The combination of MK-5172, peginterferon, and ribavirin is effective in treatment-naive patients with hepatitis c virus genotype 1 infection without cirrhosis

Michael P. Manns, John M. Vierling, Bruce R. Bacon, Savino Bruno, Oren Shibolet, Yaacov Baruch, Patrick Marcellin, Luzelena Caro, Anita Y M Howe, Christine Fandozzi, Jacqueline Gress, Christopher L. Gilbert, Peter M. Shaw, Michael P. Cooreman, Michael N. Robertson, Peggy Hwang, Frank J. Dutko, Janice Wahl, Niloufar Mobashery

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Abstract

Background & Aims MK-5172 is an inhibitor of the hepatitis C virus (HCV) nonstructural protein 3/4A protease; MK-5172 is taken once daily and has a higher potency and barrier to resistance than licensed protease inhibitors. We investigated the efficacy and tolerability of MK-5172 with peginterferon and ribavirin (PR) in treatment-naive patients with chronic HCV genotype 1 infection without cirrhosis. Methods We performed a multicenter, double-blind, randomized, active-controlled, dose-ranging, response-guided therapy study. A total of 332 patients received MK-5172 (100, 200, 400, or 800 mg) once daily for 12 weeks in combination with PR. Patients in the MK-5172 groups received PR for an additional 12 or 36 weeks, based on response at week 4. Patients in the control group (n = 66) received a combination of boceprevir and PR, dosed in accordance with boceprevir's US product circular. Results At 24 weeks after the end of therapy, sustained virologic responses were achieved in 89%, 93%, 91%, and 86% of the patients in the groups given the combination of PR and MK-5172 (100, 200, 400, or 800 mg), respectively, vs 61% of controls. In the MK-5172 group receiving 100 mg, 91% of patients had undetectable levels of HCV RNA at week 4 and qualified for the short duration of therapy. The combination of MK-5172 and PR generally was well tolerated. Transient increases in transaminase levels were noted in the MK-5172 groups given 400 and 800 mg, at higher frequencies than in the MK-5172 groups given 100 or 200 mg, or control groups. Conclusions Once-daily MK-5172 (100 mg) with PR for 24 or 48 weeks was highly effective and well tolerated among treatment-naive patients with HCV genotype 1 infection without cirrhosis. Studies are underway to evaluate interferon-free MK-5172-based regimens. ClinicalTrials.gov number: NCT01353911.

Original languageEnglish
JournalGastroenterology
Volume147
Issue number2
DOIs
Publication statusPublished - 2014

Keywords

  • Chronic HCV
  • Protease Inhibitor
  • Response-Guided Therapy
  • Sustained Virologic Response

ASJC Scopus subject areas

  • Gastroenterology

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    Manns, M. P., Vierling, J. M., Bacon, B. R., Bruno, S., Shibolet, O., Baruch, Y., Marcellin, P., Caro, L., Howe, A. Y. M., Fandozzi, C., Gress, J., Gilbert, C. L., Shaw, P. M., Cooreman, M. P., Robertson, M. N., Hwang, P., Dutko, F. J., Wahl, J., & Mobashery, N. (2014). The combination of MK-5172, peginterferon, and ribavirin is effective in treatment-naive patients with hepatitis c virus genotype 1 infection without cirrhosis. Gastroenterology, 147(2). https://doi.org/10.1053/j.gastro.2014.04.006