Hepsera® has 0% genotypic resistance at 1 year in a broad range of patient types in clinical development studies.
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- HBeAg–
(Study 438, n=123)3 - HBeAg+
(Study 437, n=171)2
(Hepsera added to LAM) - LAM-R, pre- and post-transplant
(Study 435, n=96)5 - LAM-R, HIV/HBV coinfection
(Study 460i, N=35)1* | *Study 460i1,11 - An open-label, prospective, 5-year trial designed to assess the safety and efficacy of Hepsera in the treatment of lamivudine-resistant HIV/HBV-coinfected patients (N=35).
- HBeAg– patients: Cumulative probability of genotypic resistance was 0%, 3%, 11%, 19%, and 30% at years 1, 2, 3, 4, and 5, respectively.1
- HBeAg+ patients: 65 continued on long-term treatment after a median duration on Hepsera of 235 weeks (range, 110–279 weeks). 16 of 38 (42%) patients were identified with Hepsera resistance-associated mutations in the setting of virologic failure (confirmed increase of ≥1 log10 HBV DNA copies/mL above nadir or never suppressed below 10³ copies/mL).1
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when Hepsera was added for combination therapy (HIV/HBV-coinfected patients, Study 460i1,11, and pre- and post-transplant patients, Study 4351,5,†). | 
† In Study 435, at week 72, 4 patients who developed Hepsera-associated mutations (A181T/V and/or N236T) were on Hepsera monotherapy when they developed resistance.
Backed by up to 5 years of resistance data based on prescribing information1
Not intended to imply comparative efficacy or appropriateness of therapy.
§ Data reported at week 72.
The clinical significance of in-vitro observations is unknown.
**HBV mutants with the Hepsera resistance-associated mutation rtA181V showed a range of decreased susceptibilities to lamivudine (1- to 14-fold decrease),1 entecavir (12-fold decrease),1 and telbivudine (3- to 5-fold decrease).9 In patients with the rtA181V mutation (n=2) or the rtN236T mutation (n=3), reductions in serum HBV DNA of 2.4 to 3.1 and 2.0 to 5.1 log10 copies/mL, respectively, were observed when treatment with lamivudine was added to treatment with Hepsera.1 Recombinant HBV genomes encoding Hepsera resistance-associated substitutions at either N236T or A181V had 0.3- and 1.1-fold shifts in susceptibility to entecavir in cell culture, respectively.8
†† Adapted from Locarnini, et al12 and the entecavir full prescribing information.8
‡‡ The A181T mutation was associated with a < 2-fold increase in EC50 (in vitro) and was also seen in HBV clinical studies of LAM.
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