FDA Accepts Eliquis® (apixaban) Supplemental New Drug Application for Review for Prophylaxis of Deep Vein Thrombosis Following

  FDA Accepts Eliquis® (apixaban) Supplemental New Drug Application for Review
  for Prophylaxis of Deep Vein Thrombosis Following Hip Or Knee Replacement
  Surgery

Business Wire

PRINCETON, N.J. & NEW YORK -- July 11, 2013

Bristol-Myers Squibb Company (NYSE: BMY) and Pfizer Inc. (NYSE: PFE) today
announced that the U.S. Food and Drug Administration (FDA) has accepted for
review 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 adult patients who have undergone hip or knee replacement
surgery. The Prescription Drug User Fee Act (PDUFA) goal date for a decision
by the FDA is March 15, 2014.

The submission is supported by the ADVANCE-1, ADVANCE-2, and ADVANCE-3
clinical trials, part of the EXPANSE clinical trial program. These trials
randomized nearly 12,000 patients and assessed the safety and efficacy of
Eliquis compared to enoxaparin. ADVANCE-1 and ADVANCE-2 studied patients
undergoing elective total knee replacement, and ADVANCE-3 studied patients
undergoing elective hip replacement.

About VTE

Venous thromboembolism, or VTE, encompasses two serious conditions: deep vein
thrombosis (DVT), a blood clot in a vein, usually in the leg, that partially
or totally blocks the flow of blood; and pulmonary embolism (PE), 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. Patients undergoing major
orthopedic surgery, including total knee or total hip replacement, are at high
risk for VTE. In fact, VTE occurs in 40 to 60 percent of patients undergoing
orthopedic surgery who do not receive preventive care.

About Eliquis^®

Eliquis^® (apixaban) is an oral direct Factor Xa inhibitor. By inhibiting
Factor Xa, a key blood clotting protein, Eliquis prevents 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 (which includes 28 member states plus Iceland
and Norway), Japan and a number of other countries around the world. Eliquis
is approved for prevention of venous thromboembolic events (VTE) in adult
patients who have undergone elective hip or knee replacement surgery in the
European Union (which includes 28 member states plus Iceland and Norway) and a
number of other countries around the world. Eliquis is not approved for this
indication in the U.S.

IMPORTANT SAFETY INFORMATION FOR ELIQUIS

BOXED 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 twice 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. 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 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 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 Eliquis will be approved for this indication in the U.S.
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, 2012, 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 July 11, 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 that involves substantial
risks and uncertainties about a potential additional indication for Eliquis
(apixaban) for the prophylaxis of deep vein thrombosis following hip or knee
replacement surgery (the “additional indication”), including its potential
benefits, that is under review by the FDA. Such risks and uncertainties
include, among other things, (i) whether and when the FDA will approve the
supplemental new drug application for the additional indication, as well as
the FDA’s decisions regarding labeling and other matters that could affect the
availability or commercial potential of the additional indication; (ii) the
uncertainties regarding the commercial success of the additional indication in
the U.S. if it is approved by the FDA; and (iii) competitive developments.

A further description of risks and uncertainties can be found in Pfizer’s
Annual Report on Form 10-K/A for the fiscal year ended December 31, 2012 and
in its reports on Form 10-Q and Form 8-K.

Contact:

Bristol-Myers Squibb
Media:
Chrissy Trank, 609-252-3418, christina.trank@bms.com
Investors:
Ranya Dajani, 609-252-5330, ranya.dajani@bms.com
Ryan Asay, 609-252-5020, ryan.asay@bms.com
or
Pfizer Inc.
Media:
MacKay Jimeson, 212-733-2324, MacKay.Jimeson@pfizer.com
Investors:
Suzanne Harnett, 212-733-8009, Suzanne.Harnett@pfizer.com
 
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