Portola Pharmaceuticals, Inc. Receives FDA Orphan Drug Designation For Andexanet Alfa, Its Breakthrough-Designated Factor Xa Inhibitor Antidote
SOUTH SAN FRANCISCO, Calif., Feb. 26, 2015 (GLOBE NEWSWIRE) -- Portola Pharmaceuticals (Nasdaq:PTLA) today announced that andexanet alfa, a U.S. Food and Drug Administration (FDA)-designated breakthrough therapy, has been granted orphan drug designation by the FDA's Office of Orphan Products Development for reversing the anticoagulant effect of direct or indirect Factor Xa inhibitors in patients experiencing a serious uncontrolled bleeding event or who require urgent or emergent surgery. Currently, there is no approved antidote for these patients.
Andexanet alfa has the potential to become the first approved universal antidote for Factor Xa inhibitors and the standard of care to manage bleeding associated with these anticoagulants.
"Orphan drug designation for andexanet alfa recognizes its potential to address a significant unmet medical need and to advance the field by helping patients who currently have no treatment options. Four factor prothrombin complex concentrates (PCCs), which are indicated for warfarin reversal, have not demonstrated reversal of Factor Xa inhibitor activity and have a black box warning for fatal and non-fatal thromboembolic events," said Bill Lis, chief executive officer of Portola. "This designation also provides significant business value to Portola, including market exclusivity, tax credits and a waiver of FDA marketing application fees."
The FDA's Orphan Drug Designation program provides orphan status to drugs and biologics that are defined as those intended for the safe and effective treatment, diagnosis or prevention of rare diseases/disorders that currently affect fewer than 200,000 people in the United States.i
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 dataii 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. Annually, more than 100,000 U.S. patients are currently impacted and may benefit from an antidote. With the expected increase in adoption of these anticoagulants, Portola projects that this number will increase by the year 2020 to up to 200,000 patients in the United States and an estimated 500,000 patients in the G7 countries. Development of a specific antidote designed to reverse the anticoagulant activity of Factor Xa inhibitors may provide an important treatment option for these patients.
About Andexanet Alfa
Andexanet alfa is a modified human Factor Xa molecule that acts as a decoy to target and sequester with high specificity both oral and injectable Factor Xa inhibitors in the blood. Once bound, the Factor Xa inhibitors are unable to bind to and inhibit native Factor Xa, thus allowing for the restoration of normal hemostatic processes. Andexanet alfa has the potential to address numerous clinical scenarios where an antidote is needed by allowing for flexible and controlled reversal. This can be short-acting through the administration of an IV bolus or longer-acting with the addition of an extended infusion.
Andexanet alfa is the only compound being studied as a reversal agent for Factor Xa inhibitors that directly and specifically corrects anti-Factor Xa activity -- the anticoagulant mechanism of these agents.
About the Andexanet Alfa Clinical Development Program
Portola is evaluating andexanet alfa in two randomized, placebo-controlled Phase 3 ANNEXA™ (Andexanet Alfa a Novel Antidote to the Anticoagulant Effects of fXA Inhibitors) registration studies using pharmacodynamic endpoints agreed to with the FDA, including anti-Factor Xa inhibitor units, to demonstrate efficacy. The Company reported statistically significant results from the first part of the Phase 3 ANNEXA-A study, which evaluated andexanet alfa administered as a single IV bolus dose with Bristol-Myers Squibb Company and Pfizer Inc.'s direct Factor Xa inhibitor apixaban, and from the first part of the Phase 3 ANNEXA-R study with Bayer HealthCare and Janssen's direct Factor Xa inhibitor rivaroxaban. The second parts of the ANNEXA-A and ANNEXA-R studies are ongoing and are evaluating a bolus plus a continuous infusion of andexanet alfa to sustain the reversal of anticoagulation activity.
ANNEXA-4, a Phase 4 single-arm confirmatory study in patients receiving apixaban, rivaroxaban, edoxaban or enoxaparin (a low molecular weight heparin and indirect Factor Xa inhibitor) who present with an acute major bleed is also ongoing. Data from the ANNEXA-A and ANNEXA-R studies, as well as data from a small number of patients from ANNEXA-4, will serve as the clinical basis of a Biologics License Application (BLA), which Portola plans to submit under an Accelerated Approval pathway.
Results from four separate Phase 2 proof-of concept studies with apixaban, rivaroxaban, edoxaban 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 140 healthy volunteers. No thrombotic events or antibodies to Factor Xa or Factor X have been observed.
A Phase 2 proof-of-concept study with Portola's investigational Factor Xa inhibitor betrixaban is planned.
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 its three wholly-owned programs using novel biomarker and genetic approaches that may increase the likelihood of clinical, regulatory and commercial success of its potentially life-saving therapies. Portola's partnered program is focused on developing selective Syk inhibitors for inflammatory conditions.
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 U.S. Food and Drug Administration (FDA)-designated breakthrough therapy, is a recombinant protein designed to reverse the anticoagulant activity in patients treated with an oral or injectable Factor Xa inhibitor. Andexanet alfa has the potential to be a first-in-class antidote for anticoagulated patients who suffer a major bleeding episode or require emergency surgery. Portola has entered into Phase 3 clinical collaboration agreements with all of the manufacturers of direct Factor Xa inhibitors – Bristol-Myers Squibb and Pfizer (Eliquis [apixaban]), Bayer HealthCare and Janssen Pharmaceuticals (XARELTO® [rivaroxaban]), and Daiichi Sankyo (edoxaban) – while retaining all commercial rights to andexanet alfa. The Company is currently evaluating andexanet alfa in the Phase 3 and Phase 4 ANNEXA™ (Andexanet Alfa a Novel Antidote to the Anticoagulant Effects of fXA Inhibitors) registration studies.
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: Portola's plans for future clinical studies and pursuit of an accelerated approval process for andexanet alfa, timing of the submission of our BLA for andexanet alfa, anticipated benefits of an orphan drug designation, anticipated growth in the market for anticoagulants, the potential market, indications, efficacy, safety and activity of andexanet alfa, and the potential market and indications for Portola's other product candidates. 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; Portola's ability to manufacture andexanet alfa; regulatory developments in the United States and foreign countries; Portola's ability to obtain and maintain intellectual property protection for its product candidates; and the loss of key scientific or management personnel. These and other risks and uncertainties are described more fully in Portola's most recent filings with the Securities and Exchange Commission, including its Annual Report on Form 10-K and most recent Quarterly Report on Form 10-Q. All forward-looking statements contained in this press release speak only as of the date on which they were made. Portola undertakes no obligation to update such statements to reflect events that occur or circumstances that exist after the date on which they were made.
i http://www.fda.gov/ForIndustry/DevelopingProductsforRareDiseasesConditions/ucm2005525.htm. Accessed February 24, 2015.
ii Source: Truven MARKETSCAN® Commercial, Medicare Supplemental and Medicaid Database (12 months ending September 2013).CONTACT: Media: Joey Fleury, BrewLife, firstname.lastname@example.org, 415.946.1090 Investors: Alexandra Santos, Portola Pharmaceuticals, email@example.com, 650.246.7239
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