Portola Pharmaceuticals (Nasdaq:PTLA) today announced that it has
initiated a Phase 3 study of andexanet alfa, the company's
investigational Factor Xa inhibitor reversal agent. The study will
evaluate the safety and efficacy of andexanet alfa with
Bristol-Myers Squibb Company (NYSE: BMY) and Pfizer Inc.'s (NYSE:
PFE) Factor Xa inhibitor Eliquis® (apixaban). Portola is developing
andexanet alfa, an FDA-designated breakthrough therapy, as a
potential first-in-class antidote to reverse the anticoagulation
activity of Factor Xa inhibitor-treated patients who are suffering
a major bleeding episode or who require emergency surgery. The
Company is pursuing an Accelerated Approval pathway for andexanet
alfa, which is the only agent that has demonstrated reversal of the
anticoagulation activity of Factor Xa inhibitors as measured by
biomarkers, including anti-Factor Xa activity, in human studies.
"The initiation of our first Phase 3 study for andexanet alfa
represents a significant milestone in the clinical development of
this innovative drug to address the important unmet medical need
for a Factor Xa inhibitor antidote," said John C. Curnutte, M.D.,
Ph.D., executive vice president, research and development at
Portola. "We are strategically focused on using biomarker and
genetic approaches in our clinical development programs to identify
the patients who will most likely benefit from our products and
potentially accelerate their approval. For this Phase 3 study, we
are using biomarker endpoints that have been agreed to with the FDA
to support potential Accelerated Approval for the reversal of
Factor Xa inhibitor anticoagulation. We expect to report initial
data from the first part of the study, in which andexanet alfa is
administered as a bolus infusion, in the fourth quarter of this
year, followed by bolus-plus-continuous infusion data from the
second part of the study in early 2015."
Phase 3 Study Design
The randomized, double-blind, placebo-controlled Phase 3 study
is designed to evaluate the efficacy of andexanet alfa in reversing
Eliquis-induced anticoagulation rapidly after an IV bolus and
sustaining that effect through a continuous infusion. The study
will evaluate the efficacy of andexanet alfa in older healthy
volunteers (ages 50-75 years) as demonstrated by biomarker
endpoints, including anti-Factor Xa levels, plasma free fraction of
the anticoagulant and thrombin generation. In the first part of the
study, approximately 32 healthy volunteers will be given Eliquis 5
mg twice daily and then randomized in a 3:1 ratio to andexanet alfa
administered as a 400 mg IV bolus or to placebo. In the
second part of the study, approximately 32 healthy volunteers will
be randomized in a 3:1 ratio to andexanet alfa administered as a
400 mg IV bolus followed by a continuous infusion of 480 mg at 4
mg/min for 120 minutes or to placebo. Study participants will be
followed for up to 43 days to assess safety.
About the Need for a Factor Xa Inhibitor Reversal
Agent
Currently, millions of patients are treated with Factor Xa
inhibitors for short-term use or chronic conditions, and the
anticoagulant market is expected to continue to grow. Clinical
trial results suggest that, annually, between 1-4 percent of
patients treated with Factor Xa inhibitors may experience major
bleeding, and an additional 1 percent may require emergency
surgery, depending on the patient's underlying medical condition.
Development of an agent specifically designed to reverse the
activity of Factor Xa inhibitors may provide an important treatment
option for patients who experience a major bleeding event or
require emergency surgery.
About Andexanet Alfa
Andexanet alfa is a first-in-class recombinant, modified Factor
Xa molecule being developed as a direct reversal agent for patients
receiving a Factor Xa inhibitor who suffer a major bleeding episode
or who may require emergency surgery. Andexanet alfa acts as a
Factor Xa decoy that targets and sequesters with high specificity
both direct and indirect Factor Xa inhibitors in the blood. Once
bound, the Factor Xa inhibitors are unable to bind to and inhibit
native Factor Xa, thus allowing for the restoration of normal
hemostatic processes.
Results from two Phase 2 proof-of concept studies demonstrated
that andexanet alfa immediately reversed the anti-Factor Xa
activity of Eliquis and XARELTO® (rivaroxaban) in healthy
volunteers. Andexanet alfa provided temporary reversal through the
administration of an IV bolus infusion or sustained reversal with
the addition of an extended infusion. In clinical practice,
patients with bleeding due to a traumatic injury may require
short-acting reversal of their anticoagulant, while those who need
emergency surgery may require long-acting reversal. Andexanet alfa
has the potential to address numerous clinical scenarios by
allowing for flexible and controlled reversal. Andexanet alfa has
been shown to be well tolerated in clinical studies, which have
included more than 90 volunteers, with no thrombotic events,
serious adverse events or antibodies to Factor Xa or Factor X
observed.
Additional Phase 2 proof-of-concept studies with the direct
Factor Xa inhibitors betrixaban and Savaysa™ (edoxaban) and the
indirect Factor Xa inhibitor enoxaparin are either planned or
ongoing.
Earlier this year, Portola and BMS/Pfizer entered into a Phase 3
collaboration that included an upfront payment and provides
additional milestone payments that cover the clinical costs of the
Phase 3 study. Portola retains 100 percent worldwide
decision-making and commercialization rights to andexanet alfa.
Portola and Bayer HealthCare and Janssen Pharmaceuticals Inc. have
a similar Phase 3 collaboration and expect to begin a Phase 3 study
of andexanet alfa with XARELTO in the first half of 2014.
About Portola Pharmaceuticals, Inc.
Portola Pharmaceuticals is a biopharmaceutical company
developing product candidates that have the potential to represent
significant advances in the fields of thrombosis and hematology.
The Company is advancing its three wholly-owned programs using
novel biomarker and genetic approaches that may increase the
likelihood of clinical, regulatory and commercial success of its
first-in-class therapies.
Betrixaban
Portola's lead compound, betrixaban, is an oral, once-daily
Factor Xa inhibitor being evaluated in the only biomarker-based
Phase 3 study for "hospital to home" prophylaxis of venous
thromboembolism (VTE) in acute medically ill patients. Betrixaban's
properties may be particularly suited to potentially demonstrate
efficacy without significantly increasing bleeding in this patient
population. Currently, there is no anticoagulant approved for
extended-duration VTE prophylaxis in acute medically ill
patients.
Andexanet Alfa
Portola's second lead development candidate, andexanet alfa, has
the potential to be a first-in-class reversal agent to reverse the
effects of Factor Xa inhibitors in patients who suffer a major
bleeding episode or who require emergency surgery. Portola has
entered into clinical collaboration agreements with all of the
manufacturers of direct Factor Xa inhibitors, including
Bristol-Myers Squibb and Pfizer (Eliquis® [apixaban]), Bayer
HealthCare and Janssen Pharmaceuticals (XARELTO® [rivaroxaban]),
and Daiichi Sankyo (SavaysaTM [edoxaban]), while retaining all
decision-making and commercial rights to andexanet alfa. Andexanet
alfa has been designated as a Breakthrough Therapy by the U.S. Food
and Drug Administration.
Cerdulatinib* (PRT2070) and PRT2607
Portola's third wholly-owned product candidate, cerdulatinib
(PRT2070), is an orally available molecule that uniquely inhibits
two validated tumor proliferation pathways -- spleen tyrosine
kinase (Syk) and janus kinase (JAK). It is currently being studied
in patients with leukemias or lymphomas with a focus on
genetically-defined subtypes, as well as in patients who have
failed therapy due to relapse or acquired mutations. Portola's
fourth program is partnered with Biogen Idec and is focused on the
development of PRT2607, a selective Syk inhibitor.
For more information, visit www.portola.com and follow the
Company on Twitter @Portola_Pharma.
Forward-looking statement
Statements contained in this press release regarding matters
that are not historical facts are "forward-looking statements"
within the meaning of the Private Securities Litigation Reform Act
of 1995. Because such statements are subject to risks and
uncertainties, actual results may differ materially from those
expressed or implied by such forward-looking statements. Such
statements include, but are not limited to, statements regarding:
Portola's plans for future clinical studies and pursuit of an
Accelerated Approval process for andexanet alfa, anticipated growth
in the market for anticoagulants, clinical trial cost, design and
timing, and the potential efficacy, safety and activity of
andexanet alfa, betrixaban and cerdulatinib. Risks that contribute
to the uncertain nature of the forward-looking statements include:
the accuracy of Portola's estimates regarding its ability to
initiate and/or complete its clinical trials; the success of
Portola's clinical trials and the demonstrated efficacy of
Portola's product candidates thereunder; the accuracy of Portola's
estimates regarding its expenses and capital requirements;
regulatory developments in the United States and foreign countries;
Portola's ability to obtain and maintain intellectual property
protection for its product candidates; and the loss of key
scientific or management personnel. These and other risks and
uncertainties are described more fully in Portola's 2013 Annual
Report on Form 10-K filed with the Securities and Exchange
Commission on March 3, 2014. All forward-looking statements
contained in this press release speak only as of the date on which
they were made. Portola undertakes no obligation to update such
statements to reflect events that occur or circumstances that exist
after the date on which they were made.
*Cerdulatinib is a proposed International Nonproprietary Name
(pINN).
CONTACT: Investor Contact:
Alexandra Santos
Portola Pharmaceuticals
ir@portola.com
650.246.7239
Media Contact:
Joey Fleury
BrewLife
jfleury@brewlife.com
415.946.1090
Portola Pharmaceuticals (NASDAQ:PTLA)
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