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 (