Biotech Values

[DewDiligence]

Here’s one more EASL PR. It’s about
Baraclude’s 4-year resistance profile;
it should be read in conjunction with
#msg-14399529, which contains the
corresponding 3-year data from 2006
AASLD. The fact that prior Lamivudine
treatment raises resistance to Baraclude
is one of the reasons that dual nucleoside
treatment for HBV has not been considered
a good idea.

http://biz.yahoo.com/prnews/070414/nysa001.html?.v=82

>>
Four-Year Data Demonstrate Continued Low Incidence of BARACLUDE (entecavir) Resistance in Nucleoside-naive Chronic Hepatitis B Patients

Saturday April 14, 10:45 am ET

Higher Rates of BARACLUDE Resistance Seen in Lamivudine-Refractory Patients

PRINCETON, N.J., April 14 /PRNewswire-FirstCall/ -- Bristol-Myers Squibb Company (NYSE: BMY ) today announced new results of the BARACLUDE® (entecavir) resistance monitoring program, which found a continued low incidence of resistance in studies of nucleoside-naive chronic hepatitis B patients through four years of treatment (n=663). In the three nucleoside-naive studies analyzed, two patients, or less than one percent, experienced virologic breakthrough due to BARACLUDE resistance through the third year, and no additional patients developed resistance in the fourth year. In lamivudine-refractory patients, virologic breakthrough due to BARACLUDE resistance occurred in 15 percent (n=8/53) of patients during year four. The study results were presented today at the 42nd Annual Meeting of the European Association for the Study of Liver Diseases (EASL) in Barcelona, Spain.

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. To date, studies have shown that multiple mutations are required to develop BARACLUDE resistance.

"The low incidence of resistance seen in nucleoside-naive patients through four years of treatment reflects BARACLUDE's high barrier to resistance in this patient population," 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® (entecavir) and were monitored for treatment response and resistance.

The year four analysis evaluated those patients who received treatment with BARACLUDE during the fourth year (n=120 for patients in nucleoside-naive studies and n=53 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 breakthrough (greater than or equal to one log increase in HBV DNA from nadir as measured by a common assay - polymerase chain reaction or PCR), or whose virus had not yet reached undetectable levels - a measurement of the levels of hepatitis B virus in the blood (HBV DNA levels >300 copies/mL by PCR assay) at weeks 48, 96, 144, 192 or end of dosing 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 virologic breakthrough due to BARACLUDE resistance through four years.

-- Virologic breakthrough due to BARACLUDE resistance (rtS202G) occurred in one patient out of 663 treated during the first year, who had lamivudine resistance (rtM204I) at the time of study entry and was initiated on 0.5 mg.

-- No additional virologic breakthroughs due to BARACLUDE resistance were observed during the second year of treatment. One patient was identified with emerging BARACLUDE resistance without virologic breakthrough in year two; this patient did not continue into year three.

-- Virologic breakthrough due to BARACLUDE® (entecavir) resistance occurred in one additional patient out of 149 treated during the third year of treatment.

-- No additional virologic breakthroughs due to BARACLUDE resistance were observed during the fourth year of treatment.

The emergence of resistance increased over four years in patients in lamivudine-refractory studies.

-- Virologic breakthrough due to resistance occurred in one percent (2/187) of patients during the first year of treatment.

-- Virologic breakthrough due to BARACLUDE resistance occurred in an additional ten percent (14/146) of patients during the second year of treatment.

-- Virologic breakthrough due to BARACLUDE resistance occurred in an additional 16 percent (13/80) of patients during the third year.

-- Virologic breakthrough due to BARACLUDE resistance occurred in an additional 15 percent (8/53) of patients during the fourth year.

-- The results in these patients in years one through four were consistent with the finding that the pre-existence of lamivudine-resistant substitutions resulted in an increase in the emergence of BARACLUDE resistance.
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