Treatment
with Entecavir Produces Greater Viral Load Reduction Compared to Adefovir at 48
Weeks in HBeAg-positive Patients By
Ronald Baker, PhD
Elevated HBV DNA is associated with increased
risk of liver disease progression and complications in patients with chronic
hepatitis B. The aim of antiviral therapy, therefore, is to rapidly and profoundly
reduce HBV DNA levels.
 | Baraclude
Tablet |
Discovered
at Bristol-Myers Squibb, entecavir
(Baraclude) is an FDA-approved nucleoside analogue indicated for the treatment
of chronic hepatitis B virus (HBV) infection in adults with evidence of active
viral replication with either persistent elevations in serum aminotransferases
(ALT or AST) or histologically active disease. Entecavir
has been approved for use in chronic hepatitis B patients in more than 60 countries
around the world.
 | Hepsera
Tablet |
In
a poster presentation at Digestive Disease Week (DDW 2007)
in Washington, DC this week, researchers released 48-week results from a randomized,
open-label, comparative study comparing entecavir to adefovir
(Hepsera) in HBeAg+ chronic hepatitis B patients. HBeAg, or "e"
antigen, is a viral protein that is found in the blood only when there is virus
present.
The study (ETV-079) was conducted at medical facilities in China
(Hong Kong), Canada (Toronto), Taiwan, the Philippines, Indonesia, and the U.S.
(Miami, Philadelphia, and at the BMS Research Institute in Wallingford, CT).
The
primary objective of the ETV-079 study was to assess whether entecavir has superior
early antiviral efficacy compared with adefovir, as measured by the mean reduction
in serum HBV DNA levels using the Roche Amplicor Assay (log10 copies/mL) at Week
12.
The secondary objective was to describe the following:
•
HBV kinetics through
Week 12;
•
Mean HBV DNA change
from baseline through Week 48;
•
Proportions of patients
in each treatment group who achieved HBV DNA < 300 copies/mL;
•
HBeAg loss and HBe
seroconversion;
•
Safety data
A
total of 69 HBeAg+, antiviral treatment-naive chronic hepatitis B patients were
randomized 1:1 to receive either entecavir (0.5 mg) or adefovir (10 mg) once daily
for a minimum of 52 weeks. Mean baseline HBV DNA was 10.26 log10 in the entecavir
arm and 9.88 log10 copies/mL in the adefovir arm. Measurements of serum HBV DNA
were obtained through Week 12 and at Weeks 24, 36, and 48. The
sample size of at least 26 randomized subjects per arm provided 90% power to demonstrate
superiority in mean HBV DNA reduction from baseline at Week 12. HBV
serology and safety laboratory testing were also performed. Evaluable patients
were those who had baseline and Week-12 HBV DNA by PCR and received their assigned
treatment. The
treatment difference in reduction of HBV DNA at Week 48 was based on a linear
regression model adjusted for baseline levels. Results •
Entecavir demonstrated
superior early antiviral activity and viral kinetic profiles compared to adefovir
as early as Day 10, with superior reduction in HBV DNA at Week 12 (-6.23 vs -4.42
log10 copies/mL; P < 0.0001).
•
The mean HBV DNA change
from baseline at Week 48 was -7.28 log10 in the entecavir arm vs -5.08 log10 copies/mL
in the adefovir arm (a difference of -1.86].
•
At Week 48, 19 entecavir-treated
patients (58%) vs 6 adefovir-treated patients (19%) achieved undetectable HBV
DNA (< 300 copies/mL) by PCR.
•
25 entecavir-treated
patients (76%) vs 20 adefovir-treated patients (63%) achieved ALT ? 1 x ULN.
•
5 entecavir-treated
patients (15%) vs 7 adefovir-treated patients (22%) achieved HBe seroconversion.
•
78% of patients taking
entecavir (28 of 36) and 82% taking adefovir percent (27 of 33) experienced an
adverse event.
•
The most common adverse
events occurring in greater than 10% of patients in either treatment group were
back pain, headache, influenza, nasopharyngitis, fever, upper respiratory tract
infection, and urinary tract infection.
•
6% of patients taking
entecavir (2 of 36) and 15% taking adefovir (5 of 33) experienced a Grade 3-4
adverse event.
•
3% of patients taking
entecavir (1 of 36) experienced a serious adverse event (elevated ALT that resolved
with continued treatment).
•
9% of patients taking
adefovir (3 of 33) experienced a serious adverse event (1 had elevated ALT that
resolved with continued treatment; 1 had acute hepatitis with ALT flare [defined
as greater than 2 x baseline and greater than 10 x ULN]; 1 was involved in a motor
vehicle accident).
•
No patients in either
arm discontinued due to adverse events.
Conclusion In
conclusion, the investigators wrote, "At Week 48, entecavir was observed
to result in a greater decrease from baseline in HBV DNA than adefovir (7.28 vs
5.08 log10 copies/mL), with 58% of entecavir-treated patients achieving undetectable
HBV DNA compared to 19% of adefovir-treated patients." They added that, "Entecavir
was well tolerated." Alice
Ho Miu Ling Nethersole Hospital, Taipo, Hong Kong SAR, China; Toronto General
Hospital, Toronto, ON, Canada; China Medical University Hospital, Taichung, Taiwan;
University of Santo Tomas, Manila, Philippines; University of Indonesia, Jakarta,
Indonesia; The University of Hong Kong, China; Miller School of Medicine, Miami,
FL; Thomas Jefferson University Hospital, Philadelphia, PA; Bristol-Myers Squibb
Pharmaceutical Research Institute, Wallingford, CT.
05/25/07
Sources
N Leung , M Sherman, C-Y Peng, and others. Entecavir (ETV) Results in Higher
HBV- DNA Reduction vs Adefovir (ADV) in Chronically Infected HBeAg+ Antiviral-Naive
Adults: 48-Week Results (E.A.R.L.Y. Study). Digestive Disease Week 2007 (DDW 2007).
Washington, DC. May 19-24, 2007. Abstract S-1773.
Bristol-Myers Squibb.
Baraclude (entecavir) treatment demonstrated greater viral load reduction compared
to adefovir at 48 weeks in study of antiviral-naive chronic hepatitis B e-antigen
Positive Patients. Press Release. May 21, 2007. <----
DDW 2007 Main Page
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