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BARACLUDE (ENTECAVIR) TREATMENT RESULTED IN GREATER VIRAL LOAD SUPPRESSION COMPARED TO ADEFOVIR AT 96 WEEKS IN ANTIVIRAL-NAìVE ADULT CHRONIC HEPATITIS B E-ANTIGEN POSITIVE PATIENTS
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Press announcement from Bristol-Myers Squibb.
(MILAN, Italy, April 26, 2008) - Bristol-Myers Squibb Company (NYSE:BMY) today announced new data from the E.A.R.L.Y. study (ETV-079), in which treatment of antiviral-naive adult chronic hepatitis B patients with BARACLUDE (entecavir) resulted in greater long-term viral load reduction than adefovir at 96 weeks Ñ consistent with earlier 12-week results (primary endpoint). Suppression of viral load to undetectable levels is a measure of antiviral treatment response and is an important goal of chronic hepatitis B treatment. These data were presented today in Milan, Italy, at the 43rd Annual Meeting of the European Association for the Study of the Liver (EASL).
The E.A.R.L.Y. study is an open-label, randomized, viral kinetics study of 69 antiviral-naive chronic hepatitis B e-antigen (HBeAg) positive patients, comparing the antiviral activity of BARACLUDE and adefovir. All patients in this study had a high viral load at study entry.1 Of the 49 patients who remained in the study at 96 weeks, 79 percent (n=23/29) of BARACLUDE-treated patients and 50 percent (n=10/20) of adefovir-treated patients achieved undetectable viral load.2 The mean reduction in viral load from baseline in patients treated with BARACLUDE was -7.82 log10 copies/mL and was -5.96 log10 copies/mL in patients treated with adefovir at week 96.
"BARACLUDE maintains considerable antiviral efficacy through two years of treatment in this analysis," said Nancy Leung, M.D., of the Alice Ho Miu Ling Nethersole Hospital, Hong Kong, China. "This is important information for health care providers to consider when evaluating initial treatment options to suppress viral load in antiviral-naive chronic hepatitis B patients."
1 Patients were required to have a screening viral load of greater than or equal to 108 copies/mL at study entry.
2 In this study, undetectable viral load was defined as HBV DNA less than 300 copies/mL, measured by PCR assay.
The safety profile was comparable between the treatment groups through 96 weeks. Three percent of patients receiving BARACLUDE (entecavir) (n=1) and 12 percent of patients receiving adefovir (n=5) experienced a serious adverse event. No deaths were observed in either treatment group. The most common adverse events occurring in greater than 10 percent of patients in either treatment group were headache, nasopharyngitis, upper respiratory tract infection, influenza, pyrexia, urinary tract infection, cough, back pain, and diarrhea.
Data Results
By week 96, 22 of the 69 enrolled patients had discontinued the study. Of these, two patients receiving adefovir discontinued due to investigator-determined lack of treatment efficacy between the beginning of year two dosing and the 96-week analysis. The 96-week data reported below represent the results of the 49 patients who entered year two dosing (29 BARACLUDE-treated patients and 20 adefovir-treated patients), using the non-completer = failure (NC=F) method of analysis.
Week 96
· BARACLUDE-treated patients achieved a mean change in viral load of -7.82 log10 copies/mL from baseline, and adefovir-treated patients achieved a mean change of -5.96 log10 copies/mL.
· 79 percent (n=23/29) of BARACLUDE-treated patients and 50 percent (n=10/20) of adefovir-treated patients had undetectable viral load (HBV DNA less than 300 copies/mL, measured by the polymerase chain reaction or PCR assay).
· No BARACLUDE-treated patient (n=0/29) and 35 percent (n=7/20) of adefovir-treated patients had viral load greater than or equal to 105 copies/mL.
· 97 percent (n=28/29) of BARACLUDE patients achieved ALT normalization (ALT of less than or equal one time the upper limit of normal) compared with 85 percent (n=17/20) of adefovir-treated patients.
· 24 percent (n=7/29) BARACLUDE-treated patients achieved HBe seroconversion compared with 25 percent (n=5/20) adefovir-treated patients.
· Six BARACLUDE (entecavir)-treated patients and 16 adefovir-treated patients discontinued therapy prior to week 96.
· No BARACLUDE-treated patients and one adefovir-treated patient discontinued due to adverse events.
· No BARACLUDE-treated patients and six adefovir-treated patients discontinued due to investigator-determined treatment failure or lack of efficacy.
· Three BARACLUDE-treated patients and four adefovir-treated patients met the treatment response criteria at 52 weeks and entered a 24- or 48-week off-treatment follow-up monitoring phase.
· Two BARACLUDE-treated patients and one adefovir-treated patient were lost to follow-up, one BARACLUDE-treated patient was non-compliant, two adefovir-treated patients withdrew consent, one adefovir-treated patient became pregnant, and one adefovir-randomized patient was treated with BARACLUDE.
Week 12 (primary endpoint)
· BARACLUDE-treated patients achieved a mean change in viral load of -6.23 log10 copies/mL from baseline, compared to adefovir-treated patients who achieved a mean change of -4.42 log10 copies/mL (p < 0.0001).
· 12 percent of BARACLUDE-treated patients and 9 percent of adefovir-treated patients had undetectable viral load (HBV DNA <300 copies/mL).
Additional Cumulative Safety Results of the E.A.R.L.Y. Study at 96 Weeks
· 83 percent of patients in the BARACLUDE arm (n=30) and 82 percent of patients in the adefovir arm (n=27) experienced any adverse event.
· Eight percent of patients receiving BARACLUDE (n=3) and 15 percent of patients receiving adefovir (n=5) experienced any Grade 3-4 adverse event.
· Three percent of patients receiving BARACLUDE (n=1) and 12 percent of patients receiving adefovir (n=5) experienced a serious adverse event.
· No deaths were observed in either treatment group.
· No patients in the BARACLUDE arm and one patient in the adefovir arm experienced an ALT flare (defined as ALT greater than two times baseline and greater than 10 times the upper limit of normal).
About the Study
The E.A.R.L.Y. study (ETV-079) is a randomized, open-label, comparative viral kinetics study of antiviral-naive chronic HBeAg-positive patients evaluating antiviral activity as measured by mean reduction in viral load, or levels of hepatitis B virus (HBV DNA) in the blood. HBeAg or e-antigen, is a viral protein associated with hepatitis B infections, and is found in the blood only when there is virus present.
The primary endpoint for the study was mean reduction in HBV DNA levels at week 12. The secondary endpoints included the mean change in viral load from baseline through week 96, the proportion of patients in each treatment group who achieved ALT normalization, HBeAg loss and HBe seroconversion, and safety.
Sixty-nine patients were randomized in the study and of these, 65 completed the first 12 weeks. Patients in this study received either 0.5 mg of BARACLUDE (entecavir) once daily (n=33) or 10 mg of adefovir once daily (n=32) for a minimum of 52 weeks. Patients in the BARACLUDE treatment group had a mean baseline viral load of 10.26 log10 copies/mL. Patients in the adefovir treatment group had a mean baseline viral load of 9.88 log10 copies/mL.
According to study protocol, patients who achieved a treatment response at 52 weeks discontinued treatment and entered a follow-up monitoring phase. Three BARACLUDE-treated patients and four adefovir-treated patients met this criterion and entered the follow-up monitoring phase lasting up to 48 weeks. Patients who did not achieve a treatment response at 52 weeks continued on study to 96 weeks. Treatment response in this study is defined as HBeAg seroconversion and viral load less than 104 copies/mL for 24 weeks, with undetectable viral load at the end of the 24-week period.
Indication and Important Safety Information About BARACLUDE¨ (entecavir) 0.5 mg/ 1 mg Tablets
BARACLUDE (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 (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 (entecavir) 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 www.bms.com.
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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
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