– Expands Patient Access to Andexxa, the First
and Only Antidote for Reversal of the Factor Xa Inhibitors
Rivaroxaban or Apixaban –
Portola Pharmaceuticals, Inc.® (Nasdaq: PTLA) today announced that
the U.S. Food and Drug Administration (FDA) has approved the
Company’s Prior Approval Supplement (PAS) for its large-scale,
second generation Andexxa® [coagulation factor Xa (recombinant),
inactivated-zhzo], allowing for broad commercial launch in the
United States.
Andexxa received both U.S. Orphan Drug and FDA
Breakthrough Therapy designations and was initially approved on May
3, 2018 under the FDA's Accelerated Approval pathway. It is the
first and only antidote indicated for patients treated with
rivaroxaban or apixaban, when reversal of anticoagulation is needed
due to life-threatening or uncontrolled bleeding.
“It is clear from the response to the Andexxa
Early Supply Program that there is significant need for a specific
reversal agent that can address life-threatening bleeding
associated with the use of the Factor Xa inhibitors apixaban and
rivaroxaban,” said Scott Garland, Portola’s president and chief
executive officer. "We are pleased to now be able to stock
hospitals nationwide and serve all patients in the U.S. who could
benefit from the potential life-saving impact of Andexxa.”
The use of Factor Xa inhibitors is rapidly
growing 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
the U.S. alone in 2017, there were approximately 140,000 hospital
admissions attributable to Factor Xa inhibitor-related
bleeding.
The Company will provide additional details on
the commercial launch plans for Andexxa during its annual corporate
webcast scheduled for Tuesday, January 8, at 7:00 a.m. PT (10:00
a.m. ET). The live webcast will be available on the Company's
website at www.portola.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.
IndicationAndexxa [coagulation
factor Xa (recombinant), inactivated-zhzo] is a recombinant
modified human Factor Xa (FXa) protein indicated for patients
treated with rivaroxaban or 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-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.
Limitation of Use 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 or
rivaroxaban.
SELECT IMPORTANT SAFETY
INFORMATION
Thromboembolic and Ischemic
Risk
The thromboembolic and ischemic risks were
assessed in 185 patients who received the Generation 1 product and
in 124 patients who received the Generation 2 product. The median
time to first event was six days, and patients were observed for
these events for 30 days following Andexxa infusion. Of the 86
patients who received Generation 1 product and 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.
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 ActivityThe 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.
The anti-FXa activity returned to the placebo levels approximately
two hours after completion of a bolus or continuous infusion.
Subsequently, the anti-FXa activity decreased at a rate similar to
the clearance of the FXa inhibitors.
Thirty-eight patients who received the
Generation 1 product were anticoagulated with apixaban and 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. Anti-FXa activity levels for
patients who received the Generation 2 product were not
available.
Adverse ReactionsThe 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.
ImmunogenicityAs with all
therapeutic proteins, there is potential for immunogenicity. Using
an electrochemiluminescence (ECL)-based assay, 145 Generation 1
Andexxa-treated healthy subjects were tested for antibodies to
Andexxa as well as antibodies cross-reacting with Factor X (FX) and
FXa. 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% (6/98) of the patients having antibodies
against Andexxa. 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 (0/98)
to date. There is insufficient data to assess for the presence of
anti-Andexxa antibodies for subjects received the Generation 2
product.
Detection of antibody formation is highly
dependent on the sensitivity and specificity of the assay.
Additionally, the observed incidence of antibody (including
neutralizing antibody) positivity in an assay may be influenced by
several factors, including assay methodology, sample handling,
timing of sample collection, concomitant medications, and
underlying disease. For these reasons, comparison of the
incidence of antibodies to Andexxa with the incidence of antibodies
to other products may be misleading.
About Portola Pharmaceuticals,
Inc.Portola Pharmaceuticals is a 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 diseases.
The Company’s two FDA-approved medicines are Andexxa®
[coagulation factor Xa (recombinant), inactivated-zhzo], the first
and only antidote for patients treated with rivaroxaban and
apixaban when reversal of anticoagulation is needed due to
life-threatening or uncontrolled bleeding, and
Bevyxxa® (betrixaban), the first and only oral, once-daily
Factor Xa inhibitor for the prevention of VTE in adult patients
hospitalized for an acute medical illness. The company also is
advancing cerdulatinib, a Syk/JAK inhibitor for the treatment of
hematologic cancers.
Forward-Looking
StatementsStatements 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, our
intention to conduct a broad commercial launch of Andexxa in the
United States and increase patient access to 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 or Bevyxxa for the
indications which they are 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; the risk that the EMA may not
approve Andexxa in the currently anticipated timelines or at all,
and that any marketing approvals or reimbursement limitations may
have significant limitations on its use; the risk that we may not
obtain additional regulatory approvals necessary to expand 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; and our ability to retain key
scientific or management personnel. 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.
Investor Contact:
Cara Miller
Portola PharmaceuticalsIR@portola.com
Media Contact:Julie NormartPure
Communicationsjnormart@purecommunications.com
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