BMY News Bristol-Myers Squibb and Gilead Sciences Establish Agreement to Commercialize ATRIPLA(TM) (efavirenz 600 mg/ emtricitabine 200 mg/ tenofovir disoproxil fumarate 300 mg) in Canada
PRINCETON, N.J. & FOSTER CITY, Calif.--(BUSINESS WIRE)--Bristol-Myers Squibb Company (NYSE:BMY) and Gilead Sciences, Inc.
(Nasdaq:GILD) today announced an agreement to commercialize ATRIPLATM
(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®
(efavirenz), manufactured by Bristol-Myers Squibb, and Truvada®
(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®
(tenofovir disoproxil fumarate) and Emtriva®
(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®,
Epivir®, Epivir-HBV®,
EpzicomTM, or Trizivir®.
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®
(emtricitabine) and 300 mg of Viread®
(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-naïve 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-naïve
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.
