Here’s the full Baraclude PR for archival purposes. It’s because of meta-analyses like this one that combination therapy is not (yet) considered a good idea in the treatment of HBV.
>> Three-Year Data Showed Low Incidence of BARACLUDE(R) (Entecavir) Resistance in Nucleoside-Naive Chronic Hepatitis B Patients
Monday October 30, 3:15 pm ET
Data Also Showed Higher Incidence of Resistance Over Three Years in Lamivudine-Refractory Patients
BOSTON, Oct. 30 /PRNewswire-FirstCall/ -- Bristol-Myers Squibb Company (NYSE: BMY ) today announced three-year results of the BARACLUDE® (entecavir) resistance monitoring program, which found the incidence of resistance to be low among patients treated with BARACLUDE in nucleoside-naive studies (n=673). Two patients, or less than one percent, experienced viral rebound due to BARACLUDE resistance through week 144. Study results also indicated a higher incidence of resistance in patients treated with BARACLUDE over three years in lamivudine-refractory studies. Viral rebound due to BARACLUDE resistance occurred in 15 percent (n=13/85) of patients in lamivudine-refractory studies during year three. Lamivudine resistance mutations are required for the development of BARACLUDE resistance. The study results were presented today at the 57th Annual Meeting of the American Association for the Study of Liver Diseases (AASLD).
Drug resistance occurs when a virus mutates to avoid the effects of the medication. This can make treatment of hepatitis B challenging because it can decrease the efficacy of the current medication and may compromise future treatment options. "Despite the fact that the hepatitis B virus is constantly changing, BARACLUDE creates a high barrier to resistance development in nucleoside-naive patients, as demonstrated by the less than one percent resistance rate through three years," said Richard Colonno, Ph.D., vice president for virology drug discovery at Bristol-Myers Squibb.
About the analysis
More than 700 patients across six studies initiated therapy on BARACLUDE and were monitored for treatment efficacy, safety and resistance.
The year three analysis evaluated those patients who received treatment with BARACLUDE® (entecavir) during the third year (n=152 for patients in nucleoside-naive studies and n=85 for patients in lamivudine-refractory studies). In this comprehensive analysis, all patients enrolled in Bristol- Myers Squibb clinical trials ETV-014, -015, -022, -027, -026 and -901 who experienced a virologic rebound (greater than or equal to one log increase in HBV DNA from nadir by PCR), or whose virus had not yet reached undetectable levels (by definition HBV DNA levels >300 copies/mL as measured by a common assay -- polymerase chain reaction, or PCR) at weeks 48, 96, 144 or end of dosing, as well as patients who discontinued treatment were sequenced to determine if any changes occurred in the genetic code of the virus that would result in resistance or loss of effectiveness of BARACLUDE.
Viral load reduction in chronic hepatitis B patients treated with BARACLUDE in nucleoside-naive and lamivudine-refractory studies was also evaluated.
Data results
The incidence of BARACLUDE resistance in patients in nucleoside-naive studies over time is low, with less than one percent of patients experiencing a viral rebound due to BARACLUDE resistance through week 144. BARACLUDE requires at least three different mutations to develop resistance.
-- Viral rebound due to BARACLUDE resistance (rtS202G) occurred in one patient out of 673 treated during the first year, who had lamivudine resistance (rtL180M and rtM204V/I) at the time of study entry and was initiated on 0.5 mg.
-- No additional viral rebounds due to BARACLUDE resistance were observed during the second year of treatment.
-- Viral rebound due to BARACLUDE resistance occurred in one additional patient out of 152 treated during the third year of treatment.
The emergence of resistance increased over three years in patients in lamivudine-refractory studies.
-- Viral rebound due to resistance occurred in one percent (2/192) of patients during the first year of treatment.
-- Viral rebound due to BARACLUDE resistance occurred in an additional nine percent (14/154) of patients during the second year of treatment.
-- Viral rebound due to BARACLUDE® (entecavir) resistance occurred in an additional 15 percent (13/85) of patients during the third year.
-- The results in these patients in years one through three were consistent with the finding that the presence of lamivudine-resistant substitutions resulted in an increase in the emergence of BARACLUDE resistance.
Of all BARACLUDE-treated patients with PCR measurements on treatment (intent-to-treat cumulative):
-- 94 percent of patients in nucleoside-naive studies achieved an undetectable viral load (<300 copies/mL) by the end of year three.
-- 40 percent of patients in lamivudine-refractory studies achieved an undetectable viral load (<300 copies/mL) by the end of year three.
About BARACLUDE
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 50 countries and regions around the world. <<
Here’s the Baraclude PR on 3-year efficacy based on follow-up of patients who remained e-positive at 2 years and met certain other conditions described below. As can be seen from these data, Baraclude is a fine drug.
>> BARACLUDE® (Entecavir) Demonstrated Viral Suppression to Undetectable Levels in Most Patients in a Three-Year Cohort
Monday October 30, 3:00 pm ET
90 Percent of Nucleoside-Naive Chronic Hepatitis B E-Antigen (HBeAg) Positive Patients in this Three-Year Cohort Achieved Undetectable Viral Load Levels at 144 Weeks
BOSTON, Oct. 30 /PRNewswire-FirstCall/ -- Bristol-Myers Squibb Company (NYSE: BMY ) today announced data from a three-year cohort (ETV-022/901, n=119), which showed BARACLUDE® (entecavir) suppressed viral load to undetectable levels in 90 percent of nucleoside-naive chronic hepatitis B e-antigen (HBeAg) positive patients at week 144 who continued on-treatment from week 96. In this cohort, undetectable HBV DNA levels were defined as less than 300 copies per mL of blood as measured by polymerase chain reaction (PCR). Suppression of viral load to undetectable levels is one of several measures of antiviral treatment response; a sustained, undetectable viral load is an important goal of chronic hepatitis B treatment. The results of this three-year cohort were presented today at the 57th Annual Meeting of the American Association for the Study of Liver Diseases (AASLD).
"The response of most patients in this cohort to undetectable levels of viral load at three years is encouraging and these data provide important information about BARACLUDE for healthcare professionals," said Hugo Cheinquer, M.D., Universidade Federal Do Rio Grande Do Sul, Porto Alegre, Brazil.
Patients in this cohort had previously been treated for 96 weeks in the BARACLUDE arm of study ETV-022, which compared the efficacy and safety of 0.5 mg of BARACLUDE vs. lamivudine in nucleoside-naive chronic HBeAg-positive patients. In this three-year cohort of patients, normalization of alanine aminotransferase (ALT) was noted in 80 percent of patients at week 144 of BARACLUDE treatment. All patients in this cohort were HBeAg-positive at the end of their treatment in study ETV-022[i.e. this was an entry requirement for the third year]: 33 percent of them lost HBeAg and 16 percent achieved HBeAg seroconversion by week 144. Serologic testing was conducted by a central laboratory up to week 96 and by local laboratories in the third year.
Safety events were consistent with prior experience. During the third year of treatment in this cohort, eight percent of patients experienced a serious adverse event and 89 percent of patients had any adverse event in the third year. Grade 3-4 adverse events were reported in 11 percent of patients at week 144. There were no discontinuations due to adverse events in this cohort during this third year of treatment. The most common adverse events occurring in greater than or equal to 10 percent of patients were: upper respiratory tract infection (30 percent), headache (22 percent), cough (18 percent), diarrhea (18 percent), influenza (16 percent), nasopharyngitis (14 percent) and upper abdominal pain (10 percent). Two patients in this cohort died, but these deaths were not attributed to BARACLUDE® (entecavir). No patients experienced on-treatment ALT flares during the third year.
About the Nucleoside-Naive HBeAg-Positive Three-Year BARACLUDE Cohort
This cohort evaluated the long-term efficacy and safety of BARACLUDE in nucleoside-naive chronic HBeAg-positive patients who received three years of BARACLUDE treatment. The three-year cohort consisted of 119 patients who met the following criteria:
* Completed study ETV-022, and at 96 weeks had HBV DNA < 0.7 MEq/mL and remained HBeAg-positive
* Completed study ETV-022 and enrolled in study ETV-901 without an intervening gap greater than 35 days
* Had HBV DNA tested by PCR at week 144
Data results of the three-year cohort
* At week 144, 90 percent (n=107/119) of nucleoside-naive chronic HBeAg-positive patients in this cohort achieved undetectable viral load (HBV DNA <300 copies/mL) and 80 percent (n=95/119) of patients achieved ALT normalization (ALT less than or equal to 1 times the upper limit of normal) at week 144 of BARACLUDE treatment.
* By week 144, 33 percent (n=35/106) of patients lost HBeAg and 16 percent (n=17/105) of patients achieved HBeAg seroconversion by week 144. <<
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