Healthcare Industry News: patient assistance program
News Release - May 23, 2006
96-Week Viral Suppression Data From Two Studies Presented for BARACLUDE(R) (entecavir) in Chronically-Infected Hepatitis B PatientsBARACLUDE and lamivudine (LVD) compared in nucleoside-naive hepatitis B e-antigen (HBeAg) negative patients (Study 027) and HBeAg-positive patients who were resistant to lamivudine (Study 026)
LOS ANGELES, May 23 (HSMN NewsFeed) -- Bristol-Myers Squibb Company (NYSE: BMY ) today presented 96-week clinical trial data at Digestive Disease Week from two Phase III studies demonstrating that BARACLUDEŽ (entecavir) led to a significant difference in viral load suppression to undetectable levels compared to lamivudine in two chronic hepatitis B patient types.
After up to 96-weeks of treatment, 94 percent of nucleoside-naive HBeAg-negative chronic hepatitis B patients treated with BARACLUDE experienced an undetectable viral load, defined as HBV DNA less than 300 copies per milliliter of blood (mL), compared to 77 percent of patients treated with lamivudine. This difference was statistically significant based on a cumulative analysis of all patients (p<0.0001). In addition, no evidence of BARACLUDE resistance was identified in these patients.
Additional 96-week study data presented today evaluated the use of BARACLUDE compared to continued lamivudine in lamivudine-refractory, HBeAg-positive chronic hepatitis B patients. After up to 96-weeks of treatment, 30 percent of patients who were switched to BARACLUDE treatment achieved an undetectable viral load, compared to less than 1 percent of patients who continued lamivudine treatment (p< 0.0001, based on cumulative analysis of all treated patients). Viral rebound due to BARACLUDE resistance occurred in 9 percent of patients through Week 96 and required the prior presence of LVD-resistance substitutions.
"It is increasingly recognized that hepatitis B viral load is an important evaluation tool for physicians when assessing, monitoring, and managing patients," said Morris Sherman, M.D., a BARACLUDE study investigator and associate professor of medicine at the University of Toronto.
Study ETV-027 was a large-scale, multinational, Phase III clinical trial of 638 HBeAg-negative chronic hepatitis B patients who had not previously received nucleoside treatment. In the study, patients received either BARACLUDE 0.5 mg once daily (n=325) or lamivudine 100 mg once daily (n=313) for a minimum of 52 weeks. At Week 52, patients were categorized into one of three groups based on evaluations at Week 48: non-responders (HBV DNA by branched DNA (bDNA) greater than or equal to 0.7 MEq/mL) who discontinued treatment; responders (HBV DNA by bDNA <0.7 MEq/mL and alanine aminotransferase (ALT) <1.25 times the upper limit of normal) who discontinued treatment and were followed for 24 weeks off-treatment; and virologic responders (HBV DNA by bDNA <0.7 MEq/mL and ALT greater than or equal to 1.25 x ULN) who went on to receive blinded treatment up to Week 96.
In a cumulative analysis of all patients treated through 96 weeks, 94 percent of patients in the BARACLUDE treatment group (n=325) experienced virologic suppression to undetectable levels, compared to 77 percent of patients given lamivudine (n=313) (p<0.0001). Additionally, the proportion of patients achieving or maintaining ALT level normalization was 89 percent for patients treated with BARACLUDE, compared to 84 percent of patients treated with lamivudine (p=0.05).
No evidence of BARACLUDE resistance was identified in patients treated for up to 96 weeks who had no prior lamivudine-resistance substitutions at baseline.
Safety was comparable between the treatment groups, with similar incidence of serious adverse events (6 percent with BARACLUDE, 8 percent with lamivudine) and any adverse event (76 percent with BARACLUDE, 80 percent with lamivudine). Discontinuations due to adverse events were observed in 2 percent of patients treated with BARACLUDE and 3 percent of patients treated with lamivudine. The incidence of ALT flares in patients treated with BARACLUDE on- or off-treatment were <1 percent and 8 percent, respectively, and in patients treated with lamivudine were 2 percent and 11 percent, respectively.
These 96-week results of Study ETV-027 are an update to the 48-week study results recently published in the March 9, 2006 issue of The New England Journal of Medicine.
As part of Study ETV-026, a multinational Phase III clinical trial, 286 lamivudine-refractory, HBeAg-positive chronic hepatitis B patients were randomized to receive BARACLUDE 1.0 mg once daily (n=141) or continued lamivudine 100 mg once daily (n=145) for a minimum of 52 weeks.
At Week 52, patients were categorized into one of three groups based on evaluations at Week 48: non-responders (HBV DNA by branched DNA larger than or equal to 0.7 MEq/mL) who discontinued treatment; responders (HBV DNA by bDNA <0.7 MEq/mL and HBeAg loss) who discontinued treatment and were followed for 24 weeks off-treatment; and virologic responders (HBV DNA by bDNA <0.7 MEq/mL and but HBeAg-positive) who went on to receive blinded treatment up to Week 96.
In a cumulative analysis of all patients treated through 96 weeks, 30 percent of patients treated with BARACLUDE (n=141) compared to less than 1 percent of patients who continued treatment with lamivudine (n=145) achieved an undetectable viral load. The difference was statistically significant (p<0.0001). Additionally, 17 percent of BARACLUDE patients compared to 6 percent of lamivudine patients experienced HBeAg seroconversion (p=0.0011). The proportion of patients achieving ALT normalization was significantly greater for patients treated with BARACLUDE (85 percent), compared to patients treated with lamivudine (29 percent) (p=0.0001).
Viral rebound due to BARACLUDE resistance mutations occurred in 9 percent of lamivudine-refractory patients during the second year of treatment.
Safety was comparable between the treatment groups, with similar incidence of serious adverse events (11 percent with BARACLUDE, 7 percent with lamivudine) and any adverse event (83 percent with BARACLUDE, 80 percent with lamivudine). Discontinuations due to adverse events were observed in 1 percent of patients treated with BARACLUDE versus 7 percent of patients treated with lamivudine. The incidence of ALT flares in patients treated with BARACLUDE on- or off-treatment were 1 percent and 12 percent, respectively, and in patients treated with lamivudine were 11 percent and 0 percent, respectively.
Discovered at Bristol-Myers Squibb, BARACLUDE is a nucleoside analogue approved for marketing in the United States by the U.S. Food and Drug Administration (FDA) on March 29, 2005. BARACLUDE is indicated for the treatment of chronic hepatitis B virus infection in adults with evidence of active viral replication with either evidence of serum aminotransferases (ALT or AST) or histologically active disease.
In addition to the U.S., BARACLUDE has been approved in more than 20 countries and regions around the world including Argentina, Brazil, China, Indonesia, Vietnam, Mexico, the Philippines and Singapore. Bristol-Myers Squibb has submitted marketing applications for entecavir in other regions and countries around the world, including the European Union.
The global BARACLUDE clinical trial program was the first large-scale Phase III program to compare two antivirals, BARACLUDE and lamivudine (the most commonly used oral antiviral therapy for the treatment of chronic hepatitis B worldwide) in the treatment of hepatitis B and involved more than 1,600 patients on five continents. Additional clinical studies investigating BARACLUDE use in more than 850 patients were conducted at five centers in China, where chronic hepatitis B is endemic. More than half of patients who took part in clinical trials for BARACLUDE were from China.
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 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 BARACLUDEŽ (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 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 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 http://www.bms.com.
About Digestive Disease Week
DDW is the largest international gathering of physicians, researchers and academics in the fields of gastroenterology, hepatology, endoscopy and gastrointestinal surgery. Jointly sponsored by the American Association for the Study of Liver Diseases, the American Gastroenterological Association, the American Society for Gastrointestinal Endoscopy and the Society for Surgery of the Alimentary Tract, DDW takes place May 20-25, 2006, at the Los Angeles Convention Center. The meeting showcases approximately 5,000 abstracts and hundreds of lectures on the latest advances in GI research, medicine and technology. For more information, visit http://www.ddw.org.
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 http://www.bms.com.
BARACLUDEŽ is a registered trademark of Bristol-Myers Squibb Company.
Full prescribing information for BARACLUDE is available at http://www.baraclude.com.
Source: Bristol-Myers Squibb
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