- Data Indicate Pre-existing Lamivudine Resistance Predisposes Patients to
Higher Rates of BARACLUDE Resistance -
PRINCETON, N.J., March 24 /PRNewswire-FirstCall/ -- New BARACLUDE(R)
(entecavir) data presented today demonstrated a continued low incidence of
resistance in nucleoside-naive patients through five years of treatment. In
the nucleoside-naive chronic hepatitis B patients analyzed, no additional
patient developed resistance in the fifth year (n=108). Through five years
of treatment, the cumulative probability of developing mutations in the
virus that confer resistance to BARACLUDE (also called genotypic
resistance) was 1.2 percent. Bristol-Myers Squibb Company (NYSE: BMY)
announced the results at the 18th Conference of the Asia-Pacific
Association for the Study of the Liver (APASL) in Seoul, Korea.
In lamivudine-refractory patients who received BARACLUDE after
treatment with lamivudine failed, the cumulative probability of genotypic
BARACLUDE resistance was 51 percent through the fifth year. This finding is
consistent with prior observations that the pre-existence of
lamivudine-resistant mutations results in an increase in the rate of
BARACLUDE resistance.
"Many chronic hepatitis B patients require long-term treatment.
Unfortunately, the initial benefits of therapy can be lost after the
development of resistance. These five-year BARACLUDE data that demonstrate
long-term minimal resistance at 1.2 percent in nucleoside-naive patients
can be of great importance for patients," said Professor Ching-Lung Lai,
Chief, Division of Gastroenterology and Hepatology, University of Hong
Kong.
Drug resistance occurs when the hepatitis B virus (HBV) mutates,
thereby avoiding the effects of the medication. This can decrease the
efficacy of the current medication and may compromise future treatment
options. To date, studies have shown that multiple mutations are required
to develop BARACLUDE(R) (entecavir) resistance.
"These long-term BARACLUDE data continue to support the observations
seen in the first years of treatment and are reflective of BARACLUDE's high
genetic barrier to resistance," said Helena Brett-Smith, M.D., Group
Director of Clinical Research at Bristol-Myers Squibb. "More importantly,
we believe the data support BARACLUDE as an important initial treatment
choice for chronic hepatitis B, which is a disease that results in a large
global health burden."
About the Analysis
More than 700 patients across six studies initiated therapy on
BARACLUDE and were monitored for treatment response and resistance.
The year five analysis expands upon previous analyses, adding in
information on patients who received treatment with BARACLUDE during the
fifth year of follow-up (n=108 for patients in nucleoside-naive studies and
n=33 for patients in lamivudine-refractory studies).
In this comprehensive analysis, all patients enrolled in Bristol-Myers
Squibb clinical trials ETV-014, -015, -022, -027, -026 and -901 who
experienced a virologic breakthrough(1) or whose virus had not yet reached
undetectable levels(2) at weeks 48, 96, 144, 192, 240 or end of dosing,
were sequenced to determine if any changes occurred in the genetic code of
the virus that would result in resistance or loss of effectiveness of
BARACLUDE.
Nucleoside-naive patients in this analysis were initially treated with
BARACLUDE 0.5 mg in studies ETV-022 and -027 and continued treatment with
BARACLUDE 1 mg by enrolling in study ETV-901 with a treatment gap of less
than or equal to 35 days. Lamivudine-refractory patients in this analysis
initiated therapy on BARACLUDE 1 mg in studies ETV-014, -015, and -026 and
continued treatment in study ETV-901 with a treatment gap of less than or
equal to 35 days.
Viral load reduction in chronic hepatitis B patients treated with
BARACLUDE(R) (entecavir) in nucleoside-naive and lamivudine-refractory
studies was also evaluated.
Data Results
Results from these studies prior to this year five analysis were
previously announced on April 14, 2007.
Nucleoside-naive data
-- The incidence of BARACLUDE resistance in patients in
nucleoside-naive studies over time is low, with a cumulative
probability of genotypic BARACLUDE resistance of 1.2 percent
through five years.
-- No nucleoside-naive patient developed resistance (n=108) in year
five.
-- 93 percent of the nucleoside-naive patients taking BARACLUDE were
able to achieve and maintain an undetectable viral load
(HBV DNA <300 copies/mL) through year five (n=108).
Lamivudine-refractory data
-- The results in lamivudine-refractory patients in years one through
five were consistent with the finding that the pre-existence of
lamivudine-resistant substitutions resulted in an increase in the
emergence of BARACLUDE resistance, with a cumulative probability of
genotypic resistance of 51 percent through five years.
-- In year five, 43 percent of lamivudine-refractory patients had
virologic breakthrough with BARACLUDE resistance (n=33).
-- During this resistance monitoring program, 72 of the 187 lamivudine
refractory patients achieved undetectable viral load (<300 copies/mL)
and of these, three patients subsequently developed genotypic
resistance to BARACLUDE(R) (entecavir).
Indication and Important Safety Information About BARACLUDE(R)
(entecavir) 0.5 mg/1 mg Tablets
BARACLUDE(R) (entecavir) is a prescription medicine used for chronic
infection with hepatitis B virus (HBV) in adults where the virus is
multiplying and damaging the liver. BARACLUDE does not cure HBV or stop the
spread of HBV to others. People should not take BARACLUDE if they are
allergic to it or any of its ingredients. BARACLUDE has not been studied in
children and is not recommended for anyone less than 16 years of age.
People taking BARACLUDE should tell their healthcare provider right
away if they feel very weak or tired, have unusual muscle pain, have
trouble breathing, have stomach pain with nausea and vomiting, feel cold --
especially in their arms and legs, feel dizzy or lightheaded, or have a
fast or irregular heartbeat, as they may be signs of a serious condition
called lactic acidosis (buildup of an acid in the blood). Lactic acidosis
is a medical emergency and must be treated in the hospital. Some people who
have taken medicines like BARACLUDE have developed serious liver problems
called hepatotoxicity. This may occur with liver enlargement (hepatomegaly)
and fat in the liver (steatosis).
People should call their healthcare provider right away if they get any
of the following signs of liver problems: yellowing (jaundice) of the skin
or the white part of the eyes, darkening of the urine, lightening in the
color of bowel movements (stools), not feeling like eating food for several
days or longer, feeling sick to the stomach (nausea), or having lower
stomach pain. Lactic acidosis and hepatotoxicity have happened in some
people taking medicines like BARACLUDE.
For people taking BARACLUDE who have or get HIV (the virus that can
cause AIDS) and are not taking medicines for HIV at the same time, some HIV
treatments that they may take in the future may be less likely to work.
People are advised to get an HIV test before starting to take BARACLUDE and
anytime that there is a chance they were exposed to HIV. BARACLUDE will not
help HIV infection.
In some people, hepatitis B symptoms may get worse or become very
serious when they stop taking BARACLUDE. People should not stop BARACLUDE
without talking to their healthcare provider. Healthcare providers will
need to follow their patients and do blood tests to check the liver when
BARACLUDE is stopped. People should tell their healthcare provider if they
have or develop kidney problems because their healthcare provider may want
to do tests to see if a lower dose is needed.
Because BARACLUDE(R) (entecavir) is removed from the body through the
kidneys, a dose adjustment may be required. Healthcare providers may want
to perform tests to determine whether a patient needs a lower dose or
should take BARACLUDE less often than once a day.
It is not known if BARACLUDE is safe to use during pregnancy. It is not
known if BARACLUDE helps to prevent a pregnant mother from passing HBV to
her baby. A pregnant woman and her healthcare provider will need to decide
if BARACLUDE is right for her. A woman should not breastfeed if she is
taking BARACLUDE.
People should discuss with their healthcare provider all prescription
and non-prescription medicines, vitamins, herbal supplements, and other
health preparations they are taking or plan to take. BARACLUDE may interact
with medicines that leave the body through the kidneys. The safety and
effectiveness of BARACLUDE in liver transplant recipients is unknown. The
most common side effects of BARACLUDE in clinical studies were headache,
tiredness, dizziness, and nausea.
This list of side effects is not complete at this time because
BARACLUDE is still under study. People should report any new or continuing
symptom to their healthcare provider. BARACLUDE should be taken once daily
on an empty stomach (at least two hours after a meal and two hours before
the next meal). To learn more about BARACLUDE and for Full Prescribing
Information, including boxed WARNINGS, please visit http://www.bms.com/.
Bristol-Myers Squibb is a global biopharmaceutical and related health
care products company whose mission is to extend and enhance human life.
Visit Bristol-Myers Squibb at http://www.bms.com.
BARACLUDE(R) (entecavir) is a trademark of Bristol-Myers Squibb
Company. Full prescribing information for BARACLUDE, including boxed
WARNINGS, is available at http://www.bms.com/.
(1) Virologic breakthrough is defined as a greater than or equal to 1 log
increase in HBV DNA from nadir, as measured by the polymerase chai
reaction or PCR assay.
(2) Undetectable viral load is defined as HBV DNA levels less than 300
copies/mL, as measured by PCR assay.
SOURCE Bristol-Myers Squibb
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Related links:
http://www.bms.com
CONTACT:
Communications, Sonia Choi, +1-609-252-5132,
sonia.choi@bms.com, or Investor Relations, John Elicker,
+1-212-546-3775, john.elicker@bms.com, both of Bristol-Myers
Squibb
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