- Product Developed Through Joint Venture Between Bristol-Myers Squibb
Company and Gilead Sciences, the First of Its Kind in HIV Treatment -
PRINCETON, N.J. and FOSTER CITY, Calif., Oct. 17 /PRNewswire-FirstCall/
-- 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(R) (emtricitabine), Viread(R) (tenofovir disoproxil fumarate), 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 <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 (e.g., 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 <18 years
of age.
For complete prescribing information for ATRIPLA, visit
http://www.atripla.com. For complete prescribing information for Sustiva, visit
http://www.bms.com. For complete prescribing information for Truvada, Viread and
Emtriva, visit http://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
http://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
http://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
http://www.ATRIPLA.com.
U.S. full prescribing information for SUSTIVA is available at
http://www.bms.com. U.S. full prescribing information for Truvada, Viread and
Emtriva is available
at http://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.
SOURCE Bristol-Myers Squibb Company
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Related links:
http://www.bms.com
http://www.ATRIPLA.com http://www.gilead.com
CONTACT:
Media, Sonia Choi, +1-609-252-5132, Marc
Osborne, +1-514-333-2463, or Investors, John Elicker,
+1-212-546-3775, all of Bristol-Myers Squibb; or Media, Cara
Miller, +1-650-522-1616, or Investors, Susan Hubbard,
+1-650-522-5715, both of Gilead Sciences
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