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91% OF BARACLUDE (ENTECAVIR) TREATED PATIENTS IN A FOUR-YEAR COHORT DEMONSTRATED VIROLOGIC SUPPRESSION TO UNDETECTABLE LEVELS
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In this Cohort of Nucleoside-Naive Chronic Hepatitis B e-Antigen (HBeAg) Positive Patients, Resistance Monitoring Identified One Patient with Genotypic Resistance to BARACLUDE
(BOSTON, Nov. 2, 2007) - Bristol-Myers Squibb Company (NYSE: BMY) today announced data from a four-year cohort (ETV-022/901, n=146), which showed that 91 percent (98/108) of patients treated with BARACLUDE (entecavir) suppressed the amount of hepatitis B virus in the blood, or viral load, to undetectable levels1 at week 192. Suppression of viral load to undetectable levels is a measure of antiviral treatment response; maintenance of viral load suppression is an important goal of chronic hepatitis B treatment. The results are being presented at the 58th Annual Meeting of the American Association for the Study of Liver Diseases (AASLD).
Patients in this cohort were nucleoside naive e-antigen (HBeAg)-positive patients with chronic hepatitis B infection. HBeAg is a viral protein identified as a marker of active replication of the hepatitis B virus. Patients in this cohort were initially treated with BARACLUDE 0.5 mg in study ETV-022 and continued treatment with BARACLUDE 1 mg by enrolling in study ETV-901 with a less than or equal to 35 day treatment gap.
Resistance monitoring in this cohort identified one patient with genotypic resistance to BARACLUDE at week 139 who had a virologic breakthrough at week 148.
"The data indicate that BARACLUDE maintained viral suppression through four years of treatment in this patient population," said Hugo Cheinquer, M.D., Universidade Federal Do Rio Grande Do Sul, Porto Alegre, Brazil. "That a majority of BARACLUDE patients had undetectable viral load at four years with one patient developing resistance is very encouraging news for physicians who treat this chronic disease."
1 HBV DNA levels less than 300 copies/mL by polymerase chain reaction (PCR) assay.
Safety events in this cohort were consistent with prior experience. Five deaths were reported in this cohort; no deaths were attributed to BARACLUDE (entecavir). Twelve percent of patients experienced a serious adverse event. The most common adverse events occurring in greater than or equal to 10 percent of patients were: upper respiratory tract infection (31 percent), headache (21 percent), cough (17 percent), diarrhea (16 percent), influenza (17 percent), nasopharyngitis (16 percent), pyrexia (12 percent) and upper abdominal pain (10 percent).
About the Nucleoside-Naive HBeAg-Positive Four-Year BARACLUDE Cohort (n=146)
This four-year cohort evaluated long-term efficacy and safety of BARACLUDE in nucleoside-naive chronic HBeAg-positive patients who received four years of continued BARACLUDE treatment. The four-year cohort consisted of 146 patients who met the following criteria:
- Enrolled in study ETV-022, which compared the efficacy and safety of BARACLUDE 0.5 mg versus lamivudine 100 mg in nucleoside-naive chronic HBeAg-positive patients
- Enrolled in study ETV-901, which evaluated the efficacy and safety of BARACLUDE 1 mg, after a treatment gap of less than or equal to 35 days
- Some patients initially received combination of BARACLUDE 1 mg and lamivudine 100 mg for a mean of 26 weeks in study ETV-901. The mean duration of BARACLUDE 1 mg monotherapy was 194 weeks
The analysis cohort was defined regardless of treatment response at the end of dosing in study ETV-022 or viral load, HBV serology, or ALT measurements at the start of dosing in study ETV-901. Serologic testing was conducted by a central laboratory in study ETV-022 and by local laboratories in study ETV-901.
Resistance was comprehensively monitored in the BARACLUDE clinical program. Patients with HBV DNA levels of greater than or equal to 300 copies/mL at weeks 48, 96, 144, 192, or at the end of dosing were genotyped and a phenotype was determined for all novel emerging substitutions. All patients experiencing a virologic breakthrough (greater than or equal to 1 log10 increase from nadir) were phenotyped even if they did not have emerging substitutions.
Study Results
• At week 192 of BARACLUDE (entecavir) treatment, 91 percent (n=98/108) of nucleoside-naive chronic HBeAg-positive patients in this cohort achieved undetectable viral load (HBV DNA <300 copies/mL) and 86 percent (n=96/112) of patients achieved ALT normalization (ALT ≦1 times the upper limit of normal).
• During years three and four, an additional 41 percent (n=39/96) of patients lost HBeAg and 16 percent (n=15/96) of patients achieved HBeAg seroconversion.
• Resistance monitoring in this cohort identified one patient with genotypic resistance to BARACLUDE who later experienced virologic breakthrough.
• Safety events were consistent with previous experience. Additional cumulative safety results of patients reported in this four-year cohort:
- Ninety percent of patients had any adverse event.
- Grade 3-4 adverse events were reported in 13 percent of patients.
- There were no discontinuations due to adverse events in this cohort.
- Less than one percent of patients experienced on-treatment ALT flares during the fourth year.
About BARACLUDE (entecavir)
Discovered at Bristol-Myers Squibb, BARACLUDE is a nucleoside analogue indicated for the treatment of chronic hepatitis B virus infection in adults with evidence of active viral replication with either evidence of persistent elevations in serum aminotransferases (ALT or AST) or histologically active disease. In addition to the United States, BARACLUDE has been approved in more than 60 countries and regions around the world.
Indication and Important Safety Information About BARACLUDE (entecavir) 0.5mg/1mg Tablets
BARACLUDE 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 (entecavir) 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 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 (entecavir) 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 pharmaceutical and related health care products company whose mission is to extend and enhance human life.
BARACLUDE (entecavir) is a trademark of Bristol-Myers Squibb Company.
Full prescribing information for BARACLUDE, including boxed WARNINGS, is available at http://www.bms.com/.
About Bristol-Myers Squibb
Bristol-Myers Squibb is a global pharmaceutical and related health care products company whose mission is to extend and enhance human life. Visit Bristol-Myers Squibb at www.bms.com.
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