Telbivudine was recently approved for the treatment of
chronic hepatitis B. Phase III studies indicated its
antiviral potency with 6- to 6.5-log copies/mL reductions in
hepatitis B DNA levels at year 1, comparable to other potent agents such as
entecavir or
tenofovir. Genotypic resistance rates, however, reached 25% at year 2 in
hepatitis B e-antigen positive subjects and 11% in
hepatitis B e-antigen negative subjects, preventing it from becoming a preferred first-line
drug for
hepatitis B. Furthermore, its signature resistance mutation (a change from
methionine to
isoleucine at position 204 in the
reverse transcriptase domain of the
hepatitis B polymerase) also confers cross-resistance to
entecavir,
lamivudine, and
emtricitabine.
Telbivudine is well tolerated, with elevations in
creatine phosphokinase being the most common abnormality observed in clinical trials. Most often, elevations were asymptomatic. Future research in
hepatitis B will focus on the best ways to use existing
therapies, including
telbivudine, sequentially or in combination in order to maximize viral suppression and minimize the development of
antiviral resistance.