Format

Send to

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

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

Author information

1
Department of Gastroenterology and Hepatology, Academic Medical Center, Amsterdam, The Netherlands.
2
Department of Gastroenterology and Hepatology, Erasmus Medical Center, Rotterdam, The Netherlands.
3
PRA International, Zuidlaren, The Netherlands.
4
J.W. Goethe University Hospital, Frankfurt, Germany.
5
The Texas Liver Institute, University of Texas Health Science Center, San Antonio, TX, USA.
6
Fundacion de Investigacion, San Juan, Porto Rico.
7
Department of Internal Medicine, Derer's Hospital, University Hospital Bratislava, Slovakia.
8
Medical University of Warsaw, Warsaw Hospital for Infectious Diseases, Warsaw, Poland.
9
Santaris Pharma A/S, San Diego, USA.
10
Department of Gastroenterology and Hepatology, Erasmus Medical Center, Rotterdam, The Netherlands; Liver Clinic, Toronto Western & General Hospital, University Health Network, Toronto, Canada.
11
Department of Gastroenterology and Hepatology, Academic Medical Center, Amsterdam, The Netherlands. Electronic address: h.w.reesink@amc.uva.nl.

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

PMID:
25218783
DOI:
10.1016/j.antiviral.2014.08.015
[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for Elsevier Science
Loading ...
Support Center