Telbivudine (Tyzeka) May Be Effective for Chronic Hepatitis B Treatment after Failure of Adefovir (Hepsera)

By Liz Highleyman

Several nucleoside and nucleotide analog agents are active against hepatitis B virus (HBV), but development of drug resistance is a barrier to long-term treatment effectiveness, especially when drugs are used as monotherapy,

In the February 2009 issue of Antiviral Research, Maria Seifer from Idenix Pharmaceuticals and colleagues described the resistance profile of the company's anti-HBV drug telbivudine (Tyzeka).

In addition to telbivudine, a nucleoside analog inhibitor of HBV polymerase, approved hepatitis B drugs also include 2 other nucleoside analogs -- lamivudine (Epivir-HBV) and entecavir (Baraclude) -- and 2 nucleotide analog inhibitors adefovir (Hepsera) and tenofovir (Viread, also in the Truvada combination pill with emtricitabine).

In this laboratory study, the investigators analyzed the resistance profiles of these agents by treating HepG2 culture cells stably infected with wild-type or mutant HBV genomes carrying known resistance mutations.

Results

Telbivudine was not active against HBV strains carrying the lamivudine mutations L180M and M204V/I.

However, it remained active against the M204V single mutation in vitro, potentially explaining the difference in resistance profiles between telbivudine and lamivudine.

The activity of telbivudine, lamivudine, and entecavir was reduced 353-fold to >1000-fold against HBV genomes with the known telbivudine-resistance mutations M204I and L80I/M204I.

Adefovir and tenofovir exhibited no more than a 3-fold to 5-fold change in activity against telbivudine-resistance HBV mutants.

Conversely, against HBV cell lines expressing the adefovir-resistance mutations N236T and A181V, or the A194T mutant associated with tenofovir resistance, telbivudine remained active, with only 0.5-fold to 1.0-fold changes.

In conclusion, the study authors wrote, "These in vitro results indicate that nucleoside and nucleotide drugs have different cross-resistance profiles."

Based on these findings, they suggested, "The addition of telbivudine to ongoing adefovir therapy could provide effective antiviral therapy to patients who develop adefovir resistance."

3/10/09

Reference
M Seifer, A Patty, I Serra, and others. Telbivudine, a nucleoside analog inhibitor of HBV polymerase, has a different in vitro cross-resistance profile than the nucleotide analog inhibitors adefovir and tenofovir. Antiviral Research 81(2): 147-155. February 2009. (Abstract).