Portola Pharmaceuticals Announces Topline Results from Phase 3 APEX Trial of Betrixaban for Prevention of Blood Clots in Acut...
24 Mars 2016 - 12:00PM
—Full Data Set to be Presented at International
Society of Thrombosis and Haemostasis (ISTH) Congress in
May—
Portola Pharmaceuticals (Nasdaq:PTLA) today announced topline data
from the Phase 3 APEX (Acute Medically Ill VTE Prevention with
Extended Duration Betrixaban) Study, which evaluated the
superiority of extended-duration anticoagulation with oral
betrixaban compared with standard of care anticoagulation with
injectable enoxaparin for the prevention of venous thromboembolism
(VTE), or blood clots, in acute medically ill patients. These are
patients who are hospitalized for serious common medical
conditions, such as heart failure, stroke, infection and pulmonary
disease.
APEX was designed to assess the relative risk (RR) in the
composite endpoint of ultrasound-detected (asymptomatic) proximal
deep venous thrombosis (DVT), symptomatic DVT, non-fatal pulmonary
embolism (PE) or VTE-related death in high-risk acute medically ill
patients treated with oral betrixaban for 35-47 days versus
standard of care preventive anticoagulation with injectable
enoxaparin dosed for 10±4 days. APEX enrolled 7,513 patients at
more than 450 clinical sites worldwide.
The primary efficacy and safety analysis consisted of three
pre-specified patient groups of increasing sample size: Cohort 1 -
patients with elevated D-dimer levels (62 percent of the overall
study population), Cohort 2 - patients with elevated D-dimer levels
or age ≥75 years (91 percent of the overall study population), and
the overall study population. By protocol definition, primary
efficacy analysis testing of Cohort 1 was done first and required a
p value of 0.05 or less in order to test Cohort 2, which in turn
required a p value of 0.05 or less in order to test the overall
study population.
Cohort 1 achieved a p value of 0.054, which did not meet the
threshold. Cohort 2 and the overall study population achieved p
values of 0.029 and 0.006, respectively. There was no statistical
difference in major bleeding between the betrixaban and enoxaparin
arms in any of these three patient groups. The number of fatal
bleeds was balanced between the two arms, and the number of
intracranial hemorrhages was numerically lower in the betrixaban
arm. Positive net clinical benefit with betrixaban was
observed.
“While we understand that the interpretation of these
statistical and clinical results will be subject to discussions
with regulatory agencies, we and the APEX Study academic leadership
believe that the data in Cohort 1 were sufficiently strong to
support a full assessment of Cohort 2 and the overall study
population,” said Bill Lis, chief executive officer of Portola. “We
believe the overall robustness of the efficacy and safety results
in this high-risk patient population, including the positive net
clinical benefit observed, provide ample evidence to support the
submission of an NDA later this year.”
APEX is a groundbreaking study because it is the first
thrombosis prevention trial to incorporate an enrichment strategy
and statistical analysis plan derived from the U.S. Food and Drug
Administration (FDA) guidance document on enrichment strategies for
clinical trials. This approach was incorporated into the APEX
design in cooperation with the FDA and European Medicines Agency
(EMA).
A summary of key topline efficacy and safety data follows:
|
Primary Efficacy Analysis (VTE) |
|
Primary Safety Analysis (Major
Bleeding) |
|
RR* |
p value |
|
RR* |
p value |
Cohort 1: Elevated D-Dimer |
0.806 |
0.054 |
|
0.88 |
0.722 |
Cohort 2: Elevated D-Dimer or Age >75 |
0.800 |
0.029 |
|
1.19 |
0.564 |
Overall Study Population |
0.760 |
0.006 |
|
1.19 |
0.554 |
*RR = relative risk calculated as the frequency of events with
betrixaban divided by the frequency of events with
enoxaparin
"VTE is a common disorder that contributes significantly to the
burden of morbidity and mortality,” said Alexander (Ander) T.
Cohen, MBBS, M.Sc., M.D., co-principal investigator of APEX and
honorary consultant vascular physician at King’s College London.
“The attributable risk of acute medical illnesses to VTE is at
least 25% and a reduction of this risk will result in important
health benefits. APEX is the first study of extended
thromboprophylaxis with a Factor Xa inhibitor in the large
population of acute medically ill patients to reduce VTE without an
increase in major bleeding. Based on the results of the APEX trial,
betrixaban could have an important role to play in preventing VTE
in this setting."
The APEX results will be presented at the International Society
on Thrombosis and Haemostasis (ISTH) Congress on Friday, May 27,
2016. Full data will also be submitted for publication.
About VTE in Acute Medically Ill PatientsAn
estimated 20 million acute medically ill patients in the G7
countries are at risk of developing VTE either while in the
hospital or following discharge. More than 1 million VTEs and
150,000 VTE-related deaths occur in acute medically ill patients
each year in the G7 countries, despite the use of injectable
enoxaparin in the hospital. Although more than half of VTE events
occur after the patient is discharged from the hospital, no
anticoagulant, including any of the marketed oral Factor Xa
inhibitors, is approved for VTE prophylaxis in both the hospital
setting and for the extended post-discharge period.
Conference Call DetailsTo access the live
conference call, please dial (844) 452-6828 from the U.S. and
Canada or +1 (765) 507-2588 internationally, and use the passcode
79012351. Please dial in 10 minutes prior to the start of the call.
To access the live and subsequently archived webcast of the
conference call, go to the Investor Relations section of the
company’s website at http://investors.portola.com. Please connect
to the website at least 15 minutes prior to the call to allow for
any software download that may be necessary. A replay of the
webcast will be available on the Company’s website for 14 days
following the live event.
About BetrixabanBetrixaban directly inhibits
the activity of Factor Xa, an important validated target in the
blood coagulation pathway, to prevent life-threatening thrombosis.
Betrixaban has distinct properties that may allow it to demonstrate
clinical benefit without the significant imbalance in the risk of
major bleeding seen with other agents in the class. These include a
19-25-hour half-life for once-daily dosing; a low peak-to-trough
drug concentration ratio that minimizes anticoagulant variability;
low renal clearance; and no significant CYP3A4 metabolism, which
may reduce the risk of drug-drug interactions.
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 is advancing
its three programs using novel biomarker and genetic approaches
that may increase the likelihood of clinical, regulatory and
commercial success of its potentially life-saving therapies. These
programs include betrixaban, an oral, once-daily Factor Xa
inhibitor; 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
www.portola.com and follow the Company on Twitter
@Portola_Pharma.
Forward-looking Statement 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 the potential for study results to
support an application for regulatory approval of betrixaban, the
potential for betrixaban, subject to regulatory approval, to play a
role in both in-hospital and post-discharge prevention of VTE; our
interpretation and characterization of APEX study results. Risks
that contribute to the uncertain nature of the forward-looking
statements include: results of discussions with regulatory
authorities regarding interpretation of full APEX study results in
light of cohort 1 falling short of its primary efficacy threshold;
that FDA and other regulatory authorities may not approve
betrixaban; whether the clinical results of betrixaban will meet
the regulatory requirements for approval; whether regulatory
submissions will occur or will be submitted in a timely manner,
that marketing approvals may not be granted, or if granted, may
have significant limitations on their use or require additional
studies; the accuracy of Portola's estimates regarding its expenses
and capital requirements; regulatory developments in the United
States and foreign countries; Portola's ability to obtain and
maintain intellectual property protection for its product
candidates; and the loss of 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, including its Annual Report on Form 10-K, which was
filed on February 29, 2016. 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.
Investor Contact:Ana KaporPortola
Pharmaceuticalsir@portola.com
Media Contact:Julie NormartW2O
Groupjnormart@w2ogroup.com
Portola Pharmaceuticals (NASDAQ:PTLA)
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