Bristol-Myers Squibb Company (NYSE:BMY) and Gilead Sciences, Inc.
(Nasdaq:GILD) today announced an agreement to commercialize
ATRIPLA(TM) (efavirenz 600 mg/ emtricitabine 200 mg/ tenofovir
disoproxil fumarate 300 mg) in Canada for the treatment of HIV-1
infection in adults, subject to the approval of the product by Health
Canada. ATRIPLA is the first once-daily single tablet regimen (STR)
for HIV intended as a stand-alone therapy or in combination with other
antiretrovirals. ATRIPLA received approval from the U.S. Food & Drug
Administration on July 12, 2006.
The agreement is the result of negotiations between Bristol-Myers
Squibb and Gilead Sciences and expands the companies' U.S. joint
venture established in December 2004. The companies will work together
to complete regulatory filings in Canada and will share responsibility
for commercializing ATRIPLA in Canada, subject to regulatory approval
of the product. As in the United States, both companies will provide
funding and field-based sales representatives in support of
promotional efforts for ATRIPLA. Gilead will record revenues from
future net sales of ATRIPLA, while Bristol-Myers Squibb will record
revenues at percentages relative to the contribution represented by
its individual product.
"We are pleased to have finalized our agreement for Canada, and
are working expeditiously to complete the regulatory filing for
ATRIPLA with Health Canada," said John C. Martin, PhD, President and
CEO, Gilead Sciences. "We recognize the need for access to ATRIPLA,
the first once-daily single tablet regimen, and are working to make it
available to all patients who need it as quickly as possible."
"This agreement with Gilead Sciences marks an important step
forward in our efforts to deliver effective HIV therapies," said
Lamberto Andreotti, president, Worldwide Pharmaceuticals,
Bristol-Myers Squibb. "We look forward to working with Gilead Sciences
and Health Canada to make available another effective treatment option
for Canadian adult patients living with HIV/AIDS."
ATRIPLA combines SUSTIVA(R) (efavirenz), manufactured by
Bristol-Myers Squibb, and Truvada(R) (emtricitabine and tenofovir
disoproxil fumarate), manufactured by Gilead Sciences. Truvada itself
is a fixed-dose product that contains two of Gilead's anti-HIV
medications, Viread(R) (tenofovir disoproxil fumarate) and Emtriva(R)
(emtricitabine), in a single once-daily tablet for use as part of
combination therapy.
Important Safety Information About ATRIPLA, Truvada, Viread and
Emtriva
Lactic acidosis and severe hepatomegaly with steatosis, including
fatal cases, have been reported with the use of nucleoside analogues
alone or in combination with other antiretrovirals. ATRIPLA, Truvada,
Viread and Emtriva are not indicated for the treatment of chronic
hepatitis B virus (HBV) infection and the safety and efficacy of these
drugs have not been established in patients co-infected with HBV and
HIV. Severe acute exacerbations of hepatitis B have been reported in
patients who have discontinued Emtriva or Viread (components of
ATRIPLA and Truvada). Hepatic function should be monitored closely
with both clinical and laboratory follow-up for at least several
months in patients who discontinue ATRIPLA, Truvada, Emtriva or Viread
and are co-infected with HIV and HBV. If appropriate, initiation of
anti-hepatitis B therapy may be warranted.
Additional Important Information About ATRIPLA
In the United States, ATRIPLA is indicated for use alone as a
complete regimen or in combination with other antiretroviral agents
for the treatment of HIV-1 infection in adults.
It is important for patients to be aware that ATRIPLA does not
cure HIV infection or AIDS. ATRIPLA has not been shown to reduce the
risk of transmission of HIV to others through sexual contact or blood
contamination.
ATRIPLA is contraindicated for use with astemizole, cisapride,
midazolam, triazolam, ergot derivatives, or voriconazole. Concomitant
use of ATRIPLA and St. John's wort (Hypericum perforatum) or St.
John's wort-containing products is not recommended. Since ATRIPLA
contains efavirenz, emtricitabine and tenofovir disoproxil fumarate,
it should not be coadministered with SUSTIVA, Emtriva, Viread, or
Truvada. Due to similarities between emtricitabine and lamivudine,
ATRIPLA should not be coadministered with drugs containing lamivudine,
including Combivir(R), Epivir(R), Epivir-HBV(R), Epzicom(TM), or
Trizivir(R).
Serious psychiatric adverse experiences, including severe
depression (2.4%), suicidal ideation (0.7%), nonfatal suicide attempts
(0.5%), aggressive behavior (0.4%), paranoid reactions (0.4%) and
manic reactions (0.2%) have been reported in patients treated with
efavirenz. In addition to efavirenz, factors identified in a clinical
study that were associated with an increase in psychiatric symptoms
included a history of injection drug use, psychiatric history and use
of psychiatric medication. There have been occasional postmarketing
reports of suicide, delusions, and psychosis-like behavior, but it
could not be determined if efavirenz was the cause. Patients with
serious psychiatric adverse experiences should be evaluated
immediately to determine whether the risks of continued therapy
outweigh the benefits. Fifty-three percent of patients reported
central nervous system symptoms including dizziness (28.1%), insomnia
(16.3%), impaired concentration (8.3%), somnolence (7.0%), abnormal
dreams (6.2%) and hallucinations (1.2%) when taking efavirenz compared
to 25% of patients receiving control regimens. These symptoms usually
begin during the first or second day of therapy and generally resolve
after the first two to four weeks of therapy. After four weeks of
therapy, the prevalence of central nervous system symptoms of at least
moderate severity ranged from 5% to 9% in patients treated with
regimens containing efavirenz. Nervous system symptoms are not
predictive of the less frequent psychiatric symptoms.
ATRIPLA should not be given to patients with creatinine clearance
below 50 mL/min. Renal impairment, including cases of acute renal
failure and Fanconi syndrome (renal tubular injury with severe
hypophosphatemia), has been reported in association with the use of
tenofovir disoproxil fumarate, most often in patients with underlying
systemic or renal disease, or in patients taking concomitant
nephrotoxic agents. Some cases have occurred in patients with no
identified risk factors. ATRIPLA should be avoided with concurrent or
recent use of a nephrotoxic agent.
ATRIPLA may cause fetal harm when administered during the first
trimester to a pregnant woman. Women should not become pregnant or
breastfeed while taking ATRIPLA. Barrier contraception must always be
used in combination with other methods of contraception such as oral
or other hormonal contraceptives. If the patient becomes pregnant
while taking ATRIPLA, she should be apprised of the potential harm to
the fetus.
Mild to moderate rash is a common side effect of efavirenz. In
controlled clinical trials, 26% of patients treated with efavirenz
experienced new-onset skin rash compared with 17% of patients treated
in control groups. Skin discoloration, associated with emtricitabine,
may also occur. ATRIPLA should be discontinued in patients developing
severe rash associated with blistering, desquamation, mucosal
involvement, or fever. Liver enzymes should be monitored in patients
with known or suspected hepatitis B or C and when ATRIPLA is
administered with ritonavir or other medications associated with liver
toxicity. Decreases in bone mineral density have been seen with
tenofovir disoproxil fumarate. Use ATRIPLA with caution in patients
with a history of seizures. Convulsions have been observed in patients
receiving efavirenz, generally in the presence of known medical
history of seizures. Redistribution and/or accumulation of body fat
have been observed in patients receiving antiretroviral therapy.
Immune reconstitution syndrome has been reported in patients treated
with combination antiretroviral therapy, including the components of
ATRIPLA.
Coadministration of ATRIPLA and atazanavir is not recommended due
to concerns regarding decreased atazanavir concentrations. Patients on
lopinavir/ritonavir plus ATRIPLA should be monitored for
tenofovir-associated adverse events. ATRIPLA should be discontinued in
patients who develop tenofovir-associated adverse events.
Coadministration of ATRIPLA and didanosine should be undertaken with
caution. Patients receiving this combination should be monitored
closely for didanosine-associated adverse events. See full prescribing
information for complete list of drug-drug interactions.
In a large controlled clinical trial (Study 934), adverse events
observed in greater than or equal to 5% of patients in the
Viread/Emtriva/SUSTIVA group include dizziness, nausea, diarrhea,
fatigue, headache, and rash.
The dose of ATRIPLA is one tablet once daily taken orally on an
empty stomach. Dosing at bedtime may improve the tolerability of
nervous system symptoms.
Important Information About SUSTIVA
SUSTIVA (efavirenz) in combination with other antiretroviral
agents is indicated for the treatment of HIV-1 infection. This
indication is based on two clinical trials of at least one year
duration that demonstrated prolonged suppression of HIV RNA.
Coadministration with astemizole, cisapride, midazolam, triazolam,
ergot derivatives, or voriconazole is contraindicated. Concomitant use
of SUSTIVA and St. John's wort (Hypericum perforatum) or St. John's
wort-containing products is not recommended. This list of medications
is not complete.
Serious psychiatric adverse experiences, including severe
depression (2.4%), suicidal ideation (0.7%), nonfatal suicide attempts
(0.5%), aggressive behavior (0.4%), paranoid reactions (0.4%) and
manic reactions (0.2%) have been reported in patients treated with
SUSTIVA. In addition to SUSTIVA, factors identified in a clinical
study that were associated with an increase in psychiatric symptoms
included history of injection drug use, psychiatric history, and use
of psychiatric medication. There have been occasional reports of
suicide, delusions, and psychosis-like behavior, but it could not be
determined if SUSTIVA was the cause. Patients with serious psychiatric
adverse experiences should be evaluated immediately to determine
whether the risks of continued therapy outweigh the benefits.
Fifty-three percent of patients reported central nervous system
symptoms including dizziness (28.1%), insomnia (16.3%), impaired
concentration (8.3%), somnolence (7.0%), abnormal dreams (6.2%) and
hallucinations (1.2%) when taking SUSTIVA compared to 25% of patients
receiving control regimens. These symptoms usually begin during Days
1-2 of therapy and generally resolve after the first 2-4 weeks of
therapy. After four weeks of therapy, the prevalence of central
nervous system symptoms of at least moderate severity ranged from 5%
to 9% in patients treated with regimens containing SUSTIVA. Nervous
system symptoms are not predictive of the less frequent serious
psychiatric symptoms.
SUSTIVA may cause fetal harm when administered during the first
trimester to a pregnant woman. Women should not become pregnant or
breastfeed while taking SUSTIVA. Barrier contraception must always be
used in combination with other methods of contraception (e.g. oral or
other hormonal contraceptives). If the patient becomes pregnant while
taking SUSTIVA, she should be apprised of the potential harm to the
fetus.
Mild to moderate rash is a common side effect of SUSTIVA. In
controlled clinical trials, 26% of patients treated with SUSTIVA
experienced new-onset skin rash compared with 17% of patients treated
in control groups. SUSTIVA should be discontinued in patients
developing severe rash associated with blistering, desquamation,
mucosal involvement, or fever. Rash is more common and often more
severe in pediatric patients.
Liver enzymes should be monitored in patients with known or
suspected hepatitis B or C, in patients treated with other medications
associated with liver toxicity, and when SUSTIVA is administered with
ritonavir. Use SUSTIVA with caution in patients with a history of
seizures. Convulsions have been observed in patients receiving
efavirenz, generally in the presence of known medical history of
seizures. Redistribution and/or accumulation of body fat have been
seen in patients receiving antiretroviral therapy. A causal
relationship has not been established. Immune reconstitution syndrome
has been reported in patients treated with combination antiretroviral
therapy, including SUSTIVA.
It is recommended that SUSTIVA be taken on an empty stomach,
preferably at bedtime. The increased concentrations following
administration of SUSTIVA with food may lead to an increase in
frequency of adverse events. Dosing at bedtime may improve the
tolerability of nervous system symptoms.
Additional Important Information About Truvada
Truvada is a fixed-dose combination product that combines 200 mg
of Emtriva(R) (emtricitabine) and 300 mg of Viread(R) (tenofovir
disoproxil fumarate) in one tablet, taken once a day. In the United
States, Truvada is indicated in combination with other antiretroviral
agents (such as non-nucleoside reverse transcriptase inhibitors or
protease inhibitors) for the treatment of HIV-1 infection in adults.
Truvada should not be coadministered with Emtriva, Viread or
lamivudine-containing products and it is not recommended that Truvada
be used as a component of a triple nucleoside regimen. In
treatment-experienced patients, the use of Truvada should be guided by
laboratory testing and treatment history.
Clinical Study 934 supports the use of Truvada tablets for the
treatment of HIV-1 infection. Additional data in support of the use of
Truvada are derived from Study 903, in which Viread and lamivudine
were used in combination in treatment-naive adults, and clinical Study
303, in which Emtriva and lamivudine demonstrated comparable efficacy,
safety and resistance patterns as part of multidrug regimens.
No drug interaction studies have been conducted using Truvada.
Drug interactions have been observed when didanosine, atazanavir, or
lopinavir/ritonavir are co-administered with Viread, a component of
Truvada, and dose adjustments may be necessary. Data are not available
to recommend a dose adjustment of didanosine for patients weighing
less than 60 kg. Patients on atazanavir or lopinavir/ritonavir plus
Truvada should be monitored for Truvada-associated adverse events that
may require discontinuation. When co-administered with Truvada, it is
recommended that atazanavir 300 mg be given with ritonavir 100 mg.
Atazanavir without ritonavir should not be co-administered with
Truvada.
Four-hundred and forty-seven HIV-1 infected patients have received
combination therapy with Emtriva and Viread with either a
non-nucleoside reverse transcriptase inhibitor (Study 934) or protease
inhibitor for 48 weeks in clinical studies. Adverse events observed in
Study 934 were generally consistent with those seen in other studies
in treatment-experienced or treatment-naive patients receiving Viread
and/or Emtriva. Adverse events observed in more than 5% of patients in
the Viread/Emtriva group in Study 934 include diarrhea, nausea,
fatigue, headache, dizziness and rash.
Renal impairment, including cases of acute renal failure and
Fanconi syndrome (renal tubular injury with severe hypophosphatemia),
has been reported among patients taking Viread, a component of Truvada
(emtricitabine and tenofovir disoproxil fumarate). Renal impairment
occurred most often in patients with underlying systemic or renal
disease or in patients taking concomitant nephrotoxic agents, though
some cases have appeared in patients without identified risk factors.
Decreases in bone mineral density (BMD) at the lumbar spine and hip
have been seen with the use of Viread. Redistribution and/or
accumulation of body fat have been observed in patients receiving
antiretroviral therapy. Immune reconstitution syndrome has been
reported in patients treated with combination antiretroviral therapy
including Truvada, Viread and Emtriva.
The effects of Viread-associated changes in BMD and biochemical
markers on long-term bone health and future fracture risk are unknown.
Skin discoloration, manifested by hyperpigmentation on the palms
and/or soles, has been reported with the use of Emtriva, a component
of Truvada. Skin discoloration was generally mild and asymptomatic and
its mechanism and clinical significance are unknown.
The parent compound of Viread was discovered through a
collaborative research effort between Dr. Antonin Holy, Institute for
Organic Chemistry and Biochemistry, Academy of Sciences of the Czech
Republic (IOCB) in Prague and Dr. Erik DeClercq, Rega Institute for
Medical Research, Katholic University in Leuven, Belgium.
About Bristol-Myers Squibb
Bristol-Myers Squibb is a global pharmaceutical and related
healthcare products company. Visit Bristol-Myers Squibb on the World
Wide Web at www.bms.com.
About Gilead Sciences
Gilead Sciences is a biopharmaceutical company that discovers,
develops and commercializes innovative therapeutics in areas of unmet
medical need. The company's mission is to advance the care of patients
suffering from life-threatening diseases worldwide. Headquartered in
Foster City, California, Gilead has operations in North America,
Europe and Australia. Visit Gilead on the World Wide Web at
www.gilead.com.
Forward-Looking Statements
Bristol-Myers Squibb Forward-Looking Statement
This press release contains "forward-looking statements" as that
term is defined in the Private Securities Litigation Reform Act of
1995 regarding product development. Such forward-looking statements
are based on current expectations and involve inherent risks and
uncertainties, including factors that could delay, divert or change
any of them, and could cause actual outcomes and results to differ
materially from current expectations. No forward-looking statement can
be guaranteed. Among other risks, there can be no guarantee that the
combination product will receive regulatory approval in Canada or
other geographies, or, if approved, will be commercially successful.
Forward-looking statements in this press release should be evaluated
together with the many uncertainties that affect Bristol-Myers
Squibb's business, particularly those identified in the cautionary
factors discussion in Bristol-Myers Squibb's Annual Report on Form
10-K for the year ended December 31, 2005 and in our Quarterly Reports
on Form 10-Q. Bristol-Myers Squibb undertakes no obligation to
publicly update any forward-looking statement, whether as a result of
new information, future events or otherwise.
Gilead Forward-Looking Statement
This press release includes forward-looking statements, within the
meaning of the Private Securities Litigation Reform Act of 1995, that
are subject to risks, uncertainties and other factors, including that
the combination product receive regulatory approval in Canada or other
geographies, or, if approved, that physicians may not see advantages
of ATRIPLA over other antiretrovirals and may therefore be reluctant
to prescribe the product. These risks, uncertainties and other factors
could cause actual results to differ materially from those referred to
in the forward-looking statements. The reader is cautioned not to rely
on these forward-looking statements. These and other risks are
described in detail in the Gilead Annual Report on Form 10-K for the
year ended December 31, 2005, filed with the U.S. Securities and
Exchange Commission. All forward-looking statements are based on
information currently available to Gilead and Gilead assumes no
obligation to update any such forward-looking statements.
U.S. full prescribing information for ATRIPLA is available at
www.atripla.com.
U.S. full prescribing information for SUSTIVA is available at
www.bms.com.
U.S. full prescribing information for Truvada, Viread and Emtriva
is available at www.gilead.com.
ATRIPLA is a trademark of Bristol-Myers Squibb & Gilead Sciences,
LLC.
SUSTIVA is a registered trademark of Bristol-Myers Squibb Pharma
Company.
Truvada, Viread and Emtriva are registered trademarks of Gilead
Sciences, Inc.
