microRNA inhibitor shows promise in the treatment of Hepatitis C

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1. Miravirsen, an antisense inhibitor of a microRNA that prevents degradation of HCV, produced a dose-dependent and prolonged decrease in HCV RNA levels in patients with chronic HCV genotype 1 infection. 

Miravirsen produced a dose-dependent and prolonged decrease in HCV RNA levels in patients with chronic HCV genotype 1 infection in this study. Miravirsen is a 15–nucleotide locked nucleic acid-modified antisense oligonucleotide which binds and sequesters miR-122. miR-122 is a liver micro RNA which complexes with the HCV genome, protecting it from nucleolytic degradation and innate immune responses. Thus, miravirsen exposes the HCV genome to host immune defenses. This stage IIa clinical trial demonstrates miravirsen’s advantages over current therapy including an improved side effect profile, reduced drug-drug interactions, no signs of resistance and once a month dosing.

Miravirsen is a promising new treatment for chronic HCV infection that could shorten treatment time, reduce the rate of relapse and offer the possibility of interferon-free regimens. However, due to its duration, this study could not identify long-term side effects of treatment. One of miR-122’s endogenous roles is as a tumor suppressor for hepatocellular carcinoma; therefore, long-term safety data for miravirsen are essential.

Click to read the study, published today in NEJM

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1. Miravirsen, an antisense inhibitor of a microRNA that prevents degradation of HCV, produced a dose-dependent and prolonged decrease in HCV RNA levels in patients with chronic HCV genotype 1 infection. 

This [randomized, double-blind, placebo–controlled] phase IIa dose-finding trial treated 36 therapy naïve HCV genotype 1 patients with compensated liver disease due to HCV, and a plasma HCV RNA level of more than 75,000 IU per milliliter, with miravirsen or placebo.  A total of 24 patients were treated with 3 mg, 5 mg or 7 mg/kg miravirsen (9 patients/group) subcutaneously in five weekly doses over a 29 day period. Patients were followed for a total of 18 weeks. Treatment with miravirsen resulted in a significant dose-dependent reduction in HCV RNA levels which was sustained beyond the administration of the drug. In five patients, miravirsen resulted in undetectable HCV RNA.

Virologic rebound was detected in 9 of 24 patients after discontinuation of miravirsen. However no resistance-associated mutations were detected In the HCV genome of any miravirsen patients. Most adverse events reported were mild, and there were no dose–dependent toxic effects or treatment discontinuation because of adverse effects. There was a sustained reduction in liver transaminases.

In sum: Miravirsen produced a dose-dependent and prolonged decrease in HCV RNA levels in patients with chronic HCV genotype 1 infection. Miravirsen is a 15–nucleotide locked nucleic acid-modified antisense oligonucleotide which binds and sequesters miR-122. miR-122 is a liver micro RNA which complexes with the HCV genome, protecting it from nucleolytic degradation and innate immune responses. Thus, miravirsen exposes the HCV genome to host immune defenses. This stage IIa clinical trial demonstrates miravirsen’s advantages over current therapy including an improved side effect profile, reduced drug-drug interactions, no signs of resistance and once a month dosing.

Miravirsen is a promising new treatment for chronic HCV infection that could shorten treatment time, reduce the rate of relapse and offer the possibility of interferon-free regimens. However, due to its duration, this study could not identify long-term side effects of treatment. One of miR-122’s endogenous roles is as a tumor suppressor for hepatocellular carcinoma; therefore, long-term safety data for miravirsen are essential.

Click to read the study, published today in NEJM 

By Jessica Mitchell and Mitalee Patil

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