Portola Pharmaceuticals Announces Additional Positive Phase 2 Proof-of-Concept Data for Andexanet Alfa (PRT4445*)
11 Novembre 2013 - 2:00PM
Portola Pharmaceuticals, Inc. (Nasdaq:PTLA) today announced initial
results from a Phase 2 proof-of-concept study of andexanet alfa,
its investigational Factor Xa inhibitor antidote, in healthy
volunteers who were administered the Factor Xa inhibitor XARELTO®
(rivaroxaban). Results from the first two dosing cohorts of the
study demonstrated that andexanet alfa is able to dose-dependently
reverse the anticoagulant effects of XARELTO®. In addition, no
serious adverse events were reported. These data, as well as data
from additional cohorts evaluating higher doses of andexanet alfa,
will be presented in a poster session on December 9, 2013 at the
55th American Society of Hematology (ASH) Annual Meeting and
Exposition, which is being held in New Orleans from December 7-10,
2013.
Andexanet alfa is being developed as a potential first-in-class,
universal antidote for patients who experience an uncontrolled
bleeding episode or who require emergency surgery while being
anticoagulated with a Factor Xa inhibitor. Registration-enabling
studies are planned to begin in 2014 as part of a potential
Accelerated Approval pathway to address the important unmet need
due to a lack of an approved antidote.
"We are pleased with these initial data demonstrating a
dose-dependent reversal of the Factor Xa inhibitor, XARELTO®. These
findings are consistent with what we expect from andexanet's
mechanism of action, and the dose-dependent activity we have seen
with andexanet alfa in our prior Phase 2 study with Eliquis®. We
look forward to presenting data on additional cohorts evaluating
higher doses of andexanet in healthy volunteers treated with
XARELTO® at the ASH meeting in December," said John T. Curnutte,
M.D., Ph.D., executive vice president of research and development
for Portola. "We are now increasingly confident that the positive
proof-of-concept data shown with both Eliquis and XARELTO® to date
will help us determine an appropriate and effective dosing regimen
for all oral Factor Xa inhibitors and enoxaparin for use in the
conduct of our planned pivotal registration studies."
This randomized, placebo-controlled, double-blind, cohort
dose-escalation Phase 2 proof-of-concept study treated healthy
volunteers with an oral dose of XARELTO® at 20 mg qd for 6 days and
then randomized them in a 6:3 ratio to andexanet alfa in different
dosing cohorts. The first two cohorts received a single IV bolus of
andexanet alfa at 210 mg or 420 mg, respectively. Within two
minutes following completion of the 210 mg and 420 mg bolus of
andexanet alfa, anti-Factor Xa activity decreased dose-dependently
by 20 percent and 53 percent, respectively. XARELTO®-induced
inhibition of thrombin generation and prolongation of both
prothrombin time and activated clotting time were also rapidly
reversed by andexanet alfa in a dose-dependent manner. Interim
safety data showed that andexanet alfa was well tolerated, with no
thrombotic events, or serious or severe adverse events reported.
The abstract with these data is currently available on the ASH
website.
Need for Reversal Agent for Factor Xa
Inhibitors Currently, millions of patients are treated
with Factor Xa inhibitors for short-term use or chronic conditions
in the G7 countries, and the anticoagulant market is expected to
continue to grow with the adoption of novel oral anticoagulants.
Clinical trial results suggest that, depending on their underlying
medical condition, annually between 1 and 4 percent of these
patients will experience major bleeding and an additional 1 percent
will require emergency surgery. Based on these data and projected
use of Factor Xa inhibitors, the Company estimates there could be
approximately 500,000 hospital visits each year by patients who
would benefit from an antidote by the year 2020. Currently, there
is no antidote or reversal agent approved for use against Factor Xa
inhibitors. Leading clinicians have identified, and the United
States Food and Drug Administration (FDA) has recognized, the lack
of an effective reversal agent for Factor Xa inhibitors as a
significant unmet medical need.
Andexanet Alfa Clinical Development Program
Portola has entered into clinical collaboration agreements with
all of the manufacturers of currently approved Factor Xa
inhibitors, including Bristol-Myers Squibb and Pfizer (Eliquis®
[apixaban]), Bayer HealthCare and Janssen Pharmaceuticals
(XARELTO® [rivaroxaban]), and Daiichi Sankyo (Lixiana® [edoxaban]),
while retaining all rights to the program. The Company is currently
conducting a series of Phase 2 proof-of-concept studies in healthy
volunteers to evaluate the safety, tolerability, pharmacokinetics
and pharmacodynamics of andexanet alfa after dosing of a direct or
indirect Factor Xa inhibitor, including Eliquis®, XARELTO®,
Lovenox® (enoxaparin), Lixiana® and Portola's investigational oral
Factor Xa inhibitor, betrixaban.
About Andexanet Alfa (PRT4445*)
Andexanet alfa is a novel recombinant, modified Factor Xa
molecule that has the potential to be the first universal antidote
to reverse the effects of Factor Xa inhibitors in patients who
suffer an uncontrolled bleeding episode or require emergency
surgery. Andexanet alfa is similar to native Factor Xa, but has
been modified to restrict its biological activity, such as its
ability to cleave thrombin, an enzyme involved in the clotting
cascade. Andexanet alfa acts as a Factor Xa decoy that binds and
sequesters direct Factor Xa inhibitors in the blood. Once bound to
andexanet alfa, the Factor Xa inhibitors are unable to bind to and
inhibit native Factor Xa. The native Factor Xa should then be
available to participate in the coagulation process and restore
hemostasis.
About Portola Pharmaceuticals, Inc.
Portola Pharmaceuticals is a biopharmaceutical company focused
on the development and commercialization of novel therapeutics in
the areas of thrombosis, other hematologic disorders and
inflammation. Portola's wholly-owned lead compound, betrixaban, is
a novel, oral, once-daily Factor Xa inhibitor in Phase 3
development for extended-duration prophylaxis of a form of
thrombosis known as venous thromboembolism (VTE) in acute medically
ill patients. Currently, there is no anticoagulant approved for
extended-duration VTE prophylaxis in this population. Portola's
second lead development candidate, andexanet alfa (PRT4445*), has
the potential to be the first universal antidote to reverse the
effects of Factor Xa inhibitors in patients who suffer an
uncontrolled bleeding episode or who require emergency surgery.
Portola retains full, worldwide commercial rights to andexanet
alfa. Portola's third product candidate, PRT2070, is an orally
available kinase inhibitor that uniquely inhibits two validated
tumor proliferation pathways -- spleen tyrosine kinase (Syk) and
janus kinase (JAK). It is currently being studied in patients with
genetically-defined hematologic cancers, as well as for 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.
Forward-looking statements
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
andexanet alfa's potential efficacy, safety, duration of activity
and potential to reverse the effects of all Factor Xa inhibitors,
our plans for future clinical studies and pursuit of an Accelerated
Approval process for andexanet alfa and anticipated growth in the
market for anticoagulants. 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 studies; the success of Portola's clinical
studies and the demonstrated efficacy of Portola's product
candidates thereunder; regulatory developments in the United States
and foreign countries; and Portola's ability to attract and retain
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. 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.
*PRT4445 has a proposed International Nonproprietary Name (pINN)
of andexanet alfa.
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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