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发表于 2003-11-27 17:26
[B]Gilead Announces Preliminary Results from 48-Week Phase III Study of
Emtricitabine in Patients with Chronic Hepatitis B[/B]
Foster City, CA, November 25, 2003 - Gilead Sciences, Inc. (Nasdaq:
GILD) today announced preliminary results from a Phase III clinical
trial (Study FTCB-301) comparing the efficacy and safety of
emtricitabine 200 mg once daily versus placebo in patients with
chronic hepatitis B. Preliminary results from this analysis
demonstrate that treatment with emtricitabine 200 mg once daily for
48 weeks is associated with improvements in liver histology in 62
percent of patients who received the drug compared to 25 percent of
patients who received placebo (p<0.001). Improvement in liver
histology is an important marker of treatment benefit in patients
with chronic hepatitis B, and the primary endpoint in this study.
Gilead expects to present these data in detail at a scientific
conference next year.
"Gilead is dedicated to the development and marketing of
therapeutics to address the challenges in treating chronic hepatitis
B, which remains under-diagnosed and significantly under-treated,"
said John C. Martin, PhD, President and CEO of Gilead
Sciences. "With the data from the first large study of emtricitabine
in hepatitis B now in hand, Gilead will continue to evaluate the
development path for this compound moving forward."
Study Design
Study FTCB-301 is a 48-week, double-blind, placebo-controlled
clinical trial conducted at 34 sites in seven countries in North
America, Europe and Asia. The trial was designed to compare the
efficacy and safety of emtricitabine 200 mg once daily versus
placebo in 248 patients with chronic hepatitis B who had not
previously received therapy with a nucleoside analogue. Patients
were randomized (2:1) to receive emtricitabine 200 mg once daily or
placebo for 48 weeks. Prior to study entry, all patients were
hepatitis B surface ("s") antigen positive for at least six months.
Both hepatitis B "e" antigen negative and hepatitis B "e" antigen
positive patients were enrolled in the study. At study entry,
patients were required to have elevated levels of the liver enzyme
alanine aminotransferase (ALT) and detectable serum levels of HBV
DNA.
Study Results
After 48 weeks, 62 percent of patients treated with emtricitabine
200 mg once daily exhibited significant improvements in liver
histology, compared with 25 percent of patients receiving placebo
(p<0.001). Improvement in liver histology is defined as a reduction
from baseline of two points or more in the histological activity
index (HAI) score and absence of progression in liver fibrosis using
the Knodell scoring system.
Study FTCB-301 also examined changes after 48 weeks in HBV DNA
(Digene Hybrid Capture II Assay), ALT levels, genotype mutations and
serology. At baseline, emtricitabine and placebo patients had,
respectively, median HBV DNA levels of 7.67 log10 copies/mL and 7.42
log10 copies/mL and median ALT of 81 IU/L and 92 IU/L. Treatment
with emtricitabine resulted in a median reduction in HBV DNA from
baseline of 3.00 log10 copies/mL compared with a median reduction in
the placebo group of 0.44 log10 copies/mL (p<0.001). After 48 weeks,
56 percent of emtricitabine patients had HBV DNA below the assay
lower limit of detection (4700 copies/mL) compared to seven percent
in the placebo arm (p<0.001). Of the patients randomized to the
emtricitabine arm of the study, 13 percent had virus with the YMDD
mutation at week 48. The YMDD mutation in the HBV polymerase gene is
known to confer resistance to emtricitabine and lamivudine.
Additionally, patients treated with emtricitabine achieved a median
ALT reduction of 52 IU/L, compared to a median ALT reduction of 25
IU/L for patients receiving placebo (p<0.001). In the subset of
patients who were HBeAg-positive at baseline there was no
significant difference between the treatment and placebo arms in the
percentage of patients that achieved seroconversion, which is
defined as both the disappearance of the hepatitis B "e" antigen
(HBe-antigen negative) and the appearance of antibodies specific for
this antigen (HBe-antibody positive).
Through 48 weeks, the discontinuation rate was similar between the
treatment and placebo arms, with five percent of patients receiving
emtricitabine and seven percent receiving placebo discontinuing from
study. The most common adverse events were influenza, upper
respiratory infection, headache, fatigue, abdominal pain, post-
procedural pain (associated with liver biopsy) and cough.
Additionally, there were no significant differences in the incidence
of adverse events and grade 3 and 4 laboratory abnormalities between
either arm of the study, with the exception of elevated ALT levels,
which occurred more frequently in the placebo group.
Emtricitabine
Emtricitabine is a nucleoside analogue reverse transcriptase
inhibitor. It works by blocking reverse transcriptase, an enzyme
involved in the replication of HBV in the body. In addition to
studies in patients with chronic hepatitis B, emtricitabine has been
studied in patients with HIV. Approved in 2003, emtricitabine is
marketed as EmtrivaT for use in combination with other
antiretrovirals for the treatment of HIV infection in the United
States and Europe.
In HIV clinical studies, more than 2000 HIV-infected adults have
been treated with Emtriva for periods of 10 days to 200 weeks in
Phase I, II and III clinical trials. Assessment of adverse events
(without regard to relationship to study drug) is based on pooled
data from two Phase III studies in which 571 treatment-naïve and
440
treatment-experienced patients received Emtriva (n=580) or a
comparator drug (n=431) for 48 weeks. The most common adverse events
that occurred in patients receiving Emtriva were headache, diarrhea,
nausea and rash, which were generally of mild to moderate severity.
Approximately one percent of patients discontinued participation in
the clinical studies due to these events. All adverse events were
reported with similar frequency in Emtriva and control treatment
groups with the exception of skin discoloration, which was reported
with higher frequency in the Emtriva treated group. Skin
discoloration, manifested by hyperpigmentation (excess pigmentation)
on the palms and/or soles, was generally mild and asymptomatic. The
mechanism and clinical significance of this adverse event are
unknown. Lactic acidosis and severe hepatomegaly with steatosis,
including fatal cases, have been reported with the use of nucleoside
analogues alone or in combination with other antiretrovirals.
Chronic Hepatitis B
Hepatitis B is a serious disease that attacks the liver and can
cause chronic (lifelong) infection, cirrhosis of the liver, liver
cancer and death in up to a third of patients. Worldwide, there are
approximately 400 million people with chronic hepatitis B, of which
approximately one million people will die this year from
complications from the disease, making chronic hepatitis B one of
the 10 most common causes of death. Gilead currently markets
Hepsera® (adefovir dipivoxil 10 mg) for the treatment of chronic
HBV
infection in both the United States and Europe. In April 2002,
Gilead signed a licensing agreement with GlaxoSmithKline (GSK),
granting GSK rights to commercialize Hepsera in Asia, Latin America
and other territories.
About Gilead
Gilead Sciences is a biopharmaceutical company that discovers,
develops and commercializes therapeutics to advance the care of
patients suffering from life-threatening diseases worldwide. The
company has seven marketed products and focuses its research and
clinical programs on anti-infectives. Headquartered in Foster City,
CA, Gilead has operations in the United States, Europe and Australia.
This press release includes forward-looking statements, within the
meaning of the Private Securities Litigation Reform Act of 1995,
that are subject to risks, uncertainties and other factors that
could cause actual results to differ materially from those referred
to in the forward-looking statements. Such risks and uncertainties
include the risk that these 48-week data will not be observed
through longer treatment periods. The reader is cautioned not to
rely on these forward-looking statements. These and other risks are
described in detail in the Gilead Annual Report on Form 10-K for the
year ended December 31, 2002 and in Gilead's Quarterly Reports on
Form 10-Q, all of which are on file with the U.S. Securities and
Exchange Commission. All forward-looking statements are based on
information currently available to Gilead and Gilead assumes no
obligation to update any such forward-looking statements. |
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