Preclinical Profile and Clinical Efficacy of a Novel Hepatitis C Virus NS5A Inhibitor, EDP-239.

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.).

authors

Owens CM,Brasher BB,Polemeropoulos A,Rhodin MH,McAllister N,Peng X,Wang C,Ying L,Cao H,Lawitz E,Poordad F,Rondon J,Box TD,Zeuzem S,Buggisch P,Lin K,Qiu YL,Jiang L,Colvin R,Or YS

doi

10.1128/AAC.00808-16

subject

Has Abstract

pub_date

2016-09-23 00:00:00

pages

6207-15

issue

10

eissn

0066-4804

issn

1098-6596

pii

AAC.00808-16

journal_volume

60

pub_type

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