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BARACLUDE (entecavir) TWO-YEAR DATA ANALYSIS DID NOT DETECT EMERGENCE OF RESISTANCE IN NUCLEOSIDE-NAIVE CHRONIC HEPATITIS B PATIENTS
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Press release distributed this morning by Bristol-Myers Squibb
Additional Study Data Presented at AASLD Investigated BARACLUDE Treatment Through 96 Weeks in Nucleoside-Naive HBeAg Positive Patients
(SAN FRANCISCO, NOVEMBER 14, 2005)— Data planned for presentation at the 56th Annual Meeting of the American Association for the Study of Liver Diseases (AASLD) demonstrated no virologic rebounds due to resistance through two years in nucleoside-naive chronic hepatitis B adult patients (with wild-type virus) treated with the Bristol-Myers Squibb (NYSE: BMY) oral antiviral agent BARACLUDE (entecavir). Additional study data planned for presentation at AASLD showed significant increase in viral load suppression to undetectable levels compared to lamivudine in nucleoside-naive, chronic hepatitis B e-antigen (HBeAg) positive patients treated up to 96 weeks with BARACLUDE as part of a large-scale Phase III clinical trial (Study ETV-022).
"Data showed that 80 percent of patients taking BARACLUDE up to 96 weeks experienced cumulative confirmed viral load reductions to undetectable levels compared to 39 percent of patients taking lamivudine in Study ETV-022," said Robert Gish, M.D., a study investigator and medical director of the California Pacific Medical Center’s liver transplant program in San Francisco. "In patients treated for up to 96 weeks, treatment with BARACLUDE resulted in significant improvement compared to lamivudine as measured by reductions in viral load to undetectable levels and normalization of alanine aminotransferase (ALT) levels." Serious adverse events occurred in eight percent of patients in both the BARACLUDE and lamivudine treatment arms.
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BARACLUDE (entecavir) TWO-YEAR RESISTANCE DATA
Extended resistance monitoring for BARACLUDE in more than 650 nucleoside-naive, HBeAg-positive and HBeAg-negative chronic hepatitis B patients (with wild-type virus) showed no evidence of virologic rebound due to antiviral resistance to BARACLUDE following up to two years of treatment. BARACLUDE did not select for resistance substitutions (i.e., generate mutations) that reduced sensitivity to BARACLUDE or that are generally associated with lamivudine resistance (i.e., YMDD mutant). In lamivudine-refractory patients treated with BARACLUDE for two years, virologic rebounds that could be attributed to BARACLUDE resistance were observed in 9 percent (14/154) of patients. In all cases, patients who rebounded harbored specific resistance mutations attributed to previous lamivudine treatment.
BARACLUDE 96-WEEK DATA
Study ETV-022 evaluated 709 nucleoside-naive HBeAg-positive, chronic hepatitis B patients. Patients were randomized to receive 0.5 mg of BARACLUDE once daily (n=354) or lamivudine 100 mg once daily (n=355). Based on a patient’s virologic and serologic results at Week 48, a protocol-based decision was made at Week 52 regarding continuation or discontinuation of treatment. Patients defined as responders (HBV DNA <0.7 MEq/mL by bDNA and HBeAg loss) or non-responders (HBV DNA ≥0.7 MEq/mL by bDNA) discontinued treatment. Patients defined as virologic responders (HBV DNA <0.7 MEq/mL by bDNA but without HBeAg loss) continued blinded treatment for up to 96 weeks until they achieved response or had two sequential measurements of HBV DNA ≥0.7 MEq/mL during the second year of dosing.
Of patients who continued on BARACLUDE therapy after 48 weeks, there was a 17 percent increase in the number of subjects who became undetectable for HBV DNA (HBV DNA less than 300 copies/mL as measured by a common assay—polymerase chain reaction, or PCR). In contrast, no increase in the percentage of patients becoming undetectable for HBV DNA was seen after 48 weeks of therapy in patients taking lamivudine for up to 96 weeks. Normalization of ALT levels occurred in 79 percent of patients continuing BARACLUDE therapy after 48 weeks and 68 percent of lamivudine patients continuing therapy.
Cumulative confirmed endpoints were defined as two sequential measurements, or last on-treatment measurement, meeting the criterion. Eighty percent of patients taking BARACLUDE (entecavir) up to 96 weeks experienced cumulative confirmed viral load reductions to undetectable levels compared to 39 percent of patients taking lamivudine (p<0.0001). Thirty-one percent of patients taking BARACLUDE up to 96 weeks and through off-treatment follow up experienced a confirmed HBeAg seroconversion (HBeAg loss and gain of anti-HBe) compared to 26 percent of lamivudine patients [p=non-significant (NS)]. After six months of post-treatment follow-up, confirmed loss of hepatitis B surface antigen occurred in five percent of BARACLUDE and three percent of lamivudine patients experiencing up to 96 weeks of treatment (p=NS).
The cumulative on-treatment adverse event profiles for BARACLUDE and lamivudine through 96 weeks were comparable. Serious adverse events occurred in eight percent of patients in both treatment arms. Discontinuations due to adverse events occurred in less than one percent of BARACLUDE patients and three percent of lamivudine patients. Deaths occurred in two patients treated with BARACLUDE and four patients treated with lamivudine; none were related to study drug as determined by the clinical investigator. On-treatment ALT flares occurred in three percent of BARACLUDE and seven percent of lamivudine patients.
About BARACLUDE
Discovered at Bristol-Myers Squibb, BARACLUDE is a nucleoside analog, approved for marketing in the United States by the U.S. Food and Drug Administration (FDA) on March 29, 2005.
To date, BARACLUDE has also been approved in Macau, Brazil, Indonesia, Argentina, and Mexico. Bristol-Myers Squibb has submitted marketing applications for entecavir in other regions and countries around the world, including the EMEA, the Philippines, Malaysia, China, Taiwan, Singapore and Thailand.
The global BARACLUDE clinical trial program was the first to compare two antivirals, BARACLUDE and lamivudine (the most commonly used oral antiviral therapy for the treatment of chronic hepatitis B worldwide) and involved over 1,600 patients worldwide. Bristol-Myers Squibb is continuing to evaluate and monitor consenting chronic hepatitis B patients who participated in the BARACLUDE clinical trial program.
In the United States, Bristol-Myers Squibb offers a Patient Assistance Program (PAP) designed to provide access to BARACLUDE (entecavir) for patients who meet certain financial criteria and who either lack prescription coverage, are not eligible for Medicare or Medicaid or whose formularies do not cover BARACLUDE. Additional information on the PAP program is available by calling 800-272-4878.
Important Information About BARACLUDE (entecavir) 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 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.
Because BARACLUDE (entecavir) is removed from the body through the kidneys, a lower dose may be required. Healthcare providers may want to perform tests to determine whether a patient needs a lower dose.
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 breast-feed 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 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 (entecavir) and for Full Prescribing Information, including boxed WARNINGS, please visit 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. Visit Bristol-Myers Squibb on the World Wide Web at www.bms.com.
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