1. Telbivudine Versus Lamivudine in Chinese Patients with Chronic Hepatitis B: Results at 1 Year of a Randomized, Double-Blind Trial
HEPATOLOGY 2008;47:

2. Background →current therapies : efficacy limitations,
chronic HBV infection
end stage hepatitis B complications
cirrhosis, HCC : for over 1 million/yr deaths worldwide
→linked to high levels of circulating HBV DNA
→current therapies : efficacy limitations,
tolerability issues, or the emergence of resistance
→ new antiviral agents continue to be needed to maximize longer term suppression of HBV replication and improve therapeutic outcomes.

3. Telbivudine
orally bioavailable 1-nucleoside analogue
specific and potent inhibitor of HBV replication in vitro
no evidence of significant organ toxicity, genotoxicity, carcinogenicity, mitochondrial toxicity in vitro, teratogenicity, or embryofetal toxicity.
rapid and profound reductions in serum HBV DNA levels
→the GLOBE study

5. AIM
(1) to gain additional phase III data on telbivudine in Chinese patients with chronic hepatitis B
(2) to compare telbivudine and lamivudine in the relatively homogeneous Chinese patient population
(effects of ethnic variation could be minimized)
(3) to assess direct antiviral effect, reflected by serum HBV DNA reduction, as the primary efficacy measure

6. Patients and Methods
multicenter, double-blind, randomized phase III trial
for 2 years (104 weeks)
16 ~70 years
randomly assigned in a 1:1 ratio (once daily)
→600 mg of telbivudine + lamivudine placebo
→100 mg of lamivudine + telbivudine placebo
Inclusion criteria
active viral replication (positive serum HBsAg)
HBeAg(+) compatible with chronic hepatitis B
HBeAg(+) or HBeAg(-)
s-HBV DNA ≥ 6 log10 copies/mL
s-ALT levels ≥ 1.3 times ULN (but <10 times ULN )
liver Bx within 12 months prior to randomization

7. Primary efficacy endpoint : s-HBV DNA reduction at 1 year (52 wks)
→with treatment continuing for a second year to assess longer term efficacy and safety
Secondary efficacy measures
proportions of patients with s-HBV DNA reduction < 5 log10 copies/mL on two successive visits
HBV DNA reductions to PCR-undetectable levels
ALT normalization
HBeAg loss and seroconversion(for HBeAg-positive patients)
therapeutic response
HBeAg(+) : HBV DNA reduced <5 log10 copies/mL coupled with HBeAg loss or ALT normalization
HBeAg(-) : HBV DNA reduced < 5 log10 coupled with serum ALT normalization

8. Table 1. Baseline Demographic and Disease Features

9. Fig. 1. Reduction of serum HBV DNA from baseline
P<0.001

10. Table 2. Efficacy in HBeAg-Positive Patients
Therapeutic response 100% vs 82%
Primary treatment failure 0% vs 5%

11. Fig. 2. Time to PCR-undetectable serum HBV DNA

12. Efficacy differences also generally favored telbivudine
Discussion
Efficacy differences also generally favored telbivudine
in the much smaller HBeAg-negative subpopulation.
The proportion of eligible HBeAg-negative patients was
expected to be relatively low
Resistance to telbivudine after 1 year was less than half that observed with lamivudine
consistent with the previous phase III GLOBE trial
did not reach statistical significance in the present study
→presumably because of the more limited sample size in comparison with the GLOBE study

13. Conclusion
In Chinese patients with chronic hepatitis B, telbivudine treatment for 52 weeks provided greater antiviral and clinical efficacy than lamivudine, with less resistance.