Portola Pharmaceuticals (Nasdaq:PTLA) today announced the
initiation of a single-arm Phase 4 study to support the approval of
andexanet alfa by the U.S. Food and Drug Administration (FDA) under
an Accelerated Approval pathway. Portola is developing this
FDA-designated breakthrough therapy as a universal antidote for
patients receiving a Factor Xa inhibitor anticoagulant who suffer a
major bleeding episode or who may require emergency surgery.
"We collaborated closely with the FDA on a Phase 4 study design.
The combination of data from our two Phase 3 studies and data from
a small number of patients in this Phase 4 study will serve as the
clinical basis of a Biologics License Application [BLA], which we
plan to submit at the end of 2015 for approval of andexanet alfa
under an Accelerated Approval pathway," said John T. Curnutte,
M.D., Ph.D., executive vice president, research and development for
Portola. "We're pleased with our progress in developing what could
be the first universal Factor Xa inhibitor antidote approved to
help physicians meet the growing unmet medical need of managing the
severe bleeding associated with these new and important oral
anticoagulants. We are developing andexanet alfa to meet the
criteria required by the agency and physicians to become the
standard of care universal reversal agent for Factor Xa
inhibitors."
Design of Phase 4 Study
The open-label, single-arm, Phase 4 study is being conducted in
patients receiving apixaban, rivaroxaban or enoxaparin (a low
molecular weight heparin) who present with an acute major bleed.
Acute major bleeding includes life-threatening bleeding, bleeding
associated with very low blood counts, or bleeding that occurs in a
critical area such as the brain or surrounding the heart. The trial
excludes bleeding due to major trauma and large blood vessel
rupture. Patients will receive andexanet alfa as an intravenous
(IV) bolus followed immediately by a continuous infusion. The study
is evaluating andexanet alfa's ability to decrease anti-Factor Xa
activity and restore hemostasis in patients. Safety endpoints
include overall 45 day safety, including an evaluation of
thrombotic activity and antibody development. The study will be
conducted at over 50 sites in North America and Europe.
About the Need for a Factor Xa Inhibitor
Antidote
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. Recent
patient data(i) confirm earlier clinical trial results showing
that, while most novel anticoagulants have lower bleeding rates
than warfarin, serious bleeding (annually, between 1-4 percent)
could still occur. Development of a specific antidote designed to
reverse the anticoagulant 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 acts as a Factor Xa decoy that targets and
sequesters with high specificity both oral and injectable 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. Andexanet alfa has
the potential to address numerous clinical scenarios where an
antidote is needed by allowing for flexible and controlled
reversal. This can be short-acting through the administration of an
IV bolus or longer-acting with the addition of an extended
infusion.
Andexanet alfa is unique in that it is the only reversal agent
in development that has been demonstrated to immediately and
significantly reverse all of the key pharmacodynamic measurements
of coagulation that have been agreed to with the FDA for
accelerated approval. These include anti-Factor Xa levels, thrombin
generation and unbound anticoagulant levels (free fraction). This
comprehensive reversal has been demonstrated with andexanet alfa in
all of our clinical studies conducted to date using the
Factor Xa inhibitors -- apixaban, rivaroxaban, edoxaban and
enoxaparin.
About the Andexanet Alfa Clinical Development
Program
Portola is evaluating andexanet alfa in randomized,
placebo-controlled Phase 3 ANNEXA™ (Andexanet Alfa a Novel Antidote
to the Anticoagulant Effects of fXA Inhibitors) registration
studies using pharmacodynamic endpoints agreed to with the FDA,
such as anti-Factor Xa inhibitor units, to demonstrate
efficacy.
Portola reported statistically significant results from the
first part of the Phase 3 ANNEXA-A study, which evaluated andexanet
alfa administered as a single IV bolus dose with Bristol-Myers
Squibb Company and Pfizer Inc.'s direct Factor Xa inhibitor
apixaban, and from the first part of the Phase 3 ANNEXA-R study
with Bayer HealthCare and Janssen's direct Factor Xa inhibitor
rivaroxaban. The second parts of the ANNEXA-A and ANNEXA-R studies
are ongoing and are evaluating a bolus plus a continuous infusion
of andexanet alfa to sustain the reversal of anticoagulation
activity. A Phase 4 confirmatory study is also ongoing, of which
data from a small number of patients will be submitted with the
BLA.
Results from four separate Phase 2 proof-of concept studies with
apixaban, rivaroxaban, edoxaban and enoxaparin, a low molecular
weight heparin and indirect Factor Xa inhibitor, in healthy
volunteers demonstrated that andexanet alfa immediately reversed
the anticoagulation activity of each Factor Xa inhibitor and that
the reversal could be sustained. Andexanet alfa has been shown to
be well tolerated in clinical studies, which have included more
than 140 healthy volunteers. No thrombotic events or antibodies to
Factor Xa or Factor X have been observed.
A Phase 2 proof-of-concept study with Portola's investigational
Factor Xa inhibitor betrixaban is planned.
About Portola Pharmaceuticals, Inc.
Portola Pharmaceuticals is a biopharmaceutical company
developing product candidates that could significantly advance the
fields of thrombosis and other hematologic diseases. 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 potentially life-saving
therapies. Portola's partnered program is focused on developing
selective Syk inhibitors for inflammatory conditions.
Betrixaban
Portola's wholly-owned, oral, once-daily Factor Xa inhibitor
betrixaban is 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 distinct
properties may have the potential to allow the agent to demonstrate
efficacy without the significant increase in the rate of major
bleeding that was seen in this patient population with other Factor
Xa inhibitors. If approved, betrixaban could be the first
anticoagulant for both hospital and post-discharge VTE prophylaxis
and the standard of care in this large market of more than 20
million patients in the G7 countries alone.
Andexanet Alfa
Andexanet alfa, a recombinant modified human Factor Xa molecule,
has the potential to be a first-in-class antidote to reverse the
effects of Factor Xa inhibitors in patients who suffer a major
bleeding episode or who require emergency surgery. Andexanet alfa
has been designated as a breakthrough therapy by the U.S. Food and
Drug Administration. Portola has entered into Phase 3 clinical
collaboration agreements with all of the manufacturers of direct
Factor Xa inhibitors – Bristol-Myers Squibb and Pfizer (Eliquis
[apixaban]), Bayer HealthCare and Janssen Pharmaceuticals (XARELTO®
[rivaroxaban]), and Daiichi Sankyo (edoxaban) – while retaining all
commercial rights to andexanet alfa. The Company is currently
evaluating andexanet alfa in the Phase 3 ANNEXA™ (Andexanet Alfa a
Novel Antidote to the Anticoagulant Effects of fXA Inhibitors)
registration studies.
Cerdulatinib (PRT2070)
Portola's product candidate in the area of hematologic cancer,
cerdulatinib, 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
evaluated in a Phase 1/2a proof-of-concept study in patients with B
cell 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.
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, timing of clinical
study results, future regulatory filings and pursuit of an
Accelerated Approval process for andexanet alfa, anticipated growth
in the market for anticoagulants, and the potential efficacy,
safety and activity of Portola's product candidates. 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; Portola's ability to manufacture andexanet alfa;
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 most recent
filings with the Securities and Exchange Commission, including its
Annual Report on Form 10-K and most recent Quarterly Report on Form
10-Q. 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.
(i) Source: Truven MARKETSCAN® Commercial, Medicare
Supplemental and Medicaid Database (12 months ending March
2014)
CONTACT: Media: Joey Fleury,
BrewLife,
jfleury@brewlife.com,
415.946.1090
Investors: Alexandra Santos,
Portola Pharmaceuticals,
ir@portola.com,
650.246.7239
Portola Pharmaceuticals (NASDAQ:PTLA)
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