U.S. FDA Approves Eliquis® (apixaban) To Reduce The Risk Of Blood Clots Following Hip Or Knee Replacement Surgery

  U.S. FDA Approves Eliquis® (apixaban) To Reduce The Risk Of Blood Clots
  Following Hip Or Knee Replacement Surgery

Business Wire

PRINCETON, N.J. & NEW YORK -- March 14, 2014

Bristol-Myers Squibb Company (NYSE: BMY) and Pfizer Inc. (NYSE: PFE) today
announced that the U.S. Food and Drug Administration (FDA) approved a
Supplemental New Drug Application (sNDA) for Eliquis (apixaban) for the
prophylaxis of deep vein thrombosis (DVT), which may lead to pulmonary
embolism (PE), in patients who have undergone hip or knee replacement surgery.

“Today’s FDA approval of Eliquis for DVT prophylaxis in patients who have
undergone hip or knee replacement is a significant milestone for this
important medicine, which is also approved to reduce the risk of stroke and
systemic embolism in patients with nonvalvular atrial fibrillation,” said
Brian Daniels, M.D., senior vice president, global development and medical
affairs, Bristol-Myers Squibb. “This approval reflects the continued
commitment of the alliance to deliver new treatment options for patients and
physicians.”

“As the number of hip and knee replacement surgeries performed in the U.S.
continues to increase, the risk of DVT following these surgeries remains a
concern for physicians,” said Steven J. Romano, M.D., senior vice president
and Medicines Development Group Head, Global Innovative Pharmaceuticals
Business, Pfizer Inc. “Eliquis provides patients and physicians with a new
treatment option that offers twice daily oral dosing and no routine
coagulation testing, and is broadly accessible through hospitals and managed
health care formularies.”

The full Prescribing Information for Eliquis includes Boxed Warnings for the
increased risk of stroke in patients with nonvalvular atrial fibrillation who
discontinue Eliquis without adequate continuous anticoagulation; and for the
increased risk of epidural or spinal hematoma, which may cause long-term or
permanent paralysis, in patients using Eliquis and undergoing spinal epidural
anesthesia or spinal puncture. Please see complete Boxed Warnings and
additional Important Safety Information in this press release.

DVT, a blood clot that forms in a large vein, usually in the lower leg, thigh,
or pelvis, can lead to PE when a portion or all of a blood clot breaks off and
travels to the lungs, blocking one or more blood vessels. PE can lead to
sudden death.

Based on recent data, each year in the U.S. an estimated 719,000 total knee
replacement surgeries and 332,000 hip replacement surgeries are performed.
Patients undergoing hip or knee replacement surgery without thromboprophylaxis
are at risk for developing DVT and PE. ^ Guidelines recommend the use of
anticoagulants for the prophylaxis of DVT and PE for most patients undergoing
orthopedic surgery.

“DVT, which may lead to PE, is a serious medical condition,” ^ said Richard J.
Friedman, M.D., FRCSC, Professor of Orthopaedic Surgery, Medical University of
South Carolina. “The FDA approval of Eliquis gives U.S. orthopedic surgeons a
new option for DVT prophylaxis in both hip and knee replacement surgery.”

This sNDA approval for Eliquis is supported by three clinical trials (the
ADVANCE clinical trial program). The ADVANCE trials randomized more than
11,000 patients, with 5,770 receiving Eliquis and 5,755 receiving enoxaparin,
to assess the safety and efficacy of Eliquis.

In December 2013, the FDA accepted for review another sNDA for Eliquis for the
treatment of DVT and PE, and for the reduction in the risk of recurrent DVT
and PE.

INDICATION

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

ELIQUIS is indicated for the prophylaxis of deep vein thrombosis (DVT), which
may lead to pulmonary embolism (PE), in patients who have undergone hip or
knee replacement surgery.

IMPORTANT SAFETY INFORMATION

WARNINGS: (A) DISCONTINUING ELIQUIS IN PATIENTS WITH NONVALVULAR ATRIAL
FIBRILLATION WITHOUT ADEQUATE CONTINUOUS ANTICOAGULATION INCREASES RISK OF
STROKE, (B) SPINAL/EPIDURAL HEMATOMA

(A) 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.

(B) When neuraxial anesthesia (epidural/spinal anesthesia) or spinal puncture
is employed, patients anticoagulated or scheduled to be anticoagulated with
low molecular weight heparins, heparinoids, or Factor Xa inhibitors for
prevention of thromboembolic complications are at risk of developing an
epidural or spinal hematoma which can result in long-term or permanent
paralysis.

The risk of these events may be increased by the use of indwelling epidural
catheters for administration of analgesia or by the concomitant use of drugs
affecting hemostasis such as nonsteroidal anti-inflammatory drugs (NSAIDs),
platelet aggregation inhibitors, or other anticoagulants. The risk also
appears to be increased by traumatic or repeated epidural or spinal puncture.

Monitor patients for signs and symptoms of neurologic impairment. If
neurologic compromise is noted, urgent treatment is necessary. Consider the
potential benefit versus risk before neuraxial intervention in patients
anticoagulated or to be anticoagulated for thromboprophylaxis.

CONTRAINDICATIONS

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

WARNINGS AND PRECAUTIONS

  *Increased Risk of Stroke with Discontinuation of ELIQUIS in Patients with
    Nonvalvular Atrial Fibrillation: 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 at least 24 hours after the
    last dose (i.e., about two half-lives). A specific antidote for ELIQUIS is
    not available. Hemodialysis does not appear to have a substantial impact
    on apixaban exposure. 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 have 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.

TEMPORARY INTERRUPTION 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.
Bridging anticoagulation during the 24 to 48 hours after stopping ELIQUIS and
prior to the intervention is not generally required. ELIQUIS should be
restarted after the surgical or other procedures as soon as adequate
hemostasis has been established.

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. For
    patients receiving 5 mg twice daily, the dose of ELIQUIS should be
    decreased when it is 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 twice daily, avoid coadministration with strong dual
    inhibitors of CYP3A4 and P-gp.
  *Strong Dual Inducers of CYP3A4 and P-gp: 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 and increase the risk of stroke.
  *Anticoagulants and Antiplatelet Agents: Coadministration of antiplatelet
    agents, fibrinolytics, heparin, aspirin, and chronic NSAID use increases
    the risk of bleeding. APPRAISE-2, a placebo-controlled clinical trial of
    apixaban in high-risk post-acute coronary syndrome patients treated with
    aspirin or the combination of aspirin and clopidogrel, was terminated
    early due to a higher rate of bleeding with apixaban compared to placebo.

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.

About Eliquis

Eliquis (apixaban) is an oral selective Factor Xa inhibitor. By inhibiting
Factor Xa, a key blood clotting protein, Eliquis decreases thrombin generation
and blood clot formation. Eliquis is approved to reduce the risk of stroke and
systemic embolism in patients with nonvalvular atrial fibrillation and for
prophylaxis of DVT, which may lead to PE, in patients who have undergone hip
or knee replacement surgery.

About Deep Vein Thrombosis and Pulmonary Embolism

DVT is a blood clot in a vein, usually in the lower leg, thigh, or pelvis,
which partially or totally blocks the flow of blood. PE is a blood clot
blocking one or more vessels in the lungs. DVT causes multiple symptoms
including pain, swelling, and redness, and more importantly, can progress to
PE, which carries the risk of sudden death.

Please see full Prescribing Information, including BOXED WARNINGS 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 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 bring therapies to
people that extend and significantly improve their lives. We strive to set the
standard for quality, safety and value in the discovery, development and
manufacture of health care products. Our global portfolio includes medicines
and vaccines as well as many of the world's best-known consumer health care
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
one of the world's premier innovative biopharmaceutical companies, we
collaborate with health care providers, governments and local communities to
support and expand access to reliable, affordable health care around the
world. For more than 150 years, Pfizer has worked to make a difference for all
who rely on us. To learn more, please visit us at www.pfizer.com.

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 the approval of these additional indications in the U.S.
will lead to increased commercial success or that ELIQUIS will be approved for
any other additional indications. 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, 2013, 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 March 14, 2014. 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),
including its potential benefits, that involves substantial risks and
uncertainties. Such risks and uncertainties include, among other things, (i)
uncertainty regarding the commercial success of the indication for Eliquis for
the prophylaxis of DVT in patients who have undergone hip or knee replacement
surgery; (ii) whether and when ELIQUIS may be approved by the U.S. Food and
Drug Administration (FDA) for the treatment of DVT and PE and for the
reduction in the risk of recurrent DVT and PE, as well as the FDA's decisions
regarding labeling and other matters that could affect the availability or
commercial potential of that additional indication for Eliquis; and (iii)
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, 2013 and in
its reports on Form 10-Q and Form 8-K.

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Contact:

Bristol-Myers Squibb
Shelly Mittendorf (Media)
609-252-5799
shelly.mittendorf@bms.com
or
Ranya Dajani (Investors)
609-252-5330
ranya.dajani@bms.com
or
Ryan Asay (Investors)
609-252-5020
ryan.asay@bms.com
or
Pfizer Inc.
Jennifer Kokell (Media)
917-741-4254
jennifer.kokell@pfizer.com
or
Ryan Crowe (Investors)
212-733-8160
ryan.crowe@pfizer.com
 
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