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

Antiviral Res. 2014 Nov;111:53-9. doi: 10.1016/j.antiviral.2014.08.015. Epub 2014 Sep 8.

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 3weeks (3mg/kg group) or 6weeks (5 or 7mg/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 7mg/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.

Keywords: Anti-miRNA treatment; Hepatitis C virus; MicroRNA’s; miR-122.

Publication types

  • Clinical Trial, Phase II
  • Multicenter Study
  • Randomized Controlled Trial

MeSH terms

  • Adult
  • Aged
  • Antiviral Agents / administration & dosage*
  • Antiviral Agents / adverse effects
  • Female
  • Follow-Up Studies
  • Hepacivirus / drug effects*
  • Hepacivirus / genetics
  • Hepacivirus / physiology
  • Hepatitis C, Chronic / drug therapy*
  • Hepatitis C, Chronic / genetics*
  • Hepatitis C, Chronic / metabolism
  • Hepatitis C, Chronic / virology
  • Humans
  • Male
  • MicroRNAs / adverse effects
  • MicroRNAs / genetics
  • MicroRNAs / metabolism
  • MicroRNAs / therapeutic use*
  • Middle Aged
  • Oligonucleotides / administration & dosage*
  • Retrospective Studies
  • Time Factors
  • Treatment Outcome
  • Virus Replication / drug effects

Substances

  • Antiviral Agents
  • MIRN122 microRNA, human
  • MicroRNAs
  • Oligonucleotides
  • miravirsen