Interferon-free combinations with MK-5172 and MK-8742 with or without ribavirin

Another interferon-free combination being tested in hepatitis C virus (HCV) genotype 1 patients is the combination protease inhibitor MK-5172 (Merck), the NS5A inhibitor MK-8742, with or without ribavirin. These experimental drugs have broad activity against multiple HCV genotypes and less susceptibility to HCV resistance. Early results from trials conducted in people who are treatment-naive have shown good efficacy across both subtypes. The combination of MK-5172 and MK-8742 (without ribavirin) has been shown to be effective in people with subtype 1b.1

C-WORTHY

The efficacy and safety of MK-5172 and MK-8742 with or without ribavirin is currently being evaluated in the C-WORTHY trial. The study is being conducted in 65 treatment-naive people with HCV genotype 1 infection without cirrhosis, who were randomly assigned to MK-5172 (100 mg daily) and to two different doses of MK-8742 with or without ribavirin for 12 weeks. Sustained virologic response (SVR) rates at 12 weeks after treatment range from 96% to 100%. Inclusion of ribavirin appears to have no effect on the likelihood of achieving SVR. Nor does subtype (1a versus 1b) or the presence of the IL-28 polymorphism.2

C-SPIRIT

MK-5172 was also evaluated in combination with ribavirin alone for 12 or 24 weeks in C-SPIRIT, a study that was conducted in 26 treatment-naive people with HCV genotype 1 who had the IL-28 CC polymorphism, which predicts stronger virologic response. Interim results from the study show 24 participants achieved undetectable levels of HCV during treatment.3

Safety and side effects

In C-WORTHY, the combination of MK-5172 and MK-8742 with or without ribavirin was well-tolerated, with the most common side effects including fatigue, headache, and nausea. Anemia appeared more frequently in participants who received the combination with ribavirin. The majority of participants in C-WORTHY had elevated liver enzyme levels (indicating impaired liver function) at the beginning of the study. These normalized during treatment in all but one person. Similarly, in C-SPIRIT, which evaluated MK-5172 in combination with ribavirin, all participants had elevated liver enzymes at the beginning of the study and in all cases these elevations normalized during treatment.2

Written by: Jonathan Simmons | Last reviewed: March 2015.
View References
  1. Tai AW, Chung RT. Investigational therapies for hepatitis C virus infection. Uptodate. Di Bisceglie AM, Bloom A, eds. Accessed at: www.uptodate.com. 2014.
  2. Gentile I, Coppola N, Buonomo AR, Zappulo E, Borgia G. Investigational nucleoside and nucleotide polymerase inhibitors and their use in treating hepatitis C virus. Expert Opin Investig Drugs 2014;21:1-13.
  3. Gane EJ, Ben Ari Z, Mollison L, et al. Efficacy and safety of an interferon-free regimen of MK-5172 + ribavirin for 12 weeks or 24 weeks in treatment naive, non-cirrhotic subjects with HCV GT1 infection: the C-SPIRIT study. Hepatology 2013;58:748-9.