Portola Pharmaceuticals, Inc.® (Nasdaq:PTLA) today announced
results from three substudies of the pivotal Phase 3 APEX Study of
betrixaban, an oral, once-daily Factor Xa inhibitor anticoagulant
in development for the prevention of venous thromboembolism (VTE)
in acute medically ill patients. Findings from the analyses were
presented by the PERFUSE Study Group at the American Heart
Association (AHA) Scientific Sessions 2016.
In a retrospective APEX substudy on stroke, researchers assessed
the potential of extended-duration thromboprophylaxis with
betrixaban compared with standard-dose enoxaparin to reduce the
risk of stroke in hospitalized acute medically ill patients. The
substudy found that extended-duration betrixaban significantly
reduced all-cause stroke (0.54 percent for betrixaban vs. 0.97
percent for enoxaparin; RRR=44 percent) and ischemic stroke (0.48
percent for betrixaban vs. 0.91 percent for enoxaparin; RRR=47
percent) through 77 days of follow up. The results were presented
today by C. Michael Gibson, M.S., M.D., in the Sol Sherry
Distinguished Lecture in Thrombosis at AHA and simultaneously
published in the peer-reviewed journal Circulation.
“Stroke is a potentially fatal complication, but little is known
about the effectiveness of novel oral anticoagulants in preventing
stroke among the acute medically ill patient population. We were
encouraged to find that betrixaban was associated with a reduction
in the risk of all-cause stroke within 30 to 60 days, which was
driven predominantly by a reduction in ischemic stroke, without an
increased risk of major bleeding,” said Dr. Gibson, APEX Executive
Committee Member and Steering Committee Chairman; professor,
Harvard Medical School; and chairman of the PERFUSE Study Group.
“The unique properties of betrixaban may, in part, explain the
observed reduction in stroke without an increase in major bleeding
in this study population. These findings are especially important
because they demonstrate the potential for betrixaban to improve
stroke outcomes in these patients.”
A second retrospective APEX substudy, presented today at AHA by
Purva Jain, M.P.H., biostatistician for the PERFUSE Study Group,
found that both the first symptomatic VTE event and the total
number of symptomatic VTE events were reduced in patients treated
with extended-duration oral betrixaban compared with
standard-duration enoxaparin through the end of the study (abstract
#640). The results suggest that this reduction in the total burden
of symptomatic VTE events among patients taking betrixaban may
reduce the use of healthcare resources and alleviate costs related
to inpatient and outpatient care, and pharmacy use.
Lastly, in a poster session tomorrow, November 15, Gerald Chi,
M.D., of the PERFUSE Study Group, will present results from a third
retrospective APEX substudy. The findings showed that the addition
of a patient’s D-dimer level to the IMPROVE score (used to stratify
hospitalized medical patients by their risk for VTE) to derive the
IMPROVEDD score may further optimize VTE risk stratification.
Stroke Substudy (Abstract #277)In this
substudy, the mean age of study participants was 76 years, 45
percent were male, 13 percent had had a stroke, and 45 percent had
congestive heart failure. Stroke events were
adjudicated by an independent blinded-event adjudication committee
and assessed through last patient contact. The findings showed
that, among the 3,716 patients treated with extended-duration
betrixaban and the 3,716 patients treated with standard-of-care
enoxaparin:
- There were fewer all-cause strokes among those treated with
betrixaban than enoxaparin through 77 days of follow-up (0.54
percent vs. 0.97 percent; p=0.032).
- There were fewer ischemic strokes among those treated with
betrixaban than enoxaparin through 77 days of follow-up (0.48
percent vs. 0.91 percent; p=0.026).
- The composite endpoint of all-cause stroke and transient
ischemic attack (TIA) was also reduced among study subjects treated
with extended-duration betrixaban versus enoxaparin (0.65 percent
vs. 1.10 percent; p=0.034).
- Among patients at highest risk for stroke – i.e., those who had
a prior ischemic stroke or a history of congestive heart failure --
the risk of all-cause stroke was reduced with betrixaban compared
with enoxaparin (0.72 percent vs. 1.48 percent; p=0.019), as was
ischemic stroke (0.63 percent vs. 1.38 percent; p=0.014).
About the APEX StudyThe pivotal Phase 3 APEX
Study enrolled 7,513 patients at more than 450 clinical sites
worldwide and assessed the superiority of extended-duration
anticoagulation with oral betrixaban for 35-42 days compared with
standard-duration injectable enoxaparin for 10+4 days in preventing
VTE in high-risk acute medically ill patients. The primary efficacy
endpoint was a composite of asymptomatic proximal DVT (deep vein
thrombosis) (detected on ultrasound), symptomatic DVT (proximal or
distal), non-fatal pulmonary embolism (PE) and VTE-related death.
The primary safety endpoint was major bleeding through seven days
after drug discontinuation.
Results showed that betrixaban reduced the incidence of VTE
compared with enoxaparin at a p value approaching statistical
significance (p=0.054) in the primary efficacy analysis subgroup of
3,870 patients with elevated D-dimer levels. It also significantly
reduced VTE in several pre-specified analyses of the primary
efficacy analysis subgroup as well as in the overall study
population (p=0.006) of 7,513 patients. No statistical difference
in major bleeding was observed between the betrixaban and
enoxaparin arms in either of the primary analysis patient subgroup
or in the overall study population.
Full results from the multicenter, randomized, active-controlled
APEX Study were presented at the 62nd Annual International Society
on Thrombosis and Haemostasis (ISTH) Scientific and Standardization
Committee (SSC) Meeting in May 2016 and published online in The New
England Journal of Medicine in May 2016.i
About BetrixabanBetrixaban, an investigational
drug, 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.
Betrixaban has been given Fast Track designation by the U.S.
Food and Drug Administration (FDA). Portola submitted a New Drug
Application to the FDA in October 2016 seeking approval to market
betrixaban for extended-duration prophylaxis of VTE in acute
medically ill patients with risk factors for VTE. Portola expects a
response from the FDA within 60 days as to whether the NDA is
complete and acceptable for filing.
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
three programs, including betrixaban, an oral, once-daily Factor Xa
inhibitor; AndexXa™ (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 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, statements regarding development of our product
candidates, our regulatory applications and estimated timelines
associated therewith. Risks that contribute to the uncertain nature
of the forward-looking statements include: failure to obtain
regulatory approval for one or more of our product candidates, our
expectation that we will incur losses for the foreseeable future
and will need additional funds to finance our operations; the
results of our clinical trials related to the efficacy and safety
of our product candidates; our potential inability to manufacture
our product candidates on a commercial scale in a timely or
cost-efficient manner; the accuracy of our estimates regarding
expenses and capital requirements; regulatory developments in the
United States and foreign countries; 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, which was filed on November 7, 2016. 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.
i Cohen AT, Harrington RA, Goldhaber SZ, Hull RD, Wiens BL,
et al. Extended thromboprophylaxis with betrixaban in acutely ill
medical patients. N Engl J Med. 2016;375:534-544.
Investor Contact:
Ana Kapor
Portola Pharmaceuticals
ir@portola.com
Media Contact:
Julie Normart
W2O Group
jnormart@w2ogroup.com
415.946.1087
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