title: Rapid and sharp decline in HCV upon monotherapy with NS3 protease inhibitor, ACH-1625.
abstract: BACKGROUND
  ACH-1625 is a linear peptidomimetic inhibitor that non-covalently binds to HCV NS3 protease with high potency and specificity. Short-term monotherapy of HCV genotype-1 infection with ACH-1625 was found to be safe and resulted in ≥3.3 log(10) IU/ml mean viral load reduction. These viral load decay data were analysed to compare HCV dynamics with prior reports and estimate the antiviral efficiency of ACH-1625.
  
  
  METHODS
  Drug efficiency was estimated by analysing the viral decay following initiation of up to 5 days of monotherapy with ACH-1625 in 36 chronically infected HCV genotype-1 patients. During this monotherapy study, ACH-1625 was administered either twice-a-day for 4.5 days or once daily for 5 days at 5 different dose levels in 36 patients.
  
  
  RESULTS
  A sharp viral decay during the first 48 h following the initiation of ACH-1625 treatment afforded high drug efficiency estimates (≥0.9934). In addition, an increase in the estimated drug efficiency was observed with increasing ACH-1625 dose. The observed anti-HCV response was fairly uniform in this proof-of-concept study across the population of 36 patients.
  
  
  CONCLUSIONS
  Estimates of the treatment-independent viral kinetics parameters were consistent with prior reports and the estimated drug efficiency of ACH-1625 monotherapy was very high (≥0.9934) in fasted and fed states.
authors.affiliation: Achillion Pharmaceuticals, Inc., New Haven, CT, USA. aagarwal@achillion.com
authors.forename: Atul
authors.initials: A
authors.lastname: Agarwal
authors.forename: Bao
authors.initials: B
authors.lastname: Zhang
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Olek
authors.forename: Heather
authors.initials: H
authors.lastname: Robison
authors.forename: Lisa
authors.initials: L
authors.lastname: Robarge
authors.forename: Milind
authors.initials: M
authors.lastname: Deshpande
mesh_terms: D000465:Algorithms; D000998:Antiviral Agents / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use*; D005838:Genotype; D017320:HIV Protease Inhibitors / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use*; D016174:Hepacivirus / Q000502:physiology; D019698:Hepatitis C, Chronic / Q000188:drug therapy* / Q000821:virology*; D006801:Humans; D007700:Kinetics; D008954:Models, Biological; D019562:Viral Load
chemical_list: D000998:Antiviral Agents; D017320:HIV Protease Inhibitors