European CHMP Issues Positive Opinion For ATRIPLA(R) (Efavirenz 600mg/Emtricitabine 200 Mg/Tenofovir Disoproxil Fumarate 300 Mg)
Bristol-Myers Squibb Company (NYSE:BMY), Gilead Sciences, Inc. (Nasdaq:GILD) and Merck &
Co., Inc. (NYSE:MRK) announced that the Committee after Medicinal Products championing Human Use
(CHMP) of the European Medicines Intervention (EMEA) has issued a unmitigated appreciation on the Marketing
Authorisation Application for ATRIPLA(R) (efavirenz 600mg/emtricitabine 200 mg/tenofovir
disoproxil fumarate 300 mg). Specifically, the CHMP has recommended ATRIPLA for the treatment
of human immunodeficiency virus-1 (HIV-1) infection in adults with virologic putting down to HIV-1
RNA levels of less than 50 copies/ml on their tenor amalgam antiretroviral therapy into more than
three months. Patients forced to not have experienced virological default on any prior antiretroviral therapy
and must be known not to have harbored virus strains with mutations conferring significant resistance
to any of the three components contained in ATRIPLA whilom before to initiation of their start antiretroviral
treatment regimen.
The CHMP’s positive recommendation will be reviewed by the European Commission, which has the
arbiter government to approve medicinal products proper for deplete in the 27 countries of the European Union. The
companies expect the European Commission to take exception its decision on the marketing authorization for
ATRIPLA toward the cease of the year. Once granted by the European Commission, ATRIPLA would
report the first and only once-daily apart tablet regimen an eye to many HIV/AIDS patients in the
European Confederating.
“Each of the components in ATRIPLA has been shown to be effective and has a well-established
tolerability avail in HIV patients,” said Brian Gazzard, MD, Clinical Inspection Director, Chelsea and
Westminster Hospital, London. “This first Possibly man-pill-a-hour treatment for HIV represents a simplification
of dosing, which is important as patients tarry on therapy longer.”
Efavirenz is marketed by Bristol-Myers Squibb inferior to the tradename SUSTIVA(R) in the Of like mind
States, Canada and six European countries (France, Germany, Republic of Ireland, Italy, Spain and the
United Kingdom). In other territories, including all other countries of the European Union, efavirenz is
commercialized by Merck & Co., Inc., (known as Merck Sharp & Dohme (MSD) in sundry countries
outside of the Harmonious States) and is marketed in most of these countries comprised in the tradename
Stocrin(R). Emtricitabine and tenofovir disoproxil fumarate are commercialized by Gilead under the
tradenames Emtriva(R) and Viread(R), severally, and are commonly prescribed together as a oncedaily, fixed-prescribe troche, marketed under the tradename Truvada(R) for throw away as partially of amalgamation
therapy.
The MAA for ATRIPLA in the European Joint was filed jointly by the three companies on account of a
three-way joint make bold based in Ireland called Bristol-Myers Squibb Gilead Sciences And Merck
Sharp & Dohme Limited.
ATRIPLA is currently the start with and simply once-daily single tablet regimen approved for the treatment of
HIV-1 infection in adults in the United States proper for squander either as stand-simply therapy or in combination
with other antiretroviral agents. ATRIPLA was approved by the U.S. Food and Analgesic Administration
 
(FDA) in July 2006 and has since become the most-prescribed treatment regimen for patients starting
HIV treatment in the Harmonious States.
The FDA also granted approval of an alternate tradedress of ATRIPLA object of developing countries,
where ATRIPLA is being made nearby as a white-colored tablet to particularize it from the salmoncolored variation currently available in the United States. In August 2006, Gilead and Merck established
an agreement for classification of the artifact in developing countries, and in Strut 2007, the World
Health Consortium added ATRIPLA to its Model Listing of Essential Medicines.
Notable Issue Protection 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) in the United States
Lactic acidosis and severe hepatomegaly with steatosis, including final 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 long-lived hepatitis B
virus (HBV) infection and their safety and efficacy have not been established in patients co-infected
with HBV and HIV. Critical acute exacerbations of hepatitis B have in the offing been reported in patients who from
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 also-ran. Hepatic task 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 assign, investiture of anti-hepatitis B treatment may be
warranted.
It is important suitable 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 On every side ATRIPLA in the United States
ATRIPLA(R) (efavirenz 600 mg/emtricitabine 200 mg/tenofovir disoproxil fumarate 300 mg) is
indicated seeking use solely 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 savage the blues (2.4%), suicidal ideation (0.7%),
nonfatal suicide attempts (0.5%), litigious behavior (0.4%), paranoid reactions (0.4%), and manic
reactions (0.2%), have been reported in patients receiving efavirenz. In furthermore to efavirenz, factors
identified in a clinical study that were associated with an wax in psychiatric symptoms included a
 
history of injection sedative use, psychiatric depiction, and use of psychiatric medication. There have been
periodic reports of suicide, delusions, and psychosis-approve of behavior, but it could not be stubborn if
efavirenz was the lead to. Patients with serious psychiatric adverse experiences should be evaluated
directly to detect whether the risks of continued therapy outweigh the benefits.
Fifty-three percent of patients reported central disturbed system symptoms (including dizziness
(28.1%), insomnia (16.3%), impaired concentration (8.3%), somnolence (7.0%), unnatural dreams
(6.2%), and hallucinations (1.2%)) when taking efavirenz compared to 25% of patients receiving
control regimens. These symptoms inveterately off during Days 1-2 of analysis and in a general way settle
after the first 2-4 weeks of remedy; they were autocratic in 2.0% of patients, and 2.1% of patients
discontinued therapy. After 4 weeks of therapy, the ubiquity of nervous practice 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 numerous psychiatric symptoms.
It is recommended that creatinine clearance (CrCl) be calculated in all patients prior to initiating
therapy and as clinically seemly during therapy with ATRIPLA, and programmed monitoring of CrCl
and serum phosphorous be performed for patients at imperil of renal weakening. ATRIPLA should not be
given to patients with CrCl less than 50 mL/min. Renal enfeeblement, including cases of astute renal
loser and Fanconi syndrome (renal tubular injury with severe hypophosphatemia), has been reported
in combine with the use of tenofovir DF. ATRIPLA should be avoided with concurrent or late
serviceability of a nephrotoxic deputy.
ATRIPLA may genesis fetal wound when administered during the first trimester to a heavy with child dame.
Women should not become expecting or breast-feed while bewitching ATRIPLA. Barrier contraception
forced to always be used in amalgam with other methods of contraception (eg, oral or other hormonal
contraceptives). If the indefatigable becomes enceinte while fetching ATRIPLA, she should be apprised of the
potential harm to the fetus.
Mild-to-moderate rash is a mutual side begin of efavirenz. In controlled clinical trials, 26% of
patients treated with efavirenz experienced new-onset skin audacious 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. Hide discoloration, associated with
emtricitabine, may also come to pass.
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 good of
tenofovir DF.
Use ATRIPLA with tip off in patients with a biography of seizures. Convulsions play a joke on been observed in
patients receiving efavirenz, loosely in the adjacency of known medical history of seizures.
Redistribution/accumulation of trunk riches has been observed in patients receiving antiretroviral therapy.
Immune reconstitution syndrome has been reported in patients treated with compound antiretroviral
therapy, including the components of ATRIPLA.
Saquinavir should not be employed 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 press been shown to growing
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 U.S. Loud
Prescribing Information for whole list of drug-drug interactions.
In Look at 934, the most over 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%), devil-may-care (5%), sinusitis (4%), depression (4%), insomnia (4%), and
extraordinary dreams (4%).
The administer of ATRIPLA is the same slab (containing 600 mg of efavirenz, 200 mg of emtricitabine, and
300 mg of tenofovir DF) in one go daily enchanted orally on an empty suffer. Dosing at bedtime may
improve the tolerability of perturbed system symptoms. ATRIPLA is not recommended for use in
patients less than 18 years of age.
In spite of complete U.S. prescribing low-down for ATRIPLA, visit www.atripla.com. For complete
prescribing low-down in the interest of Sustiva, inflict www.bms.com. Quest of complete U.S. prescribing information
for Truvada, Viread and Emtriva, visit http://www.gilead.com.
Here Bristol-Myers Squibb
Bristol-Myers Squibb is a global pharmaceutical and joint healthcare products company. Befall
Bristol-Myers Squibb on the World Wide Snare at http://www.bms.com.
About Gilead Sciences
Gilead Sciences is a biopharmaceutical partnership that discovers, develops and commercializes
innovative therapeutics in areas of unmet medical requirement. The company’s mission is to advance the charge
of patients suffering from effervescence-menacing diseases worldwide. Headquartered in Back City,
California, Gilead has operations in North America, Europe and Australia. Visit Gilead on the Society
Wide Web at http://www.gilead.com.
Prevalent Merck
Merck & Co. Inc., which operates in many countries as Merck Sheer & Dohme (MSD), 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 spread access to medicines through
far-reaching programs that not only donate Merck medicines but also help set free them to the people
who need them. Merck also publishes unbiased form information as a not-for-profit maintenance. For more
information, visit http://www.merck.com.
Forward-Looking Statements
Bristol-Myers Squibb Forwards-Looking Statement
This press release contains “forward-looking statements” as that term is defined in the Private
Securities Litigation Reform Order of 1995 re by-product circumstance. Such forward-looking
statements are based on current expectations and involve inherent risks and uncertainties, including
factors that could delay, divert or difference any of them, and could cause present outcomes and results to
differ much from current expectations. No forward-looking expression can be guaranteed. Expanse
other risks, there can be no make sure that the federation product will receive regulatory approval in
the European Mixture or other geographies. Forward-looking statements in this meet 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 Check out on Form 10-K in the interest of the year ended
December 31, 2006 and in our Quarterly Reports on Form 10-Q, only under “Item 1A. Risk
Factors”. Bristol-Myers Squibb undertakes no covenant to publicly update any forward-looking
statement, whether as a result of new information, tomorrow’s events or under other circumstances.
Gilead Forward-Looking Statement
This press publicity includes first-looking statements, within the meaning of the Private Securities
Litigation Reform Edict of 1995, that are subject to risks, uncertainties and other factors, including the
imperil that the European Commission will not formally approve ATRIPLA for marketing in the
European Union prior to the end of the year or at all, and any marketing approval, if granted, may have
significant limitations on its use. In addition, Gilead, Bristol-Myers Squibb and Merck may be unable
to reach concord related to the manufacture, commercialization and distribution of ATRIPLA in the
European Union in a convenient manner or at all. These risks, uncertainties and other factors could cause
physical results to be dissimilar materially from those referred to in the promote-looking statements. The reader
is cautioned not to rely on these forward-looking statements. These and other risks are described in
spell out in the Gilead’s Annual Scrutinize on Form 10-K for the year ended December 31, 2006 and its
Four times a year Reports on Form 10-Q for the first two quarters of 2007, 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 Audacious-Looking Statement
This press turn loose contains “forward-looking statements” as that term is defined in the Private
Securities Litigation Reform Turn of 1995. These statements are based on management’s current
expectations and involve risks and uncertainties, which may occasion results to take issue materially from
those set forth in the statements. The unabashed-looking statements may tabulate statements regarding
commodity progress, work potential or fiscal performance. No on to the table-looking announcement can
be guaranteed and actual results may differ materially from those projected. Merck undertakes no
promise to publicly update any forward-looking statement, whether as a result of new information,
prospective events, or otherwise. Forward-looking statements in this multitude release should be evaluated
together with the many uncertainties that attack Merck’s business, particularly those mentioned in the
risk factors and cautionary statements in Note 1A of Merck’s Form 10-K also in behalf of the year ended Dec. 31,
2006, and in its periodic reports on Form 10-Q and Formality 8-K, which the Company incorporates by
quotation.
Harsh U.S. prescribing information fitted ATRIPLA is available at http://www.atripla.com.
Full U.S. prescribing information for SUSTIVA is available at http://www.bms.com.
Wholly U.S. prescribing advice for Truvada, Viread and Emtriva are available at http://www.gilead.com.
EU Summary of Product Characteristics for Truvada, Viread, Emtriva, SUSTIVA and Stocrin are
at one’s disposal here.
ATRIPLA is a registered trademark of Bristol-Myers Squibb & Gilead Sciences, LLC.
SUSTIVA is a registered trademark of Bristol-Myers Squibb Pharma Company.
Stocrin is a registered trademark of Merck & Co., Inc.
Truvada, Viread and Emtriva are all registered trademarks of Gilead Sciences, Inc.
http://www.emea.europa.eu/
Considering deaden information on Combivir; Epivir; Sustiva.
Eric Gilbert