Entecavir (Baraclude) Produces Continued Clinical Benefits at 96 Weeks in Chronic
Hepatitis B Patients Resistant to Lamivudine (Epivir-HBV)s
By
Liz Highleyman  | Entecavir
(Baraclude) Tablet |
The
nucleoside analog entecavir (Baraclude) demonstrates
potent activity against hepatitis B virus (HBV),
but like other drugs in its class, there is concern that its long-term efficacy
may be limited by the emergence of drug resistance. In
2007, researchers reported that entecavir
was more effective than lamivudine (Epivir-HBV) in suppressing HBV viral load
over 96 weeks in chronic hepatitis B "e" antigen (HBeAg) positive patients
who had not received prior treatment. More recently, investigators presented data
at the 43rd
annual meeting of the European Association for the Study of the Liver (EASL)
in April showing that entecavir performed better than adefovir (Hepsera) over
96 weeks in treatment-naive HBeAg positive patients.
Now, in the July 2008
issue of Hepatology, an international team of researchers reports that
entecavir also beats lamivudine over 96 weeks
in "refractory" HBeAg positive patients who were previously treated
with lamivudine and experienced virological relapse, which often suggests emergence
of drug-resistant virus.
In
a double-blind controlled trial, the study authors previously found that switching
to 1 mg/day entecavir was superior to staying on 100 mg/day lamivudine over 48
weeks (this entecavir dose was higher than the 0.5 mg given to treatment-naive
patients in the studies mentioned above). Participants in the entecavir arm experienced
more histological improvement and alanine transaminase (ALT) normalization, as
well as greater virological response; 57% in the entecavir arm and 5% in the continued
lamivudine arm were classified as virological responders.
The investigators
continued to follow these patients with protocol-defined virological response
(HBV branched DNA < 0.7 MEq/mL, but still HBeAg positive). Of the 286 initially
randomized study participants, 77 patients in the entecavir arm continued on their
blinded therapy for up to 96 weeks. Patients were assessed for efficacy, safety,
and emerging resistance.
Results
•
Between week
48 and the end of dosing, the proportion of patients with HBV DNA < 300 copies/mL
by polymerase chain reaction increased from 21% to 40%.
•
ALT normalization
(< 1 x upper limit of normal) increased from 65% to 81%.
•
In the second
year, 10% achieved HBeAg seroconversion.
•
Of the 77 patients
in the second-year cohort, 6 developed entecavir resistance and 7 experienced
virological breakthrough (5 of whom had genotypic resistance acquired before year
2).
•
The safety
profile of entecavir in the second year was consistent with that reported during
year 1, with no serious or unexpected adverse events.
Based
on these findings, the study authors concluded, "Through 96 weeks of treatment,
1 mg entecavir resulted in continued clinical benefit in lamivudine-refractory
HBeAg positive chronic hepatitis B patients with a safety profile comparable to
lamivudine."
Toronto General Hospital, Toronto, Ontario, Canada; Ankara
University Medical School, Ankara, Turkey; Hacettepe University, Ankara, Turkey;
Hospital Universitario Austral, Pilar, Argentina; Chang Gung University and Memorial
Hospital, Taipei, Taiwan; Metropolitan Research, Fairfax, VA; University of Sao
Paulo, Sao Paulo, Brazil; ohn A. Burns School of Medicine, University of Hawaii,
Honolulu, HI; Bristol-Myers Squibb Company, Research & Development, Wallingford,
CT and Princeton, NJ.
7/04/08
Reference
M Sherman, C Yurdaydin,
H Simsek, and others. Entecavir therapy for lamivudine-refractory chronic hepatitis
B: Improved virologic, biochemical, and serology outcomes through 96 weeks. Hepatology
48(1):99-108. July 2008. [
Abstract
] |
| |
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