Chronic Hepatitis B Patients Who Had Incomplete Response or Relapse on Adefovir (Hepsera) Respond Well to Entecavir (Baraclude)

By Liz Highleyman

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.

A 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.

Results

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.

These 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.

5/01/09

References

N 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.

DJ 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.

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15th Conference on Retroviruses and Opportunistic Infections (CROI 2009)
Coverage by HIV and Hepatitis.com - February 8 - 11, 2009, Montreal
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