Clevudine for hepatitis B.
Clevudine is distinguished from other oral agents by its sustained suppression of HBV DNA for several months after cessation of therapy, according to a comprehensive review of hepatitis B in the 2 October 2008 issue of the New England Journal of Medicine. Clevudine is differentiated by i) an unusual activation pathway to the biochemically active triphosphate; ii) a mechanism of action of clevudine triphosphate that inhibits multiple steps of the hepatitis B virus (HBV) intracellular life cycle; iii) a long half-life and iv) significant reduction of covalently closed circular DNA (cccDNA) in animal models. Clevudine was approved and is marketed in South Korea based on two 24-week phase III trials vs. placebo. In these studies with treatment-naïve patients, 59% of 248 HBeAg-positive patients had undetectable HBV DNA after 24 weeks of treatment compared with 92% of 89 HBeAg-negative patients, while the percentage of patients with normal liver enzymes was 68% in the HBeAg-positive patients and 75% in the HBeAg-negative patients (all statistically significant versus placebo). Follow-up studies include trials vs. lamivudine as well as a phase IV study of long-term clevudine. Larger and longer phase III trials in the United States, European Union, Asia and South America of clevudine vs. adefovir are ongoing. An ANRS-sponsored trial of clevudine vs. tenofovir vs. the combination of the two agents is poised to begin. Literature published through November 2008 and presentations from the 59th annual meeting of the American Association for the Study of Liver Diseases held 31 October to 4 November 2008 are included.
Anderson
David Leif
DL
Medical Information Department, Prous Science, Barcelona, Spain. leifanderson@aol.com
D000818:Animals; D000998:Antiviral Agents / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D001086:Arabinofuranosyluracil / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D019694:Hepatitis B, Chronic / Q000188:drug therapy*; D006801:Humans
D000998:Antiviral Agents; D001086:Arabinofuranosyluracil; C034935:clevudine