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.