher in all vaniprevir groups versus the placebo group (68.8%–83.3% vs. 5.6%; P<0.001). SVR rates were nonsignificantly higher in the vaniprevir groups than the placebo group (61.1%–84.2% and 63.2%, respectively), likely due to the small sample size. Safety profiles were similar between the vaniprevir and placebo groups, except vomiting occurred more often in the vaniprevir groups. HCV resistance variants were noted in three patients receiving vaniprevir.
Comment: This phase II study of vaniprevir shows early promise for a next-generation protease inhibitor–based triple therapy that is easy to administer in a daily or twice-daily dosing schedule. Subsequent vaniprevir studies are needed to identify the optimal dose and duration of therapy to maximize SVR and maintain an excellent safety profile.
Published in Journal Watch Gastroenterology September 28, 2012
Manns MP et al. Vaniprevir with pegylated interferon alpha-2a and ribavirin in treatment-naïve patients with chronic hepatitis C: A randomized phase II study. Hepatology 2012 Sep; 56:884. (http://dx.doi.org/10.1002/hep.25743)
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