Bristol-Myers Squibb Company
(NYSE: BMY) today announced three-year results of the BARACLUDE(R)
(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(R) (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(R) (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 (