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Portola Pharmaceuticals Announces Publication of Phase 3 APEX Study Design and Rationale in American Heart Journal
"Extended VTE prevention in acute medically ill patients is an important unmet medical need because studies have shown that well-identified patients are at high risk for life-threatening blood clots beginning at hospital admission and for several weeks after discharge. However, no anticoagulant therapy has been approved to protect patients during this period of risk. APEX is the only ongoing pivotal study evaluating one continuous therapy for hospital-to-home VTE prevention for these patients," said
The prospective, randomized, double-blind, multicenter, multinational APEX Study is evaluating the superiority of extended-duration anticoagulation with oral betrixaban (for up to 35 days in hospital and post-discharge) compared with standard of care anticoagulation with injectable enoxaparin (for 10 days) for VTE prevention in acute medically ill patients. The study will enroll close to 7,000 patients at more than 425 study sites worldwide. The primary efficacy endpoint is the composite of asymptomatic proximal deep venous thrombosis, symptomatic deep venous thrombosis, non-fatal pulmonary embolism or VTE-related death through day 35. The primary safety outcome is the occurrence of major bleeding.
"The APEX study is using biomarkers to identify and enroll patients at highest risk of blood clots who will most likely benefit from treatment with betrixaban, including those with elevated blood levels of D-dimer (a protein fragment present after a blood clot has developed) and those over age 75," said
About VTE Prevention in Acute Medically Ill Patients
Acute medically ill patients, who are at high risk for developing blood clots, are hospitalized due to a serious medical condition such as heart failure, stroke, infection, pulmonary disease or rheumatic disease. They are often elderly, frail, renally compromised and taking multiple concomitant medications. Acute medically ill patients represent the single largest category of patients at risk for thrombosis, with an estimated 30 million patients worldwide. Enoxaparin, the current standard of care, is limited to hospital use because it is administered by injection and is associated with an increase in major bleeding when administered in this population for extended use. The other novel oral Factor Xa inhibitors that have been studied in this population have also been associated with an increased rate of major bleeding. A well-identified population of medical patients is at risk for life-threatening blood clots during hospitalization and for several weeks after discharge, but currently no anticoagulant is approved to treat these patients for this extended time period.
Betrixaban is a small molecule anticoagulant that directly inhibits the activity of Factor Xa, an important validated target in the blood coagulation pathway, to prevent thrombosis. The compound has three properties that differentiate it from other oral anticoagulants: it has the longest half-life of all of the Factor Xa inhibitors for true once-daily dosing; it has a low level of clearance through the kidneys and has been studied in patients with severe renal impairment (excluding dialysis patients); and it is not metabolized by CYP3A4, a liver enzyme that metabolizes many drugs and can lead to drug-drug interactions. These properties are important for acute medically ill patients and may allow betrixaban to demonstrate efficacy in this population without the increase in major bleeding seen with other Factor Xa inhibitors.
Portola has full worldwide development and commercial rights to betrixaban.
Portola's wholly-owned, oral, once-daily Factor Xa inhibitor betrixaban is being evaluated in a biomarker-based Phase 3 study for "hospital to home" prophylaxis of venous thromboembolism (VTE) in acute medically ill patients. Betrixaban's properties may be particularly suited to potentially demonstrate efficacy without significantly increasing bleeding in this patient population. Currently, there is no anticoagulant approved for extended-duration VTE prophylaxis in acute medically ill patients.
Portola's second product candidate in the area of thrombosis, andexanet alfa, has the potential to be a first-in-class reversal agent to reverse the effects of Factor Xa inhibitors in patients who suffer a major bleeding episode or who require emergency surgery. Portola has entered into clinical collaboration agreements with all of the manufacturers of direct Factor Xa inhibitors, including
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 studied in patients with 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.
For more information, visit www.portola.com and follow the Company on Twitter @Portola_Pharma.
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: anticipated growth in the market for anticoagulants, clinical trial enrollment, cost, design and timing, and the potential efficacy, safety and activity of betrixaban, andexanet alfa and cerdulatinib. Risks that contribute to the uncertain nature of the forward-looking statements include: the accuracy of Portola's estimates regarding its ability to initiate and/or 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
*Cerdulatinib is a proposed International Nonproprietary Name (pINN).
iCohen AT, Harrington R, Goldhaber SZ, Hull R, Gibson CM, et al. The design and rationale for the Acute Medically Ill Venous Thromboembolism Prevention with Extended Duration Betrixaban (APEX) study. Am Heart J. 2014;167:335-41.