Hepatitis C protease and polymerase inhibitors in development.
Hepatitis C infection (HCV) remains a global problem and the current anti-HCV therapies available in the clinic have sustained virologic response rates (SVR) of only about 50%, especially in HCV genotype 1-infected subjects. The SVR is even lower in HIV-HCV co-infected patients, estimated at only about 30-40%. However, exciting new research is under way to find new anti-HCV therapies. Presently, efforts to develop new anti-HCV agents for HCV-infected persons who fail pegylated interferon and ribavirin-based therapies have focused on inhibitors of key HCV enzymes such as the HCV NS3 protease and the NS5B polymerase. There are two protease inhibitors, telaprevir (VX-950, Vertex) and boceprevir (SCH 503034, Schering-Plough); and three polymerase inhibitors, valopicitabine (NM283, Idenix), R1626 (Roche), and HCV-796 (Viropharma) that have advanced to late-stage clinical trials. Of these aforementioned agents, telaprevir is the most advanced in clinical development. Early trial results on efficacy, safety, and HCV drug-resistance profiles of these novel agents will be discussed in this review paper.
Liu-Young
Gustine
G
Yale University School of Medicine, Department of Internal Medicine, Division of Infectious Diseases, 300 Cedar Street, S169, New Haven, Connecticut 06520, USA. gustine.liu-young@yale.edu
Kozal
Michael J
MJ
D000998:Antiviral Agents / Q000627:therapeutic use*; D005838:Genotype; D015658:HIV Infections / Q000150:complications; D016174:Hepacivirus / Q000235:genetics*; D006526:Hepatitis C / Q000150:complications / Q000188:drug therapy* / Q000235:genetics; D006801:Humans; D015337:Multicenter Studies as Topic; D009842:Oligopeptides / Q000627:therapeutic use*; D011392:Proline / Q000031:analogs & derivatives* / Q000627:therapeutic use; D011480:Protease Inhibitors / Q000627:therapeutic use*; D011741:Pyrimidine Nucleosides / Q000627:therapeutic use; D016032:Randomized Controlled Trials as Topic
D000998:Antiviral Agents; D009842:Oligopeptides; D011480:Protease Inhibitors; D011741:Pyrimidine Nucleosides; C486464:telaprevir; C512204:N-(3-amino-1-(cyclobutylmethyl)-2,3-dioxopropyl)-3-(2-((((1,1-dimethylethyl)amino)carbonyl)amino)-3,3-dimethyl-1-oxobutyl)-6,6-dimethyl-3-azabicyclo(3.1.0)hexan-2-carboxamide; D011392:Proline; C506207:valopicitabine