Squibb Company (NYSE:BMY) and Pfizer
Inc. (NYSE:PFE) today announced results of a pre-specified secondary
analysis of the Eliquis Phase 3 AMPLIFY-EXT trial (Apixaban
after the initial Management of PuLmonary embolIsm
and deep vein thrombosis with First-line therapY-EXTended
Treatment). The analysis evaluated clinical and demographic predictors
of all-cause hospitalization in patients with VTE, which includes deep
vein thrombosis (DVT) and pulmonary embolism (PE). Results from this
analysis demonstrated that during the 12-month extended treatment of
VTE, Eliquis significantly reduced the risk of hospitalization
versus placebo. This effect was independent of other variables including
renal function, the only other significant predictor of hospitalization
in the AMPLIFY-EXT population. These data were presented during an oral
session today in Barcelona, Spain, at the ESC Congress 2014.
“The results of this AMPLIFY-EXT secondary analysis showed that Eliquis
significantly reduced the risk of hospitalization,
irrespective of other variables,” said Dr. Alexander T. Cohen, study
investigator and consultant physician, Department of Hematology, Guy’s
and St. Thomas’ Hospitals, King’s College, London. “The findings from
this secondary analysis provide additional support for extended
anticoagulation with Eliquis in VTE patients.”
AMPLIFY-EXT was a randomized, double-blind, placebo-controlled extended
treatment superiority study with 12 months of treatment plus one month
follow-up in patients with VTE who completed six to 12 months of
anticoagulation therapy. The secondary analysis presented today showed
that, compared with placebo, Eliquis 2.5 mg (p=0.032) and 5 mg
(p=0.004) were both associated with significant reduction in all-cause
hospitalization. Of the 2,486 patients included in the AMPLIFY-EXT
trial, 138 patients were hospitalized at least once, including 62
(7.48%) in the placebo group (n=829), 42 (5.00%) in the Eliquis
2.5 mg group (n=840), and 34 (4.18%) in the Eliquis 5 mg group
(n=813). Of the first hospitalizations in the placebo group,
a total of 32 (51.6%) were attributed to VTE recurrence versus six
(17.7%) in the Eliquis 5 mg group and 11 (26.2%) in the Eliquis
2.5 mg group.
The following factors were clinically significant and independent
predictors of all-cause hospitalization during the trial:
Eliquis 2.5 mg versus placebo (HR=0.65, 95% CI=0.43-0.96)
Eliquis 5 mg versus placebo (HR=0.54, 95% CI=0.36-0.83)
Severe or moderate renal impairment versus normal renal function
(HR=2.26, 95% CI=1.30-3.92).
Sex, age, baseline body weight and type of VTE did not significantly
A total of 14 Bristol-Myers Squibb/Pfizer alliance-sponsored abstracts,
including the AMPLIFY-EXT pre-specified secondary analysis described
above, were accepted for presentation at the ESC Congress 2014.
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 prevention of VTE 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. Eliquis is approved
for the treatment of DVT and PE, and prevention of recurrent DVT and PE
following initial therapy in the United States and European Union.
ELIQUIS Important Safety Information
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.
ELIQUIS is indicated for the treatment of DVT and PE, and to reduce the
risk of recurrent DVT and PE following initial therapy.
Important Safety Information
WARNING: (A) PREMATURE DISCONTINUATION OF ELIQUIS INCREASES THE
RISK OF THROMBOTIC EVENTS, (B) SPINAL/EPIDURAL HEMATOMA
(A) Premature discontinuation of any oral anticoagulant,
including ELIQUIS, increases the risk of thrombotic events. If
anticoagulation with ELIQUIS is discontinued for a reason other
than pathological bleeding or completion of a course of therapy,
consider coverage with another anticoagulant.
(B) Epidural or spinal hematomas may occur in patients treated
with ELIQUIS who are receiving neuraxial anesthesia or undergoing
spinal puncture. These hematomas may result in long-term or
permanent paralysis. Consider these risks when scheduling patients
for spinal procedures. Factors that can increase the risk of
developing epidural or spinal hematomas in these patients include:
use of indwelling epidural catheters
concomitant use of other drugs that affect hemostasis, such
as nonsteroidal anti-inflammatory drugs (NSAIDs), platelet
inhibitors, other anticoagulants
a history of traumatic or repeated epidural or spinal
a history of spinal deformity or spinal surgery
optimal timing between the administration of ELIQUIS and
neuraxial procedures is not known
Monitor patients frequently for signs and symptoms of
neurological impairment. If neurological compromise is noted,
urgent treatment is necessary.
Consider the benefits and risks before neuraxial intervention
in patients anticoagulated or to be anticoagulated.
Active pathological bleeding
Severe hypersensitivity reaction to ELIQUIS (e.g., anaphylactic
WARNINGS AND PRECAUTIONS
Increased Risk of Thrombotic Events after Premature
Discontinuation: Premature discontinuation of any oral
anticoagulant, including 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 atrial fibrillation
patients. If ELIQUIS is discontinued for a reason other than
pathological bleeding or completion of a course of therapy, 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,
Advise patients of signs and symptoms of blood loss and to report
them immediately or go 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.
Spinal/Epidural Anesthesia or Puncture: Patients treated with
Eliquis undergoing spinal/epidural anesthesia or puncture may develop
an epidural or spinal hematoma which can result in long-term or
The risk of these events may be increased by the postoperative use of
indwelling epidural catheters or the concomitant use of medicinal
products affecting hemostasis. Indwelling epidural or intrathecal
catheters should not be removed earlier than 24 hours after the last
administration of ELIQUIS. The next dose of ELIQUIS should not be
administered earlier than 5 hours after the removal of the catheter. The
risk may also be increased by traumatic or repeated epidural or spinal
puncture. If traumatic puncture occurs, delay the administration of
ELIQUIS for 48 hours.
Monitor patients frequently and if neurological compromise is noted,
urgent diagnosis and treatment is necessary. Physicians should consider
the potential benefit versus the risk of neuraxial intervention in
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.
Acute PE in Hemodynamically Unstable Patients or Patients who
Require Thrombolysis or Pulmonary Embolectomy: Initiation of
ELIQUIS is not recommended as an alternative to unfractionated heparin
for the initial treatment of patients with PE who present with
hemodynamic instability or who may receive thrombolysis or pulmonary
The most common and most serious adverse reactions reported with
ELIQUIS 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.
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 ELIQUIS doses greater than 2.5 mg
twice daily, the dose of ELIQUIS should be decreased by 50% when it is
coadministered with drugs that are strong dual inhibitors of CYP3A4
and P-gp (e.g., ketoconazole, itraconazole, ritonavir, or
clarithromycin). For patients receiving 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 and other thromboembolic events.
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
VTE encompasses two serious conditions: 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 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 U.S., the number of adults
with VTE is projected to more than double from 950,000 in 2006 to 1.82
million in 2050. Once a VTE has occurred, approximately 33% of patients
may experience a recurrence within 10 years.
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 http://www.bms.com or
follow us on Twitter at http://twitter.com/bmsnews.
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.
Copyright Business Wire 2014