Hepatitis B Patients Who Had Incomplete Response or Relapse on Adefovir (Hepsera)
Respond Well to Entecavir (Baraclude)
Several nucleoside/nucleotide analog agents are
approved for patients with chronic hepatitis B virus
(HBV) infection, but development of drug resistance presents a challenge to
long-term treatment success.
As reported at the 44th
Annual Meeting of the European Association for the Study of the Liver (EASL 2009)
last week in Copenhagen, Nancy Leung and an international team of colleagues evaluated
the effectiveness of entecavir (Baraclude)
in patients who experienced incomplete response during treatment with adefovir
(Hepsera) or viral relapse after stopping adefovir. Entecavir was chosen because
laboratory studies indicate that it is does not share cross-resistance with adefovir.
previous trial, ETV-079 (also known as E.A.R.L.Y.),was a randomized, open-label
study comparing the viral kinetics, efficacy, and safety of 0.5 mg/day entecavir
versus 10 mg/day adefovir in nucleoside/nucleotide-naive hepatitis B "e"
antigen (HBeAg) positive patients. After 48 weeks of treatment, participants in
both arms of that study were eligible to join a rollover study, ETV-901, and receive
treatment with 1.0 mg/day entecavir.
A total of 24 participants rolled
over into ETV-901; 18 of them had either failed to achieve undetectable HBV DNA
(< 300 copies/mL) while taking adefovir (n = 14) or relapsed after stopping
adefovir (n = 4). Among participants who relapsed while off treatment between
ETV-079 and ETV-901, the treatment gap ranged from 1 to 128 days. At entry into
ETV-901, the overall median HBV DNA level was just over 6 log10 copies/mL. More
than 90% of ETV-901 participants were of Asian ethnicity.
Patients who were non-responders or relapsers with adefovir experienced rapid
decline in HBV DNA when they switched to 1.0 mg/day entecavir.
The mean reductions in HBV DNA were 4.54 log10 copies/mL at week 24 and 5.75 log10
copies/mL at week 48.
At week 24, 50% of patients who switched achieved HBV DNA < 300 copies/mL.
At week 48, 89% achieved HBV DNA < 300 copies/mL.
69% achieved ALT normalization by week 24, and 78% did so by week 48.
19% experienced HBe seroconversion by week 24, and 22% did so by week 48.
No participants experienced virological rebound while receiving entecavir in ETV-901.
Switching to entecavir was generally well tolerated, with no unexpected side effects
based on prior studies.
findings led the investigators to conclude, "The majority of patients who
had incomplete virological response or experienced virological relapse following
adefovir treatment in study ETV-079 had rapid reductions in HBV DNA when switched
to entecavir in study ETV-901."
In a related study also presented
at the conference, researchers from Bristol-Myers Squibb followed patients receiving
entecavir for up to 6 years. They found that emergence of entecavir resistance
was rare (1.2%) among nucleoside-naive patients. The genetic barrier to resistance
is lower, however, in patients who fail treatment with lamivudine
(Epivir-HBV), and the investigators suggested this subgroup might benefit
from combination therapy.
Queen Mary's Hospital, University of Hong
Kong, Hong Kong, Chin; Whitman-Walker Clinic, Washington, DC; Toronto General
Hospital, Toronto, Canada; Liver Disease Prevention Center, Thomas Jefferson University
Hospital, Philadelphia, PA; Health Sciences Center, Edmonton, Canada; Chang Gung
Memorial Hospital, Chang Gung University College of Medicine, Taipei, Taiwan;
Singapore General Hospital, Singapore; China Medical University Hospital, Taichung,
Taiwan; Alice Ho Miu Ling Nethersole Hospital, Hong Kong, China; Research and
Development, Bristol-Myers Squibb Company, Wallingford, CT and Princeton, NJ.
Leung, C-L Lai, R Elion, and others. Entecavir (ETV) therapy in chronic hepatitis
B patients previously treated with adefovir (ADV) with incomplete response on-treatment
or relapse off-treatment. 44th Annual Meeting of the European Association for
the Study of the Liver (EASL 2009). Copenhagen, Denmark. April 22-26, 2009.
Tenney, KA Pokornowski, RE Rose, and others. Entecavir maintains a high genetic
barrier to HBV resistance through 6 years in naive patients. EASL 2009. Copenhagen,
Denmark. April 22-26, 2009.
2009 MAIN PAGE
2009 Conference Coverage
HIV and Hepatitis.com Highlights from EASL 2009
Conference on Retroviruses and Opportunistic Infections (CROI 2009)
by HIV and Hepatitis.com - February 8 - 11, 2009, Montreal
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of the 15th Conference on Retroviruses and Opportunistic Infections (CROI 2009)
- Coverage by HIV and Hepatitis.com, February 8 - 11, 2009, Montreal