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