Hepatitis C therapy with HCV NS5B polymerase inhibitors. (June 2013)

• Record Type: Journal Article
• Authors: Soriano, Vincent; Vispo, Eugenia; de Mendoza, Carmen; Labarga, Pablo; Fernandez-Montero, Jose Vicente; Poveda, Eva; Treviño, Ana; Barreiro, Pablo
• Is Part Of: Expert opinion on pharmacotherapy. Volume 14:Number 9(2013)
• Page Start: 1161
• Page End: 1170
• Publication Date: 2013-06
• Subjects: drug resistance -- hepatitis C -- interferon-free -- mericitabine -- nucleoside analogs -- polymerase inhibitors -- sofosbuvir; Chemotherapy -- Periodicals; 615.5805
• DOI: 10.1517/14656566.2013.795543
• Languages: English
• ISSNs: 1465-6566

Abstract

Abstract : Introduction: Several HCV polymerase inhibitors are in advanced stages of clinical development. They are nucleos(t)ide and non-nucleoside analogs. Nucleos(t)ides inhibit viral replication acting as chain terminators whereas non-nucleosides block allosterically the HCV polymerase. Sofosbuvir is an uridine analog and currently the most promising HCV polymerase inhibitor, being active across all HCV genotypes. It has good tolerability and a robust barrier to resistance. In contrast, non-nucleoside analogs have low to moderate antiviral potency, a low barrier to resistance and inhibit only HCV genotype 1. Areas covered: Studies conducted with distinct HCV polymerase inhibitors as part of interferon-free combinations have opened a new landscape in which shorter treatment duration and all-oral regimens are envisioned as the future curative treatment for most chronic hepatitis C patients. Expert opinion: Antiviral drug development for HCV is progressing at a feverish pace. Amongst HCV polymerase inhibitors, sofosbuvir has positioned as unique companion with ribavirin as therapy for most HCV genotypes 2 or 3, and along with NS5A inhibitors for other HCV genotypes. Non-nucleoside HCV polymerase inhibitors are being developed only as part of all-oral combinations with protease inhibitors. The expected high cost of DAAs will preclude their prompt and wider use, allowing room for using alternative cheaper options in easier-to-treat patient populations.