Long-term safety and efficacy of microRNA-targeted therapy in chronic hepatitis C patients

Meike H. Van Der Ree, Adriaan J. Van Der Meer, Joep De Bruijne, Raoel Maan, Andre Van Vliet, Tania M. Welzel, Stefan Zeuzem, Eric J. Lawitz, Maribel Rodriguez-Torres, Viera Kupcova, Alcija Wiercinska-Drapalo, Michael R. Hodges, Harry L.A. Janssen, Hendrik W. Reesink

Research output: Contribution to journalArticle

109 Scopus citations

Abstract

Background and aims MicroRNA-122 (miR-122) is an important host factor for hepatitis C virus (HCV) and promotes HCV RNA accumulation. Decreased intra-hepatic levels of miR-122 were observed in patients with hepatocellular carcinoma, suggesting a potential role of miR-122 in the development of HCC. Miravirsen targets miR-122 and resulted in a dose dependent and prolonged decrease of HCV RNA levels in chronic hepatitis C patients. The aim of this study was to establish the sustained virological response rate to peginterferon (P) and ribavirin (R) following miravirsen dosing and to assess long-term safety in patients treated with miravirsen. Methods In this multicenter, retrospective follow-up study we included 36 treatment naïve patients with chronic hepatitis C genotype 1 who received five weekly subcutaneous injections with miravirsen or placebo over a 29-day period in a phase 2a study. Patients were offered PR therapy 3 weeks (3 mg/kg group) or 6 weeks (5 or 7 mg/kg group) after completion of miravirsen or placebo dosing. Results PR therapy was started in 14/36 patients of whom 12 had received miravirsen. SVR was achieved in 7/12 patients previously dosed with miravirsen. All patients dosed with 7 mg/kg miravirsen who were subsequently treated with PR achieved SVR. One patient had a prolonged undetectable HCV RNA period from week 14 to week 29 after baseline without subsequent antiviral therapy and relapsed thereafter. None of the patients treated with anti-miR-122 developed HCC or other liver-related complications. Conclusion No long-term safety issues were observed among 27 miravirsen-treated patients. Targeting miR-122 may be an effective and safe treatment strategy for HCV infection and should be investigated in larger clinical trials.

Original languageEnglish (US)
Pages (from-to)53-59
Number of pages7
JournalAntiviral Research
Volume111
DOIs
StatePublished - Nov 2014

Keywords

  • Anti-miRNA treatment
  • C virus
  • Hepatitis
  • MicroRNA's miR-122

ASJC Scopus subject areas

  • Pharmacology
  • Virology

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    Van Der Ree, M. H., Van Der Meer, A. J., De Bruijne, J., Maan, R., Van Vliet, A., Welzel, T. M., Zeuzem, S., Lawitz, E. J., Rodriguez-Torres, M., Kupcova, V., Wiercinska-Drapalo, A., Hodges, M. R., Janssen, H. L. A., & Reesink, H. W. (2014). Long-term safety and efficacy of microRNA-targeted therapy in chronic hepatitis C patients. Antiviral Research, 111, 53-59. https://doi.org/10.1016/j.antiviral.2014.08.015