Boceprevir: a novel NS3/4 protease inhibitor for the treatment of hepatitis C.

Abstract

Hepatitis C virus (HCV) infection affects over 170 million people worldwide and is the most common blood-borne infection in the United States. Standard treatment with peginterferon alfa-ribavirin results in low sustained virologic response (SVR) rates in many patients, especially those who are African-American, are coinfected with human immunodeficiency virus (HIV), or have liver cirrhosis. Because of suboptimal SVR rates, new direct-acting antiviral agents that target HCV viral replication steps are in development. Boceprevir is one of the novel NS3/4A protease inhibitors that was recently approved by the U.S. Food and Drug Administration. We evaluated the literature regarding boceprevir by performing a MEDLINE search (January 1996-July 2011) to identify relevant clinical trials. Abstracts and poster and oral presentations from hepatology and HIV conferences were also reviewed. Potent anti-HCV activity was seen in clinical trials with boceprevir when it was studied in HCV genotype 1-infected patients who were naïve to or had experience with HCV therapy. Data with boceprevir in HIV-HCV-coinfected patients are currently lacking; however, initial data on drug-drug interactions between boceprevir and antiretrovirals have become available. Resistance to boceprevir has been evaluated in trials as well, although more data are needed in this area. The most common adverse events with boceprevir included anemia and dysgeusia. Based on available data, boceprevir is one of the promising novel direct-acting antiviral agents that will likely reshape the treatment of patients with HCV infection.

• Authors: Olga M Klibanov, Stephen B Vickery, Jacqueline L Olin, Lisa S Smith, Shannon H Williams
• Journal: Pharmacotherapy (Pharmacotherapy) Vol. 32 Issue 2 Pg. 173-90 (Feb 2012) ISSN: 1875-9114 [Electronic] United States
• PMID: 22392426 (Publication Type: Journal Article, Review)
• Copyright: © 2012 Pharmacotherapy Publications, Inc.

Chemical References

• NS3 protein, hepatitis C virus
• NS4 protein, hepatitis C virus
• Protease Inhibitors
• Viral Nonstructural Proteins
• 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
• Proline

Topics

• Clinical Trials as Topic
• Hepatitis C (drug therapy, enzymology)
• Humans
• Proline (analogs & derivatives, pharmacology, therapeutic use)
• Protease Inhibitors (pharmacology, therapeutic use)
• Treatment Outcome
• Viral Nonstructural Proteins (metabolism)