Miravirsen dosing in chronic hepatitis C patients results in decreased microRNA‐122 levels without affecting other microRNAs in plasma

Abstract

Summary Background MicroRNA‐122 (miR‐122) is an important host factor for hepatitis C virus replication. Administration of miravirsen, an anti‐miR‐122 oligonucleotide, resulted in a dose dependent and prolonged decrease in HCV RNA levels in chronic hepatitis C patients. Aim To assess the plasma level of various miRNAs in patients dosed with miravirsen. Methods We included 16 of 36 chronic hepatitis C patients who received five injections of either 3 mg/kg (n = 4), 5 mg/kg (n = 4), 7 mg/kg (n = 4) miravirsen or placebo (n = 4) over a 4‐week period in a double‐blind, randomised phase 2a study. Plasma levels of 179 miRNAs were determined by qPCR and compared between patients dosed with miravirsen or placebo. Results Median plasma miR‐122 level at baseline in patients receiving miravirsen was 3.9 × 103 compared to 1.3 × 104 copies/4 μL in placebo‐dosed patients (P = 0.68). At week 1, 4, 6 and 10/12, patients dosed with miravirsen had respectively a median 72‐fold, 174‐fold, 1109‐fold and 552‐fold lower expression of miR‐122 than at baseline (P = 0.001, as compared to patients receiving placebo). At week 4 of dosing, miRNA‐profiling demonstrated a significant lower expression of miR‐210 and miR‐532‐5p compared to baseline (3.0 and 4.7‐fold lower respectively). However, subsequent longitudinal analysis showed no significant differences in miR‐210 and miR‐532‐5p plasma levels throughout the study period. Conclusions We demonstrated a substantial and prolonged decrease in plasma miR‐122 levels in patients dosed with miravirsen. Plasma levels of other miRNAs were not significantly affected by antagonising miR‐122.

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