Preclinical profile and clinical efficacy of a novel hepatitis C virus NS5A inhibitor, EDP-239

Christopher M. Owens, Bradley B. Brasher, Alex Polemeropoulos, Michael H.J. Rhodin, Nicole McAllister, Xiaowen Peng, Ce Wang, Ying Lu, Hui Cao, Eric Lawitz, Fred Poordad, Juan Rondon, Terry D. Box, Stefan Zeuzem, Peter Buggisch, Kai Lin, Yao Ling Qiu, Lijuan Jiang, Richard Colvin, Yat Sun Or

Research output: Contribution to journalArticlepeer-review

3 Scopus citations

Abstract

EDP-239, a novel hepatitis C virus (HCV) inhibitor targeting nonstructural protein 5A (NS5A), has been investigated in vitro and in vivo. EDP-239 is a potent, selective inhibitor with potency at picomolar to nanomolar concentrations against HCV genotypes 1 through 6. In the presence of human serum, the potency of EDP-239 was reduced by less than 4-fold. EDP-239 is additive to synergistic with other direct-acting antivirals (DAAs) or host-targeted antivirals (HTAs) in blocking HCV replication and suppresses the selection of resistance in vitro. Furthermore, EDP-239 retains potency against known DAA- or HTA-resistant variants, with half-maximal effective concentrations (EC50s) equivalent to those for the wild type. In a phase I, single-ascending-dose, placebo-controlled clinical trial, EDP-239 demonstrated excellent pharmacokinetic properties that supported once daily dosing. A single 100-mg dose of EDP-239 resulted in reductions in HCV genotype 1a viral RNA of >3 log10 IU/ml within the first 48 h after dosing and reductions in genotype 1b viral RNA of >4-log10 IU/ml within 96 h. (This study has been registered at ClinicalTrials.gov under identifier NCT01856426.).

Original languageEnglish (US)
Pages (from-to)6207-6215
Number of pages9
JournalAntimicrobial agents and chemotherapy
Volume60
Issue number10
DOIs
StatePublished - Oct 2016

ASJC Scopus subject areas

  • Pharmacology
  • Pharmacology (medical)
  • Infectious Diseases

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