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Portola's Factor Xa Inhibitor Betrixaban Successfully Passes Futility Analysis in Phase 3 APEX Study; Trial Continues as Planned and Remains on Track for Enrollment Completion by Year-End
The APEX Study is over 65 percent enrolled at over 450 sites worldwide. The Company expects to complete enrollment by the end of this year and report top-line results in early 2016.
"Given the positive outcome of the APEX futility analysis and the observation that the blinded aggregate VTE event rates in the study to date are on track, we are confident that we are enrolling patients who are at high risk of blood clots and who are most likely to benefit from betrixaban," said
About the APEX Study
The global, pivotal Phase 3 APEX Study is evaluating the superiority of extended-duration anticoagulation with oral betrixaban (for at least 35 days) compared with standard of care anticoagulation with injectable enoxaparin (for up to 14 days) for prevention of VTE in acute medically ill patients. The study is using a biomarker-based trial design to identify and enroll patients who are at highest risk of VTE and most likely to benefit from betrixaban – specifically those with an elevated level of D-dimer (a protein fragment present after a blood clot has developed) and those over age 75. The APEX Study is the only biomarker-based Phase 3 study for hospital-to-home prophylaxis of VTE in acute medically ill patients. It is also the only pivotal thrombosis trial evaluating a single anticoagulant for VTE prophylaxis in both the in-hospital and post-discharge settings. More than half of VTE events occur after hospital discharge in this patient population.i No anticoagulant is approved to treat these patients for this extended time period.
Betrixaban is an investigational small molecule anticoagulant that directly inhibits the activity of Factor Xa, an important validated target in the blood coagulation pathway, to prevent thrombosis. Betrixaban has distinct properties that may allow it to demonstrate clinical benefit without the significant imbalance in the risk of fatal bleeding seen with other agents in the class. These include a 19-25-hour half-life for true once-daily dosing; a low peak-to-trough drug concentration ratio that minimizes anticoagulant variability; the lowest renal clearance in the class; and no significant CYP3A4 metabolism, which may reduce the risk of drug-drug interactions. Betrixaban has been studied in patients with all degrees of renal function, including those with severe renal impairment (excluding dialysis patients).
Portola's wholly-owned, oral, once-daily Factor Xa inhibitor betrixaban is being evaluated in the only biomarker-based Phase 3 study for hospital-to-home prophylaxis of venous thromboembolism (VTE) in acute medically ill patients. Betrixaban's distinct properties may have the potential to allow the agent to demonstrate efficacy without the significant increase in the rate of major bleeding that was seen in this patient population with other Factor Xa inhibitors. If approved, betrixaban could be the first anticoagulant for both hospital and post-discharge VTE prophylaxis and the standard of care in this large market of more than 20 million patients in the G7 countries alone.
Andexanet alfa, a recombinant modified human Factor Xa molecule, has the potential to be a first-in-class antidote to reverse the effects of Factor Xa inhibitors in patients who suffer a major bleeding episode or who require emergency surgery. Andexanet alfa has been designated as a breakthrough therapy by the
Portola's product candidate in the area of hematologic cancer, cerdulatinib, is an orally available molecule that uniquely inhibits two validated tumor proliferation pathways – spleen tyrosine kinase (Syk) and janus kinase (JAK). It is currently being evaluated in a Phase 1/2a proof-of-concept study in patients with B cell leukemias or lymphomas with a focus on genetically-defined subtypes, as well as in patients who have failed therapy due to relapse or acquired mutations.
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: enrollment of a patient population in APEX that is at a high risk of blood clots and most likely to benefit from betrixaban; timing of completion of APEX enrollment and Portola's report of trial results; potential of betrixaban to demonstrate efficacy without the significant increase in bleeding; potential indications and market acceptance of betrixaban; potential for betrixaban to become standard of care; and Portola's intention of becoming a commercialized biopharmaceutical company with potentially groundbreaking products for thrombosis and hematologic cancers. Risks that contribute to the uncertain nature of the forward-looking statements include: the accuracy of Portola's estimates regarding its ability to complete its clinical trials; the success of Portola's clinical trials and the demonstrated efficacy of Portola's product candidates thereunder; the accuracy of Portola's estimates regarding its expenses and capital requirements; regulatory developments in
i Source: Amin et al. (2012). Duration of Venous Thromboembolism Risk Across a Continuum in Medically Ill Hospitalized Patients.