Telbivudine: an upcoming agent for chronic hepatitis B

Abstract

Telbivudine, the prototype member of β-l-2´-deoxynucleosides, has proven to be safe in in vitro animal and human studies. Telbivudine given for 4 weeks resulted in an 8-log reduction of woodchuck hepatitis virus DNA, and a 3.8-log reduction of hepatitis B virus DNA in human. After 52 weeks of telbivudine treatment there was an approximate 6-log reduction of hepatitis B virus DNA levels, hepatitis B virus DNA became undetectable by PCR assay in 61% of patients. Its antiviral efficacy is significantly better than lamivudine. The probability of tyrosine-methionine-aspartate-aspartate mutations at 52 weeks of telbivudine therapy is low, although still occurring in 4.5% of patients. After 96 weeks of therapy, the proportion of patients with undetectable hepatitis B virus DNA by PCR assay increased to 71%, but genotypic resistance also increased to 18.2%, with only 4.5% showing alanine aminotransferase flares. Telbivudine is probably one of the most potent antiviral agents for hepatitis B virus that will become available in the near future.

Keywords::

• HBV DNA
• lamivudine
• telbivudine
• viral suppression
• tyrosine-methionine-aspartate-aspartate (YMDD) mutations