Resiquimod Reduces HCV Viral Load, but Causes Side Effects Similar to Interferon

Given the limited efficacy and high incidence of side effects with interferon-based therapy for hepatitis C, researchers have explored numerous other treatment options.

As reported in the August 2007 Journal of Hepatology, investigators conducted 2 studies to explore the safety, pharmacokinetics, and pharmacodynamics of oral administration of resiquimod. Resiquimod is a toll-like receptor 7 and 8 agonist that has been shown to induce endogenous interferon-alpha production in people with chronic hepatitis C virus infection.

In a multicenter, double-blind Phase IIa study, 12 hepatitis C patients were randomly assigned to receive resiquimod (0.01 mg/kg) for 4 weeks, while 4 control subjects received placebo. In addition, in a single-center study in France, 6 subjects received 0.01 mg/kg resiquimod, 11 received 0.02 mg/kg resiquimod, and 6 received placebo.

Results

• The 0.01 mg/kg dose of resiquimod was generally well tolerated.

• 2 patients in the 0.2 mg/kg dose arm discontinued treatment.

• More subjects reported severe adverse events using the 0.02 mg/kg dose.

• Adverse events were consistent with systemic cytokine induction, including fever, headache, shivering, and lymphopenia.

• Mean maximum serum resiquimod concentrations were 3.82 and 7.55 in the 2 dose arms.

• In the 0.02 mg/kg dose group, 2 patients had maximal HCV RNA reductions of at least 1 log, 3 had reductions of 2 log, and 1 had a reduction of 3 log.

• In most cases, HCV viral load reductions were transient, rising again after the dosing period.

• Interferon-alpha levels appeared correlated with decreases in HCV viral titer and lymphocyte counts, as well as increases in neutrophil counts.

Conclusion

In conclusion, the authors wrote, "Oral administration of resiquimod 0.02 mg/kg transiently reduced viral levels but was associated with adverse effects similar to interferon-alpha."

07/31/07

Reference
PJ Pockros, D Guyader, H Patton, and others. Oral resiquimod in chronic HCV infection: Safety and efficacy in 2 placebo-controlled, double-blind phase IIa studies. Journal of Hepatology 47(2): 174-182. August 2007.