Persson R, et al. Journal of Hepatology, 2012, 56, S477.
Miravirsen (MIR), a β-D-oxy-Locked Nucleic Acid (LNA)-modified phosphorothioate antisense oligonucleotide, targets microRNA-122 (miR-122), a critical host factor for hepatitis C virus (HCV) replication. Unlike traditional therapies, MIR exhibits a high genetic barrier to resistance and does not rely on CYP450 metabolism, underscoring its potential as a groundbreaking antiviral agent.
A Phase 2a clinical trial investigated the safety, pharmacokinetics (PK), and antiviral efficacy of MIR in treatment-naive patients with chronic genotype 1 HCV infection. MIR was administered subcutaneously at doses of 3, 5, or 7 mg/kg weekly for five weeks, with three patient cohorts (9 MIR; 3 placebo/cohort). Plasma MIR levels were quantified via hybridization-dependent ELISA at peak (2 hours post-dose) and trough (168 hours post-dose) intervals.
Results revealed a dose-dependent increase in plasma MIR concentrations, both at peak and trough levels, indicating robust liver exposure. MIR exhibited a prolonged plasma terminal half-life of 37 days, allowing for sustained trough concentrations with successive weekly doses. Viral load reductions correlated directly with plasma MIR concentrations, becoming significant by the third dose and persisting for weeks to months post-dosing. These prolonged pharmacodynamic effects align with MIR's PK profile and liver-specific activity.
