– Excellent or Good Hemostasis Achieved in 83
Percent of Patients; Thrombotic Events Consistent with High
Background Thrombotic Risk –
Portola Pharmaceuticals, Inc.® (Nasdaq:PTLA) today announced new
interim results from ANNEXA-4, the Company’s ongoing Phase 3b/4
trial of its investigational universal Factor Xa inhibitor antidote
AndexXa® (andexanet alfa) among patients experiencing acute major
bleeding while taking a Factor Xa inhibitor. Interim data from 228
patients (of which 132 were adjudicated for efficacy) showed that
AndexXa rapidly and significantly reversed anti-Factor Xa activity
(the anticoagulant mechanism of these drugs) when administered as a
bolus, and sustained this reversal when followed by a 120-minute
infusion. In addition, 83 percent of these patients achieved
excellent or good hemostasis (stoppage of bleeding) over a 12-hour
period following treatment with AndexXa. Thrombotic events (11
percent) and death rates (12 percent) were consistent with previous
ANNEXA-4 trial results and with the high background thrombotic risk
of the enrolled patient population. Results were presented today in
a Late-Breaking Clinical Trial Session at the American College of
Cardiology’s 67th Annual Scientific Session & Expo (ACC.18).
“These data are particularly compelling when you
consider the high-risk profile of the ANNEXA-4 population, which
includes a substantial number of elderly patients presenting with
intracranial hemorrhage and anticoagulated for venous
thromboembolism, and the lack of any FDA- or EMA-approved reversal
agent for these patients,” said Stuart J. Connolly, M.D., ANNEXA-4
Executive Committee chairman and professor in the Department of
Medicine of the Faculty of Health Sciences at McMaster University
in Hamilton, Ontario. “The interim efficacy and safety data
continue to support the promising role of AndexXa as an antidote to
reverse anticoagulation in Factor Xa-associated bleeding.”
The use of Factor Xa inhibitors is continuing to
grow at a significantly steady pace because of their demonstrated
efficacy in preventing embolic diseases such as stroke and
pulmonary embolism. However, the incidence of hospital admissions
and death related to Factor Xa-inhibitor bleeding is also
increasing. In the U.S. alone, there were approximately 117,000
hospital admissions attributable to Factor Xa-related bleeding in
2016 and more than 2,000 bleeding-related deaths per
month.
“The ANNEXA-4 trial continues to demonstrate
efficacy and safety results that are consistent with that of other
therapies approved for anticoagulant reversal based on a single-arm
study,” said John Curnutte, M.D., Ph.D., executive vice president,
research and development at Portola. “We remain confident in the
potential of AndexXa to address a clear and growing unmet need and
we look forward to sharing these results with the U.S. and European
regulatory authorities as they consider our marketing application
for andexanet alfa.”
The interim results included safety data from 227 of the 228
enrolled patients who experienced intracranial hemorrhage (ICH) (61
percent), gastrointestinal bleeding (27 percent) or bleeding from
another site (11 percent) within 18 hours of administration of
apixaban (117 patients), rivaroxaban (90 patients), enoxaparin (17
patients) or edoxaban (3 patients). Safety data for the one
remaining patient, who was enrolled and active in the study, was
not available at the time of this analysis.
During the 30-day follow-up period, the
thrombotic event rate was 11 percent (n=24) for the entire
population and 12 percent (n=17) among patients experiencing an
ICH. The mortality rate for all patients was 12 percent (n=27). The
rate of these events occurred within the range expected in this
population given the severity of the bleeding, their advanced age
and underlying thrombotic risk, and the percentage who restarted
anticoagulant therapy (57 percent) following their bleeding
episode.
Two of the 228 patients experienced an infusion reaction and
none developed antibodies to Factor Xa or Factor X or neutralizing
antibodies to AndexXa.
Data from the adjudicated efficacy population of 132 patients,
who were confirmed to have major bleeding by the independent
adjudication committee, and whose baseline anti-Factor Xa activity
was substantially elevated (>75 ng/ml or 0.25 IU/mL if receiving
enoxaparin), demonstrate that AndexXa rapidly and substantially
reversed anti-Factor Xa activity, and these levels were sustained
for the duration of administration.
Specifically, anti-Factor Xa activity, the co-primary efficacy
endpoint, decreased by a median of greater than 90 percent for both
apixaban and rivaroxaban following the bolus dose, which was
sustained at similar levels for the duration of the two-hour
infusion.
The independent adjudication committee determined that 109 of
132 patients (83 percent) achieved effective hemostasis, as defined
by a hemostatic efficacy rating of “excellent” or “good” (the
criteria used by the adjudication committee were based on similar
criteria used in a pivotal study of Kcentra®, approved for the
reversal of Vitamin K antagonists). Among patients with
gastrointestinal bleeding, 86 percent had effective hemostasis, as
did 81 percent of patients with intracranial bleeding. Hemostatic
efficacy was similar for patients on apixaban (82 percent) and
rivaroxaban (83 percent).
Portola is developing andexanet alfa as a
universal antidote for patients anticoagulated with an oral or
injectable Factor Xa inhibitor, including apixaban and rivaroxaban,
who experience a serious uncontrolled or life-threatening bleeding
event or who require urgent or emergency surgery. Andexanet alfa is
currently under review by the U.S. Food and Drug Administration
(FDA), with an assigned action date of May 4, 2018, and by the
European Medicines Agency (EMA), with an expected decision in
2019.
ANNEXA-4 Study DesignANNEXA-4 is a global,
single-arm, open-label clinical trial designed to evaluate
andexanet alfa in patients who present with an acute major bleed
while receiving apixaban, rivaroxaban, edoxaban or enoxaparin. This
multi-center, prospective cohort study is not randomized and all
participants receive andexanet alfa given as a bolus dose over
20-30 minutes followed by a two-hour (120 minute) infusion.
Patients receive a low or high dose depending on which Factor Xa
inhibitor they have received and the time they received the last
dose. Patients are evaluated for 30 days following andexanet alfa
administration. The co-primary efficacy endpoints are the maximum
percent reduction in anti-Factor Xa activity and assessment of
hemostasis over 12 hours following the infusion. Hemostatic
efficacy is assessed by an independent endpoint adjudication
committee as either excellent, good or poor/none.
Investor Event Webcast
InformationMembers of Portola’s senior management team,
together with Dr. C. Michael Gibson, ANNEXA-4 Executive Committee
member, Harvard Medical School professor and chairman of the
PERFUSE Study Group, will review these new interim results during a
conference call and live audio webcast today at 12:30 p.m. ET (9:30
a.m. PT) following the Late-Breaking Clinical Trial Session.
The conference call can be accessed by phone by calling (844)
452-6828 from the United States and Canada or 1
(765) 507-2588 internationally and using the passcode 8493604. To
access the live and subsequently archived webcast, go to the
Investor Relations section of the company's website at
http://investors.portola.com. A replay will be available for 30
days following the live event.
About 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’s first medicine Bevyxxa® (betrixaban), an oral,
once-daily Factor Xa inhibitor, was approved by the U.S. Food
and Drug Administration in June 2017. The company is also
working to advance two clinical programs for andexanet alfa, a
recombinant protein designed to reverse the anticoagulant effect in
patients treated with an oral or injectable Factor Xa inhibitor;
and cerdulatinib, a SYK/JAK inhibitor in development to treat
hematologic cancers. Portola's partnered program is focused on
developing selective SYK inhibitors for inflammatory conditions.
For more information, visit http://www.portola.com and
follow the Company on Twitter @Portola_Pharma.
Forward-Looking StatementsThis
announcement contains forward-looking statements, including
statements relating to Portola Pharmaceuticals’ expectations
regarding the regulatory status of betrixaban and andexanet alfa.
These statements are subject to significant risks and
uncertainties, and actual results could differ materially from
those projected. These risks and uncertainties include,
without limitation, risks and uncertainties related to the
regulatory process for betrixaban and andexanet alfa in the United
States and Europe. Risks and uncertainties relating to Portola
Pharmaceuticals and its business can be found in the “Risk Factors”
section of Portola Pharmaceuticals’ Annual Report on Form 10-K for
2017, which was filed with the SEC on March 1, 2018. Portola
Pharmaceuticals cautions investors not to place undue reliance
on the forward-looking statements contained in this release.
Portola Pharmaceuticals undertakes no duty or obligation to
update any forward-looking statements contained in this release as
a result of new information, future events or changes in Portola
Pharmaceuticals’ expectations.
Kcentra® is a registered trademark of CSL Behring GmbH.
Investor Contact:
Cara Miller
Portola PharmaceuticalsIR@portola.com
Media Contact: Laurie MasonsonPure
Communications lmasonson@purecommunications.com
Portola Pharmaceuticals (NASDAQ:PTLA)
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