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 05 December 2016

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News

Treatment of HCV infection by targeting microRNA

This week's issue of the New England Journal of Medicine investigates the treatment of HCV infection by targeting microRNA.

News image

The stability and propagation of hepatitis C virus (HCV) is dependent on a functional interaction between the HCV genome and liver-expressed microRNA-122 (miR-122).

Miravirsen is a locked nucleic acid–modified DNA phosphorothioate antisense oligonucleotide that sequesters mature miR-122 in a highly stable heteroduplex, thereby inhibiting its function.
 
Dr Janssen and colleagues from Canada performed a phase 2a study at 7 international sites, the team evaluated the safety and efficacy of miravirsen in 36 patients with chronic HCV genotype 1 infection.

Miravirsen resulted in a dose-dependent reduction in HCV RNA levels
New England Journal of Medicine

The patients were randomly assigned to receive 5 weekly subcutaneous injections of miravirsen at doses of 3 mg, 5 mg, or 7 mg per kilogram of body weight or placebo over a 29-day period.

The patients were followed until 18 weeks after randomization.
 
Miravirsen resulted in a dose-dependent reduction in HCV RNA levels that endured beyond the end of active therapy.

In the miravirsen groups, the mean maximum reduction in HCV RNA level from baseline was 1.2 for patients receiving 3 mg per kilogram, 2.9 for those receiving 5 mg per kilogram, and 3.0 for those receiving 7 mg per kilogram, as compared with a reduction of 0.4 in the placebo group.

During 14 weeks of follow-up after treatment, HCV RNA was not detected in 1 patient in the 5-mg group, and in 4 patients in the 7-mg group.

The researchers observed no dose-limiting adverse events, and no escape mutations in the miR-122 binding sites of the HCV genome.
 
Dr Janssen's team concludes, "The use of miravirsen in patients with chronic HCV genotype 1 infection showed prolonged dose-dependent reductions in HCV RNA levels without evidence of viral resistance."

NEJM 2013; 368: 1685-1694
03 May 2013

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