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Portola Pharmaceuticals Announces Positive Phase 2 Data With FDA-Designated Breakthrough Therapy Andexanet Alfa and Enoxaparin
--Data Extend the Potential for Andexanet as an Antidote Beyond
Oral Factor Xa Inhibitors to Injectible Low Molecular Weight Heparin--
"These Phase 2 data with enoxaparin are the first to demonstrate that andexanet alfa, in addition to reversing the anticoagulation activity of oral Factor Xa inhibitors, can reverse a low molecular weight heparin, thereby expanding the potential use of andexanet to enoxaparin-treated patients. There is an established threshold at which the anticoagulation activity of enoxaparin is considered clinically reversed, and andexanet hit this target," said
In the randomized, double-blind, placebo-controlled, dose-escalation, Phase 2 proof-of-concept study, 27 healthy volunteers were administered enoxaparin 40 mg subcutaneously once daily for six days and then randomized in a 2:1 ratio to andexanet alfa administered as an IV bolus (210 mg or 420 mg) or to placebo. Enoxaparin is an indirect inhibitor of Factor Xa, and results showed that anti-Factor Xa activity was reduced within two minutes to a level below the established enoxaparin therapeutic anticoagulation threshold. Inhibition of thrombin generation was also restored to normal baseline levels immediately following completion of the bolus dose. The reversal of anti-Factor Xa activity was maintained for two to three hours after the single bolus administration as was the normalization of thrombin generation. Andexanet alfa was well tolerated with no thrombotic events or serious adverse events reported. No antibodies to andexanet alfa, Factor Xa or Factor X were observed.
The andexanet alfa abstract is now publically available at www.isth.org. Details of the presentations follow.
Abstract Title: Reversal of Enoxaparin-Induced Anticoagulation in Healthy Subjects by Andexanet Alfa (PRT064445), an Antidote for Direct and Indirect FXA Inhibitors -- A Phase 2 Randomized, Double-Blind, Placebo-Controlled Trial (abstract #COA01)
Poster Presentation Date, Time and Location:
Oral Presentation Date, Time and Location:
About the Need for a Factor Xa Inhibitor Reversal Agent
Currently, millions of patients are treated with Factor Xa inhibitors for short-term use or chronic conditions, and the anticoagulant market is expected to continue to grow. Recent patient datai confirm earlier clinical trial results showing that, annually, between 1-4 percent of patients treated with Factor Xa inhibitors may experience major bleeding and an additional 1 percent may require emergency surgery. Development of a specific antidote designed to reverse the anticoagulant activity of Factor Xa inhibitors may provide an important treatment option for patients who experience a major bleeding event or require emergency surgery.
About Andexanet Alfa
Andexanet alfa, an
About the Andexanet Alfa Clinical Development Program
Portola is evaluating andexanet alfa in Phase 3 studies with
Results from three separate Phase 2 proof-of concept studies with Eliquis, XARELTO® and enoxaparin in healthy volunteers demonstrated that andexanet alfa immediately reversed the anticoagulation activity of each Factor Xa inhibitor and that the reversal could be sustained. Andexanet alfa has been shown to be well tolerated in clinical studies, which have included more than 100 healthy volunteers, with no thrombotic events or antibodies to Factor Xa or Factor X observed.
A Phase 2 proof-of-concept study with
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 worldwide.
Portola's second product candidate in the area of thrombosis, andexanet alfa, 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 1/2 proof-of-concept study 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: Portola's plans for future clinical studies and pursuit of an Accelerated Approval process for andexanet alfa, anticipated growth in the market for anticoagulants, clinical trial cost, design and timing, and the potential efficacy, safety and activity of andexanet alfa. 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; our ability to manufacture andexanet alfa; regulatory developments in
*Cerdulatinib is a proposed International Nonproprietary Name (pINN).
i Source: Truven MARKETSCAN® Commercial, Medicare Supplemental and Medicaid Database (12 months ending