BARACLUDE(R) (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

WASHINGTON, May 21 /PRNewswire-FirstCall/ -- Bristol-Myers Squibb Company today announced new data from study ETV-079, which showed that treatment with BARACLUDE(R) (entecavir) demonstrated greater viral load reduction than adefovir at 48 weeks -- a result that was also seen at weeks 12 (primary endpoint) and 24. These data from an open-label, randomized viral kinetics study of 69 antiviral-naive chronic hepatitis B e-antigen (HBeAg) positive patients were presented at the annual Digestive Disease Week(R) meeting.

Study ETV-079 evaluated the antiviral activity of BARACLUDE and adefovir, and enrolled patients who had a high viral load at study entry (HBV DNA greater than or equal to 10(8) copies/mL). In this study, 58 percent of BARACLUDE-treated patients and 19 percent of adefovir-treated patients achieved undetectable viral load at 48 weeks.

"The study results show that BARACLUDE produced greater viral load reductions than adefovir at all time points analyzed -- from the earliest at 12 weeks to this latest analysis at 48 weeks," said Nancy Leung, M.D., of the Alice Ho Miu Ling Nethersole Hospital, Hong Kong, China.

The safety profile was comparable between the treatment groups. One patient treated with adefovir discontinued due to adverse events. 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 back pain, headache, influenza, nasopharyngitis, fever, upper respiratory tract infection, and urinary tract infection.

About the Study

Study ETV-079 was 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. Viral load reduction was also measured at weeks 24 and 48 of the follow-up. Patients received 0.5 mg of BARACLUDE(R) (entecavir) once daily (n=33) or 10 mg of adefovir once daily (n=32).

Patients in the BARACLUDE treatment group had a mean baseline viral load of 10.26 log(10) copies/mL. Patients in the adefovir treatment group had a mean baseline viral load of 9.88 log(10) copies/mL. Data Results

Week 48 * BARACLUDE-treated patients achieved a mean change in viral load of -7.28 log(10) copies/mL, and adefovir-treated patients achieved a mean change of -5.08 log(10) copies/mL (95 percent Confidence Interval -2.69, -1.03) * 58 percent of BARACLUDE-treated patients and 19 percent of adefovir- treated patients had undetectable viral load (HBV DNA <300 copies/mL, measured by a common assay -- polymerase chain reaction, or PCR) Week 24 * BARACLUDE-treated patients achieved a mean change in viral load of -6.97 log(10) copies/mL, and adefovir-treated patients achieved a mean change of -4.84 log(10) copies/mL (95 percent Confidence Interval -2.51, -1.20) * 45 percent of BARACLUDE-treated patients and 13 percent of adefovir- treated patients had undetectable viral load (HBV DNA <300 copies/mL) Week 12 * BARACLUDE-treated patients achieved a mean change in viral load of -6.23 log(10) copies/mL, and adefovir-treated patients achieved a mean change of -4.42 log(10) copies/mL (p < 0.0001) * 12 percent of BARACLUDE(R) (entecavir)-treated patients and 9 percent of adefovir-treated patients had undetectable viral load (HBV DNA <300 copies/mL) Adverse events in study ETV-079: * Seventy-eight percent (n=28/36) of patients taking BARACLUDE and 82 percent (n=27/33) of patients taking adefovir experienced an adverse event. The most common adverse events occurring in greater than 10 percent of patients in either treatment group were back pain, headache, influenza, nasopharyngitis, fever, upper respiratory tract infection, and urinary tract infection. * Six percent (n=2/36) of patients taking BARACLUDE and 15 percent (n=5/33) of patients taking adefovir experienced a Grade 3-4 adverse event. * Three percent (n=1/36) of patients taking BARACLUDE experienced a serious adverse event (elevated ALT that resolved with continued treatment). Nine percent (n=3/33) of patients taking adefovir experienced a serious adverse event (one patient had elevated ALT that resolved with continued treatment; one patient had acute hepatitis with ALT flare [ALT flare defined as greater than two times baseline and greater than 10 times the upper limit of normal]; one patient was involved in a motor vehicle accident). * There were no deaths in either arm and one patient discontinued treatment due to an adverse event. About BARACLUDE(R) (entecavir)

Discovered at Bristol-Myers Squibb, BARACLUDE(R) (entecavir) 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. BARACLUDE has been approved in more than 60 countries and regions around the world.

Important Information About BARACLUDE(R) (entecavir) 0.5mg/1mg 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(R) (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.

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 or a different dose schedule.

Because BARACLUDE is removed from the body through the kidneys, a lower dose or a different dose schedule 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(R) (entecavir) may interact with medicines that leave the body through the kidneys. 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(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/.