Bristol-Myers Squibb Company (NYSE:BMY) and Gilead Sciences, Inc.
(Nasdaq:GILD) announced today that Health Canada has approved
ATRIPLA(R) (efavirenz 600 mg/emtricitabine 200 mg/tenofovir disoproxil
fumarate 300 mg) for the treatment of HIV-1 infection in adults. With
this Notice of Compliance, ATRIPLA becomes the first once-daily single
tablet regimen for HIV approved in Canada for use as a stand-alone
therapy or in combination with other antiretrovirals.
ATRIPLA combines SUSTIVA(R) (efavirenz), manufactured by
Bristol-Myers Squibb Company, and Truvada(R) (emtricitabine/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. All three medicines work by blocking reverse
transcriptase, an enzyme necessary for HIV replication.
"ATRIPLA represents a milestone in treatment for this disease,"
said Mark Wainberg, MD, Director of the McGill AIDS Centre and
Professor of Medicine and Microbiology at McGill University. "I
commend the companies involved for joining forces to make ATRIPLA, the
first complete three-drug regimen in a single once-daily pill."
ATRIPLA was developed through a joint venture partnership between
Bristol-Myers Squibb Company and Gilead Sciences. The product was
approved by the U.S. Food and Drug Administration in July 2006 and has
since become the most-prescribed treatment regimen for patients
starting HIV therapy in the United States. In Canada, approximately
60,000 people are living with HIV, and around 2,500 new HIV diagnoses
are reported each year.
Clinical data support the use of the three-drug regimen contained
in ATRIPLA in HIV treatment-naive patients. A randomized, open label,
active-controlled, multicenter, non-inferiority study, Study 934,
compared a once-daily regimen of Viread, Emtriva and SUSTIVA, the
components of ATRIPLA, with twice-daily Combivir(R)
(lamivudine/zidovudine) and once-daily SUSTIVA in treatment-naive
patients with HIV. Through 48 weeks, 84 percent of patients in the
Viread/Emtriva/SUSTIVA group (n=244) compared to 73 percent of
patients in the Combivir/SUSTIVA group (n=243) achieved and maintained
a viral load of less than 400 copies/mL. This difference largely
results from the higher number of discontinuations in the
Combivir/SUSTIVA group due to adverse events (9 percent vs. 4 percent
in the Viread/Emtriva/SUSTIVA group) and other reasons including loss
to follow-up, patient withdrawal, non-compliance and protocol
violation (14 percent vs. 10 percent in the Viread/Emtriva/SUSTIVA
group).
In addition, 80 percent and 70 percent of patients in the
Viread/Emtriva/SUSTIVA group and the Combivir/SUSTIVA group,
respectively, achieved and maintained a viral load less than 50
copies/mL through 48 weeks. Selected treatment-emergent adverse events
(Grades 2-4) reported in greater than or equal to 5 percent of
patients in the Viread/Emtriva/SUSTIVA group through 48 weeks included
dizziness, nausea, diarrhea, fatigue, headache and rash.
Important Product Safety Information About ATRIPLA (efavirenz 600
mg/emtricitabine 200 mg/tenofovir disoproxil fumarate 300 mg), Emtriva
(emtricitabine), Viread (tenofovir disoproxil fumarate (DF)) and
Truvada (emtricitabine/tenofovir DF)
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.
Emtriva, Viread, Truvada and ATRIPLA are not approved for the
treatment of chronic hepatitis B virus (HBV) infection and their
safety and efficacy 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 Viread or Emtriva, which
are components of Truvada and ATRIPLA. In some of these patients
treated with Emtriva, the exacerbations of hepatitis B were associated
with liver decompensation and liver failure. Hepatic function should
be monitored closely with both clinical and laboratory follow-up for
at least several months in patients who are co-infected with HIV and
HBV and discontinue Truvada or ATRIPLA. If appropriate, initiation of
anti-hepatitis B treatment may be warranted.
It is important for patients to be aware that anti-HIV medicines
including Truvada, Viread, Emtriva, SUSTIVA and ATRIPLA do not cure
HIV infection or AIDS and do not reduce the risk of transmitting HIV
to others.
Additional Important Information About ATRIPLA
ATRIPLA(R) (efavirenz 600 mg/emtricitabine 200 mg/tenofovir
disoproxil fumarate (DF) 300 mg) 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.
Coadministration of ATRIPLA with astemizole, bepridil, cisapride,
midazolam, pimozide, triazolam, ergot derivatives, or voriconazole is
contraindicated. Concomitant use of ATRIPLA with St. John's wort
(Hypericum perforatum) or St. John's wort-containing products is not
recommended.
Since ATRIPLA contains efavirenz, emtricitabine, and tenofovir DF,
ATRIPLA should not be coadministered with SUSTIVA(R) (efavirenz),
Emtriva, Viread, or Truvada(R) (emtricitabine/tenofovir DF). Due to
similarities between emtricitabine and lamivudine, ATRIPLA should not
be coadministered with drugs containing lamivudine, including
Combivir(R) (lamivudine/zidovudine), Epivir(R) or Epivir-HBV(R)
(lamivudine), Epzicom(TM) (abacavir sulfate/lamivudine), or
Trizivir(R) (abacavir sulfate/lamivudine/zidovudine).
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 receiving
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 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 Days 1-2 of therapy and generally resolve after the first 2-4
weeks of therapy; they were severe in 2.0% of patients, and 2.1% of
patients discontinued therapy. After 4 weeks of therapy, the
prevalence of 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.
It is recommended that creatinine clearance (CrCl) be calculated
in all patients prior to initiating therapy and as clinically
appropriate during therapy with ATRIPLA, and routine monitoring of
CrCl and serum phosphorous be performed for patients at risk of renal
impairment. ATRIPLA should not be given to patients with CrCl less
than 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 DF. 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
breast-feed while taking ATRIPLA. Barrier contraception must always be
used in combination with other methods of contraception (eg, 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. ATRIPLA should be discontinued in patients
developing severe rash associated with blistering, desquamation,
mucosal involvement, or fever. Skin discoloration, associated with
emtricitabine, may also occur.
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 (BMD) have been seen with
tenofovir DF. Cases of osteomalacia (associated with proximal renal
tubulopathy) have been reported in association with the use of
tenofovir DF.
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/accumulation of body fat has 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.
Saquinavir should not be used as the only protease inhibitor in
combination with ATRIPLA.
Coadministration of ATRIPLA and atazanavir is not recommended due
to concerns regarding decreased atazanavir concentrations. Atazanavir
and lopinavir/ritonavir have been shown to increase tenofovir
concentrations. Patients on atazanavir or 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 with 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 Study 934, the most frequently reported grades 2-4 adverse
events through 48 weeks in patients receiving efavirenz +
emtricitabine + tenofovir DF were dizziness (8%), nausea (8%),
diarrhea (7%), fatigue (7%), headache (5%), rash (5%), sinusitis (4%),
depression (4%), insomnia (4%), and abnormal dreams (4%).
The dose of ATRIPLA is one tablet (containing 600 mg of efavirenz,
200 mg of emtricitabine, and 300 mg of tenofovir DF) once daily taken
orally on an empty stomach. Dosing at bedtime may improve the
tolerability of nervous system symptoms. ATRIPLA is not recommended
for use in patients less than 18 years of age.
For complete prescribing information for ATRIPLA, visit
www.atripla.com. For complete prescribing information for Sustiva,
visit www.bms.com. For complete prescribing information for Truvada,
Viread and Emtriva, visit www.gilead.com.
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 Canadian offices in Mississauga,
Ontario and manufacturing facilities in Edmonton, Alberta. The company
also has operations in 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
ATRIPLA will be made available on public formularies and private drug
plans as a reimbursed medication. Forward-looking statements in this
press release should be evaluated together with the many risks and
uncertainties that affect Bristol-Myers Squibb's business, including
those identified in Bristol-Myers Squibb's Annual Report on Form 10-K
for the year ended December 31, 2006 and in our Quarterly Reports on
Form 10-Q, particularly under "Item 1A. Risk Factors", 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 the
risk that physicians in Canada may not see advantages of ATRIPLA over
other antiretrovirals and may therefore be reluctant to prescribe the
product. In addition, Bristol-Myers Squibb Company and Gilead may be
unsuccessful in listing ATRIPLA on federal and provincial formularies
as a reimbursed medication. 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's Annual Report on Form 10-K for
the year ended December 31, 2006 and its Quarterly Report on Form 10-Q
for the first and second quarters of 2007, as 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 registered 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.
