Gilead Sciences and Merck Establish Agreement for Distribution of ATRIPLA(TM) in Developing Countries
FOSTER CITY, Calif. & WHITEHOUSE STATION, N.J.--(BUSINESS
WIRE)--Aug. 11, 2006--Gilead Sciences, Inc. (Nasdaq: GILD) and Merck &
Co., Inc. (NYSE: MRK) today announced that the companies have
established an agreement for the distribution of ATRIPLA(TM)
(efavirenz 600 mg/ emtricitabine 200 mg/ tenofovir disoproxil fumarate
300 mg), a once-daily, single tablet regimen for the treatment of
HIV-1 infection in adults, in developing countries around the world.
ATRIPLA contains 600 mg of efavirenz, a non-nucleoside reverse
transcriptase inhibitor (NNRTI), 200 mg of emtricitabine and 300 mg of
tenofovir disoproxil fumarate, both nucleoside reverse transcriptase
inhibitors (NRTIs). Efavirenz is marketed by Merck under the tradename
Stocrin(R) in all territories outside of the United States, Canada and
certain European countries (where it is commercialized by
Bristol-Myers Squibb under the tradename Sustiva(R)). Emtricitabine
and tenofovir disoproxil fumarate are commercialized by Gilead
Sciences under the tradenames Emtriva(R) and Viread(R), respectively.
The compounds are commonly prescribed together as a once-daily,
fixed-dose tablet, marketed under the tradename Truvada(R) for use as
part of combination therapy.
ATRIPLA was approved by the U.S. Food and Drug Administration
(FDA) on July 12, 2006. In the United States, the product is
commercialized by Bristol-Myers Squibb and Gilead Sciences through the
companies' joint venture. The FDA also granted approval of an
alternate tradedress of ATRIPLA for developing countries, where
ATRIPLA will be made available as a white-colored tablet to
distinguish it from the salmon-colored version currently available in
the United States. Gilead and Merck plan to pursue registration of the
product with individual country health authorities. The component
therapies are already registered, or in the process of being
registered, in many of these countries.
"The FDA's rapid review and approval of ATRIPLA will help to
expedite access for adults infected with HIV-1 living in
resource-limited parts of the world," said John C. Martin, PhD,
President and CEO, Gilead Sciences. "As a once-daily, single tablet
regimen, ATRIPLA may help to simplify therapy for patients, and we
recognize the urgent need to ensure access for people living in parts
of the world where the epidemic is taking the greatest toll."
"Merck has long been a leader in efforts to broaden access to
medicines and vaccines around the world," said Merck Chief Executive
Officer and President Richard T. Clark. "This new single-tablet
regimen is the latest example of how we are working to fulfill our
mission to put patients first. We look forward to collaborating with
Gilead and national health authorities to deliver ATRIPLA to those who
need it as soon as possible."
Under the terms of the agreement, Gilead will manufacture ATRIPLA
using efavirenz supplied by Merck. Merck in turn will handle
distribution of the product in the countries covered by the agreement.
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
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 efavirenz, Emtriva, Viread, or
Truvada. Due to similarities between emtricitabine and lamivudine,
ATRIPLA should not be coadministered with drugs containing lamivudine,
including Combivir, 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 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/efavirenz 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 Efavirenz
Efavirenz 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 efavirenz 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
efavirenz. In addition to efavirenz, 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 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. 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
serious psychiatric symptoms.
Efavirenz may cause fetal harm when administered during the first
trimester to a pregnant woman. Women should not become pregnant or
breastfeed while taking efavirenz. 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 efavirenz, 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. Efavirenz 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 efavirenz is administered
with ritonavir. Use efavirenz 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 efavirenz.
It is recommended that efavirenz be taken on an empty stomach,
preferably at bedtime. The increased concentrations following
administration of efavirenz 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 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.
About Merck
Merck & Co., Inc. is a global research-driven pharmaceutical
company dedicated to putting patients first. Established in 1891,
Merck currently discovers, develops, manufactures and markets vaccines
and medicines to address unmet medical needs. The Company devotes
extensive efforts to increase access to medicines through far-reaching
programs that not only donate Merck medicines but also help deliver
them to the people who need them. Merck also publishes unbiased health
information as a not-for-profit service. For more information, visit
www.merck.com.
Forward-Looking Statements
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 and regulatory agencies 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.
Merck Forward-Looking Statement
This press release contains "forward-looking statements" as that
term is defined in the Private Securities Litigation Reform Act of
1995. These statements are based on management's current expectations
and involve risks and uncertainties, which may cause results to differ
materially from those set forth in the statements. The forward-looking
statements may include statements regarding product development,
product potential or financial performance. No forward-looking
statement can be guaranteed, and actual results may differ materially
from those projected. Merck undertakes no obligation to publicly
update any forward-looking statement, whether as a result of new
information, future events, or otherwise. Forward-looking statements
in this press release should be evaluated together with the many
uncertainties that affect Merck's business, particularly those
mentioned in the cautionary statements in Item 1 of Merck's Form 10-K
for the year ended Dec. 31, 2005, and in its periodic reports on Form
10-Q and Form 8-K, which the Company incorporates by reference.
Full prescribing information for ATRIPLA is available at
www.atripla.com.
Full prescribing information for Stocrin is available at
http://www.emea.eu.int/humandocs/Humans/EPAR/Stocrin/Stocrin.htm
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.
Stocrin is a registered trademark of Merck & Co., Inc.
Truvada, Viread and Emtriva are registered trademarks
of Gilead Sciences, Inc.
Sustiva is a registered trademark of Bristol-Myers Squibb.
CONTACT: Gilead Sciences, Inc.
James Loduca, 650-522-5908 (Media)
Susan Hubbard, 650-522-5715 (Investors)
or
Merck & Co.
Chris Loder, 908-423-3786 (Corporate Media Relations)
Graeme Bell, 908-423-5185 (Investor Relations)
SOURCE: Gilead Sciences, Inc.
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