SOUTH SAN FRANCISCO, Calif.,
Nov. 15, 2019 /PRNewswire/
-- Portola Pharmaceuticals, Inc.® (NASDAQ: PTLA)
today announced that Annals of Emergency Medicine, the
journal of the American College of Emergency Physicians (ACEP),
published a multidisciplinary anticoagulant reversal and
replacement guidance statement. The guidance statement is supported
by literature and consensus definitions to support evaluation and
treatment of the bleeding and nonbleeding patient requiring
emergency invasive procedures.
In the guidance statement, ACEP highlighted Andexxa®
[coagulation factor Xa (recombinant), inactivated-zhzo] as a
first-in-line, U.S. Food and Drug Administration (FDA) approved
reversal agent for patients treated with apixaban or rivaroxaban,
as compared to 4F-PCC, which are highlighted as a second-in-line
option for Factor Xa reversal and recommended for use only if
Andexxa is not available.
"As the number of patients taking Factor Xa inhibitors continues
to grow, it is encouraging that many societies, now including ACEP,
have officially recognized the importance of specific, rapid
anticoagulation reversal when life-threatening bleeding occurs,"
said leading author Christoper W.
Baugh, M.D., M.B.A., Department of Emergency Medicine,
Brigham and Women's Hospital, Boston,
MA. "This new guidance aligns with clinical practice at our
institution, where we are seeing positive clinical outcomes in
patients treated with Andexxa."
A multidisciplinary expert panel of academic and community
physicians defined the consensus recommendations through the
creation and interpretation of a consensus anticoagulation reversal
or replacement decision tree and stepwise guidance framework to aid
the emergency physician's evaluation and management of the bleeding
patient receiving an anticoagulant. The expert panel also reached
agreement on key definitions of life-threatening bleeding, bleeding
at a critical site, and emergency surgery or urgent invasive
procedure to support decision tree interpretation.
"This guidance further exemplifies the breakthrough innovation
of Andexxa and the clinical value of rapidly reversing the
anticoagulant effects of Factor Xa inhibitors rivaroxaban or
apixaban in the event of life-threatening or uncontrolled
bleeding," said Scott Garland,
Portola's president and chief
executive officer. "We are encouraged by ACEP's characterization of
Andexxa as a Tier 1 recommendation 'most aligned with FDA-approved
indications and the highest quality of evidence supporting their
use' as it highlights its potential to benefit thousands of
patients facing life-threatening bleeding associated with the use
of rivaroxaban or apixaban."
The consensus statement is available for reference here:
https://www.annemergmed.com/article/S0196-0644(19)31181-3/fulltext.
About Factor Xa Inhibitor-Related Bleeding
The use of
Factor Xa inhibitors is growing rapidly because of their efficacy
and safety profile compared to enoxaparin and warfarin in
preventing and treating thromboembolic conditions such as stroke,
pulmonary embolism and venous thromboembolism (VTE). This growth
has come with a related increase in the incidence of hospital
admissions and deaths related to bleeding, the major complication
of anticoagulation. In 2017, there were approximately 150,000
hospital admissions attributable to Factor Xa inhibitor-related
bleeding and approximately 2,100 bleeding-related deaths per month
in the U.S.
About Andexxa
Andexxa is a recombinant protein
specifically designed to bind to Factor Xa inhibitors and rapidly
reverse their anticoagulant effect. Andexxa was approved by the FDA
in May 2018 as the first and only antidote indicated for
patients treated with rivaroxaban and apixaban, when reversal of
anticoagulation is needed due to life-threatening or uncontrolled
bleeding. Andexxa received both U.S. Orphan Drug and FDA
Breakthrough Therapy designations and was approved under the FDA's
Accelerated Approval pathway based on the change from baseline in
anti-Factor Xa activity in healthy volunteers.
For additional Important Safety Information and Andexxa's full
Prescribing Information, please
visit http://www.Andexxa.com.
IMPORTANT INFORMATION FOR ANDEXXA [coagulation factor Xa
(recombinant), inactivated-zhzo]
BOXED WARNING: THROMBOEMBOLIC RISKS, ISCHEMIC RISKS, CARDIAC
ARREST AND SUDDEN DEATHS
See full prescribing information for complete boxed
warning
Treatment with Andexxa has been associated with serious and
life‑threatening adverse events, including:
- Arterial and venous thromboembolic events
- Ischemic events, including myocardial infarction and
ischemic stroke
- Cardiac arrest
- Sudden deaths
Monitor for thromboembolic events and initiate
anticoagulation when medically appropriate. Monitor for symptoms
and signs that precede cardiac arrest and provide treatment as
needed.
Indication
Andexxa [coagulation factor Xa
(recombinant), inactivated-zhzo] is indicated for patients
treated with rivaroxaban and apixaban, when reversal of
anticoagulation is needed due to life-threatening or uncontrolled
bleeding.
This indication is approved under accelerated approval based on
the change from baseline in anti-Factor Xa (FXa) activity in
healthy volunteers. An improvement in hemostasis has not been
established. Continued approval for this indication may be
contingent upon the results of studies to demonstrate an
improvement in hemostasis in patients.
Andexxa has not been shown to be effective for, and is not
indicated for, the treatment of bleeding related to any FXa
inhibitors other than apixaban and rivaroxaban.
SELECT IMPORTANT SAFETY INFORMATION
Thromboembolic Risk
Arterial and venous thromboembolic
events, ischemic events, sudden deaths, or events where a
thrombotic event could not be ruled out were observed within 30
days post- Andexxa administration in 33 of the 185 patients
(17.8%) evaluable for safety in the ongoing ANNEXA-4 study. The
median time to these events was six days. Of the 86 patients who
were re-anticoagulated prior to a thrombotic event, 11 (12.7%)
patients experienced a thromboembolic event, ischemic event,
cardiac event or death.
Monitor patients treated with Andexxa for signs and
symptoms of arterial and venous thromboembolic events, ischemic
events, and cardiac arrest. To reduce thromboembolic risk, resume
anticoagulant therapy as soon as medically appropriate following
treatment with Andexxa. No thromboembolic events were observed in
223 healthy volunteers who received Factor Xa inhibitors and were
treated with Andexxa.
The safety of Andexxa has not been evaluated in patients
who experienced thromboembolic events or disseminated intravascular
coagulation within two weeks prior to the life-threatening bleeding
event requiring treatment with Andexxa. Safety of Andexxa also
has not been evaluated in patients who received prothrombin complex
concentrates, recombinant Factor VIIa, or whole blood products
within seven days prior to the bleeding event.
Re-elevation or Incomplete Reversal of Anti-FXa
Activity
The time course of anti-FXa activity following
Andexxa administration was consistent among the healthy
volunteer studies and the ANNEXA-4 study in bleeding patients.
Compared to baseline, there was a rapid and substantial decrease in
anti-FXa activity corresponding to the Andexxa bolus. This
decrease was sustained through the end of the
Andexxa continuous infusion. Following the infusion, there was
an increase in anti-FXa activity, which peaked four hours after
infusion in ANNEXA-4 subjects. After this peak, the anti-FXa
activity decreased at a rate similar to the clearance of the FXa
inhibitors.
Thirty-eight patients who were anticoagulated with apixaban had
baseline levels of anti-FXa activity > 150 ng/mL. Nineteen of
these 38 (50%) patients experienced a > 93% decrease from
baseline anti-FXa activity after administration of Andexxa. Eleven
patients who were anticoagulated with rivaroxaban had baseline
anti-FXa activity levels > 300 ng/mL. Five of the 11 patients
experienced a > 90% decrease from baseline anti-FXa activity
after administration of Andexxa.
Adverse Reactions
The most common adverse reactions (≥
5%) in patients receiving Andexxa were urinary tract infections and
pneumonia.
The most common adverse reactions (≥ 3%) in healthy volunteers
treated with Andexxa were infusion-related reactions.
Immunogenicity
As with all therapeutic proteins, there
is potential for immunogenicity. Low titers of anti-Andexxa
antibodies were observed in 26/145 healthy subjects (17%); 6%
(9/145) were first observed at Day 30 with 20 subjects (14%) still
having titers at the last time point (days 44 to 48). To date, the
pattern of antibody response in patients in the ANNEXA-4 study has
been similar to that observed in healthy volunteers with 6% of the
patients having antibodies against Andexxa (6/98 patients). None of
these anti-Andexxa antibodies were neutralizing. No antibodies
cross-reacting with FX or FXa were detected in healthy subjects
(0/145) or in bleeding patients to date (0/98).
About Portola Pharmaceuticals, Inc.
Portola
Pharmaceuticals is a global, commercial-stage
biopharmaceutical company focused on the discovery, development and
commercialization of novel therapeutics that could significantly
advance the fields of thrombosis and other hematologic conditions.
The Company's first two commercialized products are
Andexxa® [coagulation factor Xa (recombinant),
inactivated-zhzo], marketed in Europe as
Ondexxya® (andexanet alfa), and
Bevyxxa® (betrixaban). The company also is
advancing cerdulatinib, a SYK/JAK inhibitor being developed for the
treatment of hematologic cancers. Founded in 2003
in South San Francisco, California, Portola has
operations in the United States and Europe.
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 projected growth in the addressable patient
population for Andexanet and the potential benefit of Andexxa.
Risks that contribute to the uncertain nature of the
forward-looking statements include: the risk that physicians,
patients and payers may not see the benefits of utilizing Andexxa
for the indications for which it is approved; our ability to
continue to manufacture our products and to expand approved
manufacturing facilities; the possibility of unfavorable results
from additional clinical trials involving Andexxa; our ability to
grow our commercial operations in the EU and generate product
revenue within projected timelines and budget; the risk that we may
not obtain additional regulatory approvals necessary to expand or
maintain approved indications for Andexxa; our expectation that we
will incur losses for the foreseeable future and will need
additional funds to finance our operations; the accuracy of our
estimates regarding expenses and capital requirements; our ability
to successfully build a hospital-based sales force and commercial
infrastructure; our ability to obtain and maintain intellectual
property protection for our product candidates; our ability to
retain key scientific or management personnel and general market
conditions. These and other risks and uncertainties are described
more fully in our most recent filings with the Securities and
Exchange Commission, including our 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. We
undertake no obligation to update such statements to reflect events
that occur or circumstances that exist after the date on which they
were made.
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