Back to Search
Start Over
Filibuvir, a non-nucleoside NS5B polymerase inhibitor for the potential oral treatment of chronic HCV infection.
- Source :
-
IDrugs : the investigational drugs journal [IDrugs] 2010 Dec; Vol. 13 (12), pp. 938-48. - Publication Year :
- 2010
-
Abstract
- Filibuvir (PF-868554), being developed by Pfizer, is an orally administered, non-nucleoside inhibitor of the HCV NS5B RNA-dependent RNA polymerase for the potential treatment of chronic HCV infection. An estimated 180 million people worldwide are infected with HCV and at risk of developing chronic liver diseases that can lead to cirrhosis or hepatocellular carcinomas. HCV infection is the main cause of liver transplantation in industrialized nations. Filibuvir is a potent and specific inhibitor of the virally-encoded NS5B polymerase, and inhibited genotype 1 subgenomic HCV replication in the cell-based replicon system. Filibuvir demonstrated a good pharmacokinetic profile and oral bioavailability in preclinical animal studies, which is consistent with twice-daily dosing in humans. In phase I and a IIa clinical trial in treatment-naïve patients infected with genotype 1 HCV, filibuvir monotherapy or in combination with pegylated IFNα2a/ribavirin (the standard of care [SoC] for HCV infection) for up to 4 weeks significantly reduced HCV RNA levels compared with placebo or SoC alone. The incidence and severity of adverse events were similar to SoC and placebo. At the time of publication, phase I pharmacokinetic clinical trials were ongoing in healthy volunteers and a phase IIb clinical trial was assessing filibuvir in combination with SoC for up to 24 weeks in treatment-naïve patients infected with genotype 1 HCV. Results of this trial will help to characterize the potential of this drug class for the treatment of HCV infections.
- Subjects :
- Administration, Oral
Animals
Antiviral Agents adverse effects
Antiviral Agents pharmacokinetics
Antiviral Agents pharmacology
Hepacivirus drug effects
Humans
Nucleic Acid Synthesis Inhibitors adverse effects
Nucleic Acid Synthesis Inhibitors pharmacokinetics
Nucleic Acid Synthesis Inhibitors therapeutic use
Pyrones adverse effects
Pyrones pharmacokinetics
Triazoles adverse effects
Triazoles pharmacokinetics
Antiviral Agents therapeutic use
Hepatitis C, Chronic drug therapy
Nucleic Acid Synthesis Inhibitors pharmacology
Pyrones pharmacology
Pyrones therapeutic use
RNA-Dependent RNA Polymerase antagonists & inhibitors
Triazoles pharmacology
Triazoles therapeutic use
Viral Nonstructural Proteins antagonists & inhibitors
Subjects
Details
- Language :
- English
- ISSN :
- 2040-3410
- Volume :
- 13
- Issue :
- 12
- Database :
- MEDLINE
- Journal :
- IDrugs : the investigational drugs journal
- Publication Type :
- Academic Journal
- Accession number :
- 21154154