SOUTH SAN FRANCISCO, Calif.,
Nov. 6, 2019 /PRNewswire/ -- Portola
Pharmaceuticals, Inc.® (NASDAQ: PTLA) today announced
that new interim results from the Company's ongoing Phase 2a study
of cerdulatinib, an investigational, oral SYK/JAK inhibitor, will
be presented at the 2019 American Society of Hematology (ASH)
Annual Meeting, December 7-10, 2019,
in Orlando, Fla. Presentations
include an oral session featuring data on cerdulatinib in patients
with relapsed/refractory peripheral T-cell lymphoma (PTCL) and
cutaneous T-cell lymphoma (CTCL), as well as a poster highlighting
data in patients with relapsed/refractory follicular lymphoma (FL)
receiving cerdulatinib alone or in combination with rituximab.
The Company will also present new in vitro data on its Factor Xa
inhibitor reversal agent Andexxa [coagulation factor Xa
(recombinant), inactivated-zhzo] (USAN: andexanet alfa) related to
its effect on thrombin generation in bleeding patients, an in vitro
comparison with prothrombin complex concentrates (PCCs), and its
effect on modified anti-Factor Xa (FXa) assays in two oral sessions
and one poster session, respectively.
"We are pleased to present data on two Portola medicines – cerdulatinib and Andexxa –
at the ASH Annual Meeting," said Jeff
Myers, M.D., Portola's
interim chief medical officer. "We look forward to building on the
body of scientific evidence for cerdulatinib as we move toward
initiating our planned registrational trial, CELTIC-1, in patients
with relapsed/refractory peripheral T-cell lymphoma in the coming
months."
Key abstract presentations include:
Oral Presentations
- A Phase 2 Study of the Dual SYK/JAK Inhibitor Cerdulatinib
Demonstrates Good Tolerability and Clinical Response in
Relapsed/Refractory Peripheral T-Cell Lymphoma and Cutaneous T-Cell
Lymphoma (Abstract #466)
Session: 624. Hodgkin Lymphoma and T/NK
Cell Lymphoma—Clinical Studies: Novel Therapies in Peripheral
T-cell Lymphomas
Presenter: Steven M. Horwitz, M.D., Memorial Sloan
Kettering Cancer Center, New York,
NY
Date and Time: Sunday, December 8, 2019, at
12:45 p.m. EST
Location: Orange County Convention Center, Valencia D
(W415D), Level 4
- Effects of Andexanet Alfa on Thrombin Generation in Bleeding
Associated With Factor Xa Inhibitors (Abstract
#711)
Session: 332. Anticoagulation and
Antithrombotic Therapy: Bleeding Outcomes
Presenter: Michiel Coppens, M.D., Ph.D., Amsterdam
University Medical Centers, University of Amsterdam, Amsterdam, Netherlands
Date and Time: Monday, December 9, 2019, at
3:15 p.m. EST
Location: Orange County Convention Center, W414AB,
Level 4
- Prothrombin Complex Concentrates (PCCs) Have Limited Effect
on TF-Initiated Thrombin Generation in FXa Inhibitor-Anticoagulated
Plasma: In Vitro Comparison between Direct Reversal By Andexanet
Alfa and "Work Around" By PCCs (Abstract #713)
Session: 332. Anticoagulation and Antithrombotic
Therapy: Bleeding Outcomes
Presenter: Genmin Lu, M.D., Portola Pharmaceuticals,
Inc., South San Francisco, CA
Date and Time: Monday, December 9, 2019, at
3:45 p.m. EST
Location: Orange County Convention Center, W414AB,
Level 4
Poster Presentations
- Modified Anti-FXa Assays for Measuring the Residual Activity
of Apixaban and Rivaroxaban in Andexanet Alfa-Containing Samples on
the ACL TOP Family Coagulation Analyzers (Abstract
#1153)
Session: 332. Anticoagulation and Antithrombotic
Therapy: Poster I
Presenter: Anuja Khan, Ph.D., Research and Development,
Instrumentation Laboratory, Bedford,
MA
Date and Time: Saturday, December 7,
2019, from 5:30 – 7:30 p.m.
EST
Location: Orange County Convention Center, Hall B,
Level 2
- Rapid and Durable Responses with the SYK/JAK Inhibitor
Cerdulatinib in a Phase 2 Study in Relapsed/Refractory Follicular
Lymphoma—Alone or in Combination with Rituximab (Abstract
#3981)
Session: 623. Mantle Cell, Follicular, and Other
Indolent B-Cell Lymphoma—Clinical Studies: Poster III
Presenter: Paul A. Hamlin, M.D., medical director for the David
H. Koch Center for Cancer Care at Memorial Sloan Kettering Cancer
Center
Date and Time: Monday, December 9, 2019, from 6:00 –
8:00 p.m. EST
Location: Orange County Convention Center, Hall B,
Level 2
Full session details and presentation listings for ASH 2019 are
available at:
https://ash.confex.com/ash/2019/webprogram/start.html.
About Cerdulatinib
Cerdulatinib is an investigational oral, dual spleen tyrosine
kinase (SYK) and janus kinase (JAK) inhibitor that uniquely
inhibits two key cell signaling pathways implicated in certain
hematologic malignancies and autoimmune diseases. There is a strong
rationale for inhibiting both SYK (B-cell receptor pathway) and JAK
(cytokine receptors) in B-cell malignancies where both targets have
been shown to promote cancer cell growth and survival.
The U.S. Food and Drug Administration granted cerdulatinib
Orphan Drug Designation for the treatment of PTCL in September 2018.
IMPORTANT SAFETY 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
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
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. 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 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. 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.
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
Portola's long-term strategy to
build awareness of the clinical data supporting Andexxa, and become
the standard of care for the patients taking Factor Xa inhibitors
who may require a reversal agent 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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SOURCE Portola Pharmaceuticals, Inc.®