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Portola Pharmaceuticals Announces Topline Results from Phase 3 APEX Trial of Betrixaban for Prevention of Blood Clots in Acute Medically Ill Patients
—Full Data Set to be Presented at
—Company to Hold Conference Call Today at 8:30 am ET—
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
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
A summary of key topline efficacy and safety data follows:
|Primary Efficacy Analysis
|Primary Safety Analysis
|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
The APEX results will be presented at the
About VTE in Acute Medically Ill Patients
An 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 Details
To access the live conference call, please dial (844) 452-6828 from the U.S. and
Betrixaban 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.
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