Eliquis® (apixaban) Receives CHMP Positive Opinion for the Treatment of Deep Vein Thrombosis (DVT) and Pulmonary Embolism (PE),

  Eliquis® (apixaban) Receives CHMP Positive Opinion for the Treatment of Deep
  Vein Thrombosis (DVT) and Pulmonary Embolism (PE), and Prevention of
  Recurrent DVT and PE

Business Wire

PRINCETON, N.J. & NEW YORK -- June 27, 2014

Bristol-Myers Squibb Company (NYSE:BMY) and Pfizer Inc. (NYSE:PFE) today
announced that the Committee for Medicinal Products for Human Use (CHMP) of
the European Medicines Agency (EMA) has adopted a positive opinion
recommending that Eliquis (apixaban) be granted marketing authorization for
the treatment of DVT (deep vein thrombosis) and PE (pulmonary embolism), and
the prevention of recurrent DVT and PE, in adults. The CHMP’s positive opinion
will now be reviewed by the European Commission (EC). The decision on whether
to approve Eliquis for this indication will be made by the EC and will be
applicable to all European Union member states plus Iceland and Norway.

The positive opinion was based on the results from the pivotal AMPLIFY and
AMPLIFY-EXT studies. AMPLIFY (Apixaban for the initial Management of PuLmonary
embolIsm and deep vein thrombosis as First-line therapY), a randomized,
double-blind, multicenter trial, included 5,395 patients (2,691 were
randomized to Eliquis and 2,704 were randomized to standard of care, which was
initial enoxaparin treatment overlapped by warfarin therapy) with confirmed
symptomatic DVT or PE requiring treatment for six months, and evaluated
Eliquis therapy compared to standard of care. The primary efficacy endpoint
was the composite endpoint of recurrent symptomatic VTE (nonfatal DVT or
nonfatal PE) or VTE-related death. The primary safety endpoint was the
incidence of major bleeding compared to standard of care.

AMPLIFY-EXT (Apixaban after the initial Management of PuLmonary embolIsm and
deep vein thrombosis with First-line therapY-EXTended Treatment), a
randomized, double-blind, multicenter trial, included 2,486 patients (842 were
randomized to Eliquis 2.5 mg, 815 were randomized to Eliquis 5 mg and 829 were
randomized to placebo) with prior VTE who had completed six to 12 months of
anticoagulation treatment for DVT or PE, and evaluated Eliquis therapy
compared to placebo. The primary efficacy endpoint was reduction of the
composite of symptomatic, recurrent VTE and death from any cause. The primary
safety endpoint was the incidence of major bleeding.


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.

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

About DVT and PE

Venous thromboembolism, or VTE, encompasses two serious conditions: deep vein
thrombosis (DVT), a blood clot in a deep vein, usually in the lower leg,
thigh, or pelvis, which partially or totally blocks the flow of blood; and
pulmonary embolism (PE), a blood clot that blocks one or more vessels in the
lungs. Approximately one million patients in the EU are diagnosed every year
with VTE. In the US, the number of adults with VTE is projected to more than
double from 0.95 million in 2006 to 1.82 million in 2050. Once a VTE has
occurred, up to 10 percent of people may have a VTE reoccurrence, which could
potentially be fatal.

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 in the
United States, European Union, Japan and a number of other countries around
the world. Eliquis is approved for the prophylaxis of DVT which can lead to PE
in adult patients who have undergone elective hip or knee replacement surgery
in the United States, European Union and a number of other countries around
the world. Eliquis is not approved for this indication in Japan.

About the Bristol-Myers Squibb/Pfizer Collaboration

In 2007, Pfizer and Bristol-Myers Squibb entered into a worldwide
collaboration to develop and commercialize apixaban, 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 www.bms.com.

About 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 Eliquis will receive approval for these additional
indications or, if approved, that these additional indications will lead to
increased commercial success. 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
June 27, 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 that involves substantial
risks and uncertainties about Eliquis’s (apixaban’s) potential benefits and
about potential additional indications for Eliquis in the EU for the treatment
of deep vein thrombosis (DVT) and pulmonary embolism (PE) and the prevention
of recurrent DVT and PE in adults (the “potential additional indications”).
Such risks and uncertainties include, among other things, (i) whether and when
the European Commission (the “EC”) may approve the marketing authorization
application for the potential additional indications, as well as the EC’s
decisions regarding labeling and other matters that could affect the
availability or commercial potential of thepotential additional indications;
(ii) the uncertainties regarding the commercial success of the potential
additional indications in the EU; 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 subsequent reports on Form 10-Q and Form 8-K.

Contact:

Bristol-Myers Squibb
Media:
Shelly Mittendorf, 609-480-2951
shelly.mittendorf@bms.com
or
Investors:
Ranya Dajani, 609-252-5330
ranya.dajani@bms.com
or
Ryan Asay, 609-252-5020
ryan.asay@bms.com
or
Pfizer Inc.
Media:
Jennifer Kokell, 212-733-2596
jennifer.kokell@pfizer.com
or
Investors:
Ryan Crowe, 212-733-8160
ryan.crowe@pfizer.com
 
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