UPDATE: With Multimedia: U.S. FDA Approves ELIQUIS® (apixaban) to Reduce the Risk of Stroke and Systemic Embolism in Patients

  UPDATE: With Multimedia: U.S. FDA Approves ELIQUIS® (apixaban) to Reduce the
  Risk of Stroke and Systemic Embolism in Patients with Nonvalvular Atrial
  Fibrillation

  ELIQUIS Demonstrated Superior Risk Reductions Versus Warfarin in Three Key
     Outcomes—Stroke and Systemic Embolism, Major Bleeding and All-Cause
         Mortality—for Patients with Nonvalvular Atrial Fibrillation

Business Wire

PRINCETON, N.J. & NEW YORK -- January 2, 2013

Bristol-Myers Squibb Company (NYSE: BMY) and Pfizer Inc. (NYSE: PFE) announced
that the U.S. Food and Drug Administration (FDA) approved ELIQUIS^® (apixaban)
to reduce the risk of stroke and systemic embolism in patients with
nonvalvular atrial fibrillation. Atrial fibrillation, the most common type of
irregular heartbeat, affects approximately 5.8 million people in the U.S., and
results in a five times greater risk of stroke. In the U.S., 15 percent of
strokes are attributable to atrial fibrillation.

“The approval of ELIQUIS offers patients with nonvalvular atrial fibrillation
a novel treatment option for reducing the risk of stroke,” said Lamberto
Andreotti, chief executive officer, Bristol-Myers Squibb. “ELIQUIS is the
result of leading scientific innovation and the shared vision of our alliance
to introduce a new oral anticoagulant for patients with nonvalvular atrial
fibrillationin the U.S.”

Ian Read, chairman and chief executive officer, Pfizer Inc. said, “The profile
of ELIQUIS, combined with the strong legacy and complementary capabilities
that Pfizer and Bristol-Myers Squibb have in the cardiovascular space,
positions us well to deliver this important new treatment option to patients
and health care professionals.”

The ELIQUIS clinical trial program is the largest completed clinical
development program designed to evaluate risk reduction of stroke or systemic
embolism in nonvalvular atrial fibrillation patients; it included two landmark
Phase 3 studies -- ARISTOTLE and AVERROES -- in patients with nonvalvular
atrial fibrillation and at least one additional risk factor for stroke.
ARISTOTLE evaluated ELIQUIS versus warfarin in 18,201 patients with
nonvalvular atrial fibrillation who were suitable for warfarin therapy, and
AVERROES evaluated ELIQUIS versus aspirin in 5,598 patients with nonvalvular
atrial fibrillation who were considered unsuitable for treatment with
warfarin.

The Full Prescribing Information for ELIQUIS includes a Boxed Warning for
patients who discontinue treatment. Patients on ELIQUIS who discontinue
treatment are at an increased risk of thrombotic events. An increased rate of
stroke was observed following discontinuation of ELIQUIS in clinical trials in
patients with nonvalvular atrial fibrillation. If anticoagulation with ELIQUIS
must be discontinued for a reason other than pathological bleeding, coverage
with another anticoagulant should be strongly considered.

ELIQUIS increases the risk of bleeding and can cause serious, potentially
fatal bleeding. Please see additional Important Safety Information included in
this release.

“With a population that is living longer, the prevalence of nonvalvular atrial
fibrillation is increasing, but many patients are still not being managed
effectively with warfarin,” said Christopher Granger, M.D., Professor of
Medicine, Duke Clinical Research Institute, Duke University Medical Center,
Durham, N.C., ARISTOTLE lead investigator. “ELIQUIS represents a significant
advance over warfarin for health care professionals to reduce the risk of
stroke in patients with nonvalvular atrial fibrillation.”

ELIQUIS is an oral Factor Xa inhibitor anticoagulant. By inhibiting Factor Xa,
a key blood clotting protein, ELIQUIS decreases thrombin generation and blood
clot formation. ^ ELIQUIS does not require routine monitoring using
International Normalized Ratio (INR) or other tests of coagulation and there
are no known dietary restrictions. ELIQUIS can be taken with or without food.

ELIQUIS is expected to be widely available in the U.S. by the end of January
2013.

Efficacy and Safety Profile of ELIQUIS in Patients with Nonvalvular Atrial
Fibrillation

The ARISTOTLE (Apixaban for Reduction in Stroke and Other Thromboembolic
Events in Atrial Fibrillation) study was designed to compare the effects of
ELIQUIS and warfarin on the risk of stroke and systemic embolism. In
ARISTOTLE, 18,201 patients were randomized (9,120 patients to ELIQUIS and
9,081 to warfarin) and were followed for a median of 1.7 years. ARISTOTLE was
a double-blind, multi-national trial in patients with nonvalvular atrial
fibrillation, and one or more of the following additional risk factors for
stroke: prior stroke or transient ischemic attack, prior systemic embolism,
age ≥75 years, arterial hypertension requiring treatment, diabetes mellitus,
heart failure ≥New York Heart Association Class 2, or left ventricular
ejection fraction ≤40%. Patients received treatment with ELIQUIS 5 mg orally
twice daily (or 2.5 mg twice daily in patients with at least 2 of the
following characteristics: age ≥80 years, body weight ≤60 kg, or serum
creatinine ≥1.5 mg/dL) or warfarin (target INR range 2.0-3.0).

ELIQUIS is the only oral anticoagulant to demonstrate superior risk reductions
versus warfarin in three key outcomes—stroke and systemic embolism, major
bleeding, and all-cause mortality—for patients with nonvalvular atrial
fibrillation.

In ARISTOTLE, ELIQUIS was superior to warfarin in the primary efficacy
endpoint of stroke or systemic embolism, with a 21% relative risk reduction
beyond warfarin (1.27%/year versus 1.60%/year, HR=0.79, p=0.01). Superiority
to warfarin was primarily attributable to a reduction in hemorrhagic stroke
and ischemic stroke that converted to hemorrhagic stroke. Purely ischemic
strokes occurred with similar rates on both drugs.

ELIQUIS was superior to warfarin for the primary safety endpoint of major
bleeding, with a 31% relative risk reduction (2.13%/year versus 3.09%/year,
HR=0.69, p<0.0001). Major bleeding was defined as clinically overt bleeding
that was accompanied by one or more of the following: a decrease in hemoglobin
of 2 g/dL or more; a transfusion of 2 or more units of packed red blood cells;
bleeding that occurred in at least one of the following critical sites:
intracranial, intraspinal, intraocular, pericardial, intra-articular,
intramuscular with compartment syndrome, retroperitoneal; or bleeding that was
fatal.

The incidence of major gastrointestinal (GI) bleeds was lower with ELIQUIS
compared to warfarin (0.83%/year versus 0.93%/year, HR=0.89 [CI=0.70, 1.14]).
GI bleed includes upper GI, lower GI, and rectal bleeding. ELIQUIS
demonstrated a significant reduction in intracranial hemorrhage versus
warfarin with a 59% relative risk reduction (0.33%/year versus 0.82%/year,
HR=0.41 [CI=0.30, 0.57]). Intracranial hemorrhage included intracerebral
(hemorrhagic stroke), subarachnoid, and subdural bleeds. The incidence of
major intraocular bleeding was numerically higher with ELIQUIS compared to
warfarin (0.21%/year versus 0.14%/year, HR=1.42 [CI=0.83, 2.45]). Intraocular
bleed is within the corpus of the eye (a conjunctival bleed is not an
intraocular bleed). ELIQUIS demonstrated a significant reduction in fatal
bleeds versus warfarin with a 73% relative risk reduction (0.06%/year versus
0.24%/year, HR=0.27 [CI=0.13, 0.53]). Fatal bleed is an adjudicated death
because of bleeding during the treatment period and includes both fatal
extracranial bleeds and fatal hemorrhagic stroke. Eliquis demonstrated a
significant reduction in clinically relevant non major bleeding (CRNM) versus
warfarin (2.08%/year for ELIQUIS compared to 3.00%/year for warfarin [HR=
0.70, P<0.0001]). CRNM was defined as clinically overt bleeding that did not
satisfy the criteria for major bleeding and that led to hospital admission,
physician-guided medical or surgical treatment, or a change in antithrombotic
therapy.

In AVERROES, ELIQUIS was associated with an increase in major bleeding
compared to aspirin that was not statistically significant (1.41%/year versus
0.92%/year, HR1.54, (95%CI, 0.96 to 2.45); P=0.07).

ELIQUIS was superior to warfarin in the key secondary endpoint of all-cause
mortality, with an 11% relative risk reduction (3.5%/year versus 3.9%/year,
HR=0.89, p= 0.046), ^ primarily because of a reduction in cardiovascular
death, particularly stroke deaths. Non-vascular death rates were similar in
the treatment arms.

The most common and most serious adverse reactions observed in the ARISTOTLE
and AVERROES clinical trials with ELIQUIS were related to bleeding. The most
common reason for treatment discontinuation was for bleeding-related adverse
reactions; in ARISTOTLE, this occurred in 1.7% and 2.5% of patients treated
with ELIQUIS and warfarin, respectively. Patients taking ELIQUIS should be
carefully observed and counseled on the symptoms and signs of bleeding.

The FDA has determined that a Risk Evaluation and Mitigation Strategy (REMS)
is necessary to ensure that the benefits of ELIQUIS outweigh the potential
risks in patients with nonvalvular atrial fibrillation. The ELIQUIS REMS
consists of a communication plan to inform healthcare professionals about the
increased risk of thrombotic events, including stroke when discontinuing
ELIQUIS without an adequate alternative anticoagulant and the importance of
following the recommendations in the U.S. Prescribing Information on how to
convert patients with nonvalvular atrial fibrillation from ELIQUIS to warfarin
or other anticoagulants.

ELIQUIS Dosage and Administration

The recommended dose of ELIQUIS for most patients is 5 mg taken orally twice
daily. In patients with any two of the following characteristics (age ≥80
years, body weight ≤60 kg, or serum creatinine ≥1.5mg/dL), the recommended
dose of ELIQUIS is 2.5 mg twice daily. The dose of ELIQUIS should be decreased
to 2.5 mg twice daily when coadministered with drugs that are strong dual
inhibitors of CYP3A4 and P-gp, (e.g., ketoconazole, itraconazole, ritonavir,
or clarithromycin). In patients already taking 2.5 mg twice daily, avoid
coadministration of ELIQUIS with strong dual inhibitors of CYP3A4 and P-gp.
ELIQUIS should be discontinued at least 48 hours prior to elective surgery or
invasive procedures with a moderate or high risk of unacceptable or clinically
significant bleeding. ELIQUIS should be discontinued at least 24 hours prior
to elective surgery or invasive procedures with a low risk of bleeding or
where the bleeding would be non-critical in location and easily controlled.
For more detailed information on the dosing of ELIQUIS, please refer to
Section 2 of the Full Prescribing Information.

IMPORTANT SAFETY INFORMATION for ELIQUIS^® (apixaban) 2.5 mg and 5 mg tablets


WARNING: DISCONTINUING ELIQUIS IN PATIENTS WITHOUT ADEQUATE CONTINUOUS
ANTICOAGULATION INCREASES RISK OF STROKE.

Discontinuing ELIQUIS places patients at an increased risk of thrombotic
events. An increased rate of stroke was observed following discontinuation of
ELIQUIS in clinical trials in patients with nonvalvular atrial fibrillation.
If anticoagulation with ELIQUIS must be discontinued for a reason other than
pathological bleeding, coverage with another anticoagulant should be strongly
considered.

CONTRAINDICATIONS

  *Active pathological bleeding
  *Severe hypersensitivity reaction to ELIQUIS (apixaban) (i.e., anaphylactic
    reactions)

WARNINGS AND PRECAUTIONS

  *Increased Risk of Stroke with Discontinuation of ELIQUIS: Discontinuing
    ELIQUIS in the absence of adequate alternative anticoagulation increases
    the risk of thrombotic events. An increased rate of stroke was observed
    during the transition from ELIQUIS to warfarin in clinical trials in
    patients with nonvalvular atrial fibrillation. If ELIQUIS must be
    discontinued for a reason other than pathological bleeding, consider
    coverage with another anticoagulant.
  *Bleeding Risk: ELIQUIS increases the risk of bleeding and can cause
    serious, potentially fatal bleeding. Concomitant use of drugs affecting
    hemostasis increases the risk of bleeding including aspirin and other
    anti-platelet agents, other anticoagulants, heparin, thrombolytic agents,
    SSRIs, SNRIs, and NSAIDs. Patients should be made aware of signs or
    symptoms of blood loss and instructed to immediately report to an
    emergency room. Discontinue ELIQUIS in patients with active pathological
    hemorrhage.
  *There is no established way to reverse the anticoagulant effect of
    apixaban, which can be expected to persist for about 24 hours after the
    last dose (i.e., about two half-lives). A specific antidote for ELIQUIS is
    not available. Because of high plasma protein binding, apixaban is not
    expected to be dialyzable. Protamine sulfate and vitamin K would not be
    expected to affect the anticoagulant activity of apixaban. There is no
    experience with antifibrinolytic agents (tranexamic acid, aminocaproic
    acid) in individuals receiving apixaban. There is neither scientific
    rationale for reversal nor experience with systemic hemostatics
    (desmopressin and aprotinin) in individuals receiving apixaban. Use of
    procoagulant reversal agents such as prothrombin complex concentrate,
    activated prothrombin complex concentrate, or recombinant factor VIIa may
    be considered but has not been evaluated in clinical studies. Activated
    charcoal reduces absorption of apixaban thereby lowering apixaban plasma
    concentrations.
  *Prosthetic Heart Valves: The safety and efficacy of ELIQUIS has not been
    studied in patients with prosthetic heart valves and is not recommended in
    these patients.

ADVERSE REACTIONS

The most common and most serious adverse reactions reported with ELIQUIS
(apixaban) were related to bleeding.

DISCONTINUATIONS FOR SURGERY AND OTHER INTERVENTIONS

ELIQUIS should be discontinued at least 48 hours prior to elective surgery or
invasive procedures with a moderate or high risk of unacceptable or clinically
significant bleeding. ELIQUIS should be discontinued at least 24 hours prior
to elective surgery or invasive procedures with a low risk of bleeding or
where the bleeding would be noncritical in location and easily controlled.

DRUG INTERACTIONS

  *Strong Dual Inhibitors of CYP3A4 and P-gp: Inhibitors of CYP3A4 and P-gp
    increase exposure to apixaban and increase the risk of bleeding. Decrease
    the dose of ELIQUIS to 2.5 mg twice daily when coadministered with drugs
    that are strong dual inhibitors of CYP3A4 and P-gp, (e.g., ketoconazole,
    itraconazole, ritonavir, or clarithromycin). In patients already taking
    ELIQUIS at a dose of 2.5 mg daily, avoid coadministration with strong dual
    inhibitors of CYP3A4 and P-gp.
  *Strong Dual Inducers of CYP3A4 and P-gp: Inducers of CYP3A4 and P-gp
    decrease exposure to apixaban and increase the risk of stroke. Avoid
    concomitant use of ELIQUIS with strong dual inducers of CYP3A4 and P-gp
    (e.g., rifampin, carbamazepine, phenytoin, St. John’s wort) because such
    drugs will decrease exposure to apixaban.
  *Anticoagulants and Antiplatelet Agents: Coadministration of antiplatelet
    agents, fibrinolytics, heparin, aspirin, and chronic NSAID use increases
    the risk of bleeding.

PREGNANCY CATEGORY B

There are no adequate and well-controlled studies of ELIQUIS in pregnant
women. Treatment is likely to increase the risk of hemorrhage during pregnancy
and delivery. ELIQUIS should be used during pregnancy only if the potential
benefit outweighs the potential risk to the mother and fetus.

INDICATION

ELIQUIS is indicated to reduce the risk of stroke and systemic embolism in
patients with nonvalvular atrial fibrillation.

Please see full Prescribing Information including BOXED WARNING and Medication
Guide available at www.bms.com.

About the Bristol-Myers Squibb/Pfizer Collaboration

In 2007, Pfizer and Bristol-Myers Squibb entered into a worldwide
collaboration to develop and commercialize ELIQUIS, an investigational oral
anticoagulant discovered by Bristol-Myers Squibb. This global alliance
combines Bristol-Myers Squibb's long-standing strengths in cardiovascular drug
development and commercialization with Pfizer’s global scale and expertise in
this field.

About Bristol-Myers Squibb

Bristol-Myers Squibb is a global biopharmaceutical company whose mission is to
discover, develop and deliver innovative medicines that help patients prevail
over serious diseases. For more information, please visit http://www.bms.com
or follow us on Twitter at http://twitter.com/bmsnews.

Pfizer Inc.: Working together for a healthier world™

At Pfizer, we apply science and our global resources to improve health and
well-being at every stage of life. We strive to set the standard for quality,
safety and value in the discovery, development and manufacturing of medicines
for people and animals. Our diversified global health care portfolio includes
human and animal biologic and small molecule medicines and vaccines; as well
as many of the world’s best-known consumer products. Every day, Pfizer
colleagues work across developed and emerging markets to advance wellness,
prevention, treatments and cures that challenge the most feared diseases of
our time. Consistent with our responsibility as the world’s leading
biopharmaceutical company, we also collaborate with health care providers,
governments and local communities to support and expand access to reliable,
affordable health care around the world. Formore than 150 years,Pfizer has
worked to makea difference for all who rely on us.

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 ELIQUIS will become a commercially successful product.
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, 2011, in our Quarterly Reports on Form 10-Q and our Current Reports on
Form 8-K. Bristol-Myers Squibb undertakes no obligation to publicly update any
forward-looking statement, whether as a result of new information, future
events or otherwise.

PFIZER DISCLOSURE NOTICE:

The information contained in this release is as of January 2, 2013. Pfizer
assumes no obligation to update forward-looking statements contained in this
release as the result of new information or future events or developments.

This release contains forward-looking information about ELIQUIS (apixaban)
that involves substantial risks and uncertainties. Such risks and
uncertainties include, among other things, (i) the uncertainties regarding the
commercial success of ELIQUIS in the U.S. for the reduction of the risk of
stroke and systemic embolism in patients with nonvalvular atrial fibrillation;
(ii) the ability to meet the anticipated timing for the availability of
Eliquis in the U.S.; (iii) decisions by regulatory authorities in
jurisdictions in which applications are pending or may be filed for ELIQUIS
for the prevention of stroke and systemic embolism in patients with
nonvalvular atrial fibrillation regarding whether and when to approve such
applications, as well as their decisions regarding labeling and other matters
that could affect the availability or commercial potential of that indication
in such jurisdictions; and (iv) competitive developments.

A further description of risks and uncertainties can be found in Pfizer’s
Annual Report on Form 10-K for the fiscal year ended December 31, 2011 and in
its reports on Form 10-Q and Form 8-K.

This press release has an accompanying Smart Marketing Page providing further
details about the organization, products and services introduced above. You
can access the Smart Marketing Page via the following link:
http://smp.newshq.businesswire.com/pages/eliquis-apixaban-tablets-now-approved

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Contact:

Bristol-Myers Squibb
Laura Hortas, 609-252-4587 (Media)
laura.hortas@bms.com
or
Ranya Dajani, 609-252-5330 (Investors)
ranya.dajani@bms.com
or
Ryan Asay, 609-252-5020 (Investors)
ryan.asay@bms.com
or
Pfizer Inc.
MacKay Jimeson, 212-733-2324 (Media)
macKay.jimeson@pfizer.com
or
Charles Triano, 212-733-3901 (Investors)
Charles.E.Triano@pfizer.com
 
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