Phase III Comparison of Telbivudine vs Lamivudine in Patients with Chronic Hepatitis B: Efficacy, Safety, and Predictors of Response at 1 Year
N Bzowej,1 C-L Lai,2 E Gane,3 Y-F Liaw,4 S Thongsawat,5 Y Wang,6 Y Chen,7 J Heathcote,8 J Rasenack,9 N Naoumov,10 G Chao,11 B Fielman,11 N Brown11 and the GLOBE Study Group
1Sutter Health, San Francisco, CA; 2University of Hong Kong; 3Middlemore Hospital, Auckland, NZ; 4Chang Gung University and Memorial Hospital, Taipei, Taiwan; 5Chiang Mai University, Chiang Mai, Thailand; 6Military Medical University, Chongqing, China; 7Zhejiang University College of Medicine, Hangzhou, China; 8Toronto Western Hospital, Toronto, ON; 8Albert Ludwigs Universität, Freiburg, Germany; 10University College, London, UK; 11Idenix Pharmaceuticals, Cambridge, MA
Background: The GLOBE trial is a 2-year phase III randomized comparison of telbivudine vs lamivudine in 921 HBeAg-positive and 446 HBeAg-negative adults with chronic hepatitis B from 20 countries. We report the primary efficacy and safety results at 52 weeks and preliminary results at 76 weeks and determine predictors of efficacy in this international trial.
Methods: Key entry criteria were HBsAg+, HBeAg+ or HBeAg-, HBV DNA >6 log10 by COBAS PCR assay, ALT 1.3-10 xULN, and compensated liver disease. Outcomes were assessed according to baseline demographics (age, gender, ethnicity) and disease factors (HBV genotype, HBV DNA level, ALT level), and early on-treatment responses (HBV DNA and ALT levels at Weeks 12 and 24).
Results:
|
HBeAg (+)
|
HBeAg (-)
|
|
Week 52
|
Week 76
|
Week 52
|
Week 76
|
Response
|
LdT
|
Lam
|
LdT
|
Lam
|
LdT
|
Lam
|
LdT
|
Lam
|
n
|
458
|
463
|
458
|
463
|
163
|
165
|
163
|
165
|
log10 HBV DNA ¯
|
6.5*
|
5.5
|
6.6*
|
5.2
|
5.2*
|
4.4
|
5.3
|
4.7
|
%
PCR neg
|
60*
|
40
|
69*
|
41
|
88*
|
71
|
84*
|
67
|
% Histologic Resp
|
65*
|
56
|
-
|
-
|
67
|
66
|
-
|
-
|
%
ALT normalized
|
77
|
75
|
78*
|
68
|
74
|
79
|
76
|
64
|
%
Therapeutic Resp‡
|
75*
|
67
|
75*
|
58
|
75
|
77
|
75
|
70
|
% HBeAg loss
|
26
|
23
|
40*
|
26
|
-
|
-
|
-
|
-
|
%
HBV resist.
|
3*
|
8
|
-
|
-
|
2*
|
9
|
-
|
-
|
%
1º Treatment Failure†
|
5*
|
13
|
-
|
-
|
<1
|
3
|
-
|
-
|
†HBV DNA never <5 log10
copies/mL
‡HBV DNA <5 log10 plus ALT normalization or HBeAg loss
*p<0.01, telbivudine vs lamivudine
|
At Week 52, telbivudine was superior to lamivudine on all measures of direct antiviral efficacy in both HBeAg+ and HBeAg- patients (log10 HBV DNA reduction, % PCR negative, resistance, treatment failure). In HBeAg+ pts, HBeAg loss was higher in patients with baseline ALT >2xULN (“interferon eligible” population): 32% and 49% for telbivudine at Weeks 52 and 76 respectively, vs. 27% and 29% for lamivudine.
Conclusions: After 1 year, telbivudine showed significantly greater direct antiviral efficacy than lamivudine in HBeAg-positive and HBeAg-negative patients with chronic hepatitis B, with less primary treatment failure and resistance. Early HBV DNA response was the strongest predictor of 1-year efficacy outcomes.
05/23/06
Reference
N Bzowej, C-L Lai, E Gane, and others. Phase III Comparison of Telbivudine vs Lamivudine in Patients with Chronic Hepatitis B: Efficacy, Safety, and Predictors of Response at 1 Year. Abstract 482. DDW 2006. May 20-25, 2006. Los Angeles, CA.
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