Portola Pharmaceuticals (Nasdaq:PTLA) today announced topline
results from the first part of the Phase 3 ANNEXA™-R (Andexanet
Alfa a Novel Antidote to the Anticoagulant Effects of FXa
Inhibitors – Rivaroxaban) study, which is evaluating the safety and
efficacy of andexanet alfa with the Factor Xa inhibitor XARELTO®
(rivaroxaban). Results showed that the study met its primary
endpoint with high statistical significance. Andexanet alfa
administered as an intravenous (IV) bolus significantly and
immediately reversed the steady-state anticoagulation activity of
XARELTO® and was well tolerated. The Company expects to present the
full data set at the American College of Cardiology's (ACC) 64th
Annual Scientific Session in San Diego on Monday, March 16 at 11:30
a.m. PT in an oral session titled "Highlighted Original Research:
Acute Coronary Syndromes and the Year in Review." The second part
of the ANNEXA-R study, which is evaluating a bolus plus a
continuous infusion of andexanet alfa to sustain reversal, is
ongoing.
Portola is developing andexanet alfa, a U.S. Food and Drug
Administration (FDA)-designated breakthrough therapy, as a
universal antidote for patients treated with oral and injectable
Factor Xa inhibitors who are experiencing a major bleeding episode
or who require emergency surgery. Andexanet alfa has been studied
in more than 140 volunteers in clinical studies.
"The statistically significant Phase 3 ANNEXA-R study data,
together with results presented previously with apixaban, provide
compelling evidence that this groundbreaking agent could serve as a
universal antidote for Factor Xa inhibitor anticoagulants," said
John T. Curnutte, M.D., Ph.D., executive vice president, research
and development for Portola. "Andexanet alfa is unique among the
other reversal agents in development in that it has been the only
agent 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 (free
fraction). This has been demonstrated with all of the Factor Xa
inhibitors studied to date – apixaban, rivaroxaban, edoxaban and
enoxaparin."
ANNEXA-R Study Design and Results
The randomized, double-blind, placebo-controlled Phase 3
ANNEXA-R study is evaluating the safety and efficacy of andexanet
alfa in reversing XARELTO® -induced anticoagulation in healthy
volunteers ages 50-75 years. Efficacy is being evaluated using
biomarker endpoints, with anti-Factor Xa levels as the primary
endpoint. Secondary endpoints include plasma levels of plasma
unbound (free fraction) of XARELTO® and thrombin generation
levels.
In the first part of the ANNEXA-R study, reported today, 41
healthy volunteers were given XARELTO® 20 mg once daily for four
days and then randomized in a 2:1 ratio to receive at Cmax either
andexanet alfa administered as an 800 mg IV bolus (n=27) or to
placebo (n=14). The study achieved its primary endpoint with high
statistical significance. Results showed that andexanet alfa
significantly and immediately reversed the anticoagulation activity
of XARELTO®. Andexanet alfa was shown to be well tolerated.
In the second part of the ANNEXA-R study, approximately 40
healthy volunteers will be given XARELTO® 20 mg once daily for four
days and will then be randomized in a 2:1 ratio to receive either
andexanet alfa administered as an 800 mg IV bolus followed by a
continuous infusion of 8 mg/min for 120 minutes or to placebo. Data
from this part of the study are expected in mid-2015.
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 datai confirm earlier clinical trial results showing 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. 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 the only compound being studied as a reversal
agent for Factor Xa inhibitors that directly and specifically
corrects anti-Factor Xa activity -- the anticoagulant mechanism of
these agents.
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 intravenous (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.
These studies are designed to support the Company's BLA filing
for Accelerated Approval. As part of the Accelerated Approval
process, a Phase 4 confirmatory patient study evaluating clinical
outcomes with andexanet alfa is planned.
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.
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
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 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 indications, efficacy, safety and
activity of andexanet alfa. 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 for the third quarter of 2014,
which was filed on November 4, 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.
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)
Graphique Historique de l'Action
De Juin 2024 à Juil 2024
Portola Pharmaceuticals (NASDAQ:PTLA)
Graphique Historique de l'Action
De Juil 2023 à Juil 2024