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Portola to Initiate Phase 2 Study Evaluating the Safety and Effectiveness of Its Factor Xa Inhibitor Antidote PRT4445 in Reversing the Anticoagulant Activity of Investigational Factor Xa Inhibitor Edoxaban

Portola Pharmaceuticals, Inc. (NASDAQ: PTLA) today announced that it has entered into a clinical collaboration agreement with Daiichi Sankyo Company, Limited to conduct a Phase 2 study evaluating the safety and effectiveness of its investigational Factor Xa inhibitor antidote PRT4445 at several different doses to reverse the anticoagulant effects of Daiichi Sankyo's investigational oral, once-daily, direct Factor Xa inhibitor edoxaban in healthy volunteers. PRT4445 has a tentatively approved International Nonproprietary Name (INN) of andexanet alfa.

Andexanet alfa is a recombinant protein designed to reverse the anticoagulant activity in patients treated with a Factor Xa inhibitor who suffer an uncontrolled bleeding episode or undergo emergency surgery. Edoxaban is an investigational anticoagulant that specifically and reversibly inhibits Factor Xa, an important factor in the coagulation system that leads to blood clotting.

The collaboration will be in effect throughout the Phase 2 study, for which Daiichi Sankyo will provide development and regulatory guidance. Portola retains all global development and commercialization rights for andexanet alfa. Daiichi will make an undisclosed cash payment to Portola upon initiation of the edoxaban study.

Clinical trial results suggest that patients treated with novel oral anticoagulants may experience uncontrolled bleeding (annually between 1 and 4 percent) and some may require emergency surgery. The lack of an effective reversal agent, or antidote, for patients on Factor Xa inhibitors is an unmet need as currently there is no such agent approved for use against Factor Xa inhibitors.

About Andexanet Alfa Andexanet alfa is a novel recombinant protein designed to reverse the anticoagulant activity in patients treated with a Factor Xa inhibitor who suffer an uncontrolled bleeding episode or need to undergo emergency surgery. Andexanet alfa is similar to native Factor Xa, but has been modified to restrict its biological activity to the reversal of the anticoagulant effects of Factor Xa inhibitors. Andexanet alfa acts as a Factor Xa decoy that binds and sequestors direct Factor Xa inhibitors in the blood. Once bound to andexanet alfa, the Factor Xa inhibitors are unable to bind to and inhibit native Factor Xa. The native Factor Xa is then available to participate in the coagulation process and restore hemostasis.

Results from a Phase 1 single ascending dose safety and tolerability study of andexanet alfa conducted by Portola in 32 healthy volunteers in the United States showed no apparent safety signals, including no thrombotic adverse events.

About Portola Pharmaceuticals, Inc. Portola is a biopharmaceutical company focused on the development and commercialization of novel therapeutics in the areas of thrombosis (blood clots), other hematologic disorders and inflammation for patients who currently have limited or no approved treatment options. Portola's current development-stage portfolio consists of three compounds discovered through its internal research efforts and one discovered by Portola scientists during their time at a prior company. Portola's two lead programs address significant unmet medical needs in the area of thrombosis.

Portola's lead compound, betrixaban, is an investigational, novel, oral, once-daily inhibitor of Factor Xa in Phase 3 development for extended duration prophylaxis (preventive treatment) of a form of thrombosis known as venous thromboembolism (VTE) in acute medically ill patients. Currently, there is no anticoagulant approved for extended duration VTE prophylaxis in this population.

Portola's second lead development candidate, andexanet alfa, is a recombinant protein designed to reverse the anticoagulant activity in patients treated with a Factor Xa inhibitor who suffer an uncontrolled bleeding episode or need to undergo emergency surgery. Portola has entered into collaboration agreements with Bristol-Myers Squibb Company and Pfizer Inc., with Bayer Pharma AG and Janssen Pharmaceuticals, Inc., and with Daiichi Sankyo to study andexanet alfa with Eliquis® (apixaban), XARELTO® (rivaroxaban) and edoxaban, respectively, in Portola's Phase 2 studies. Portola retains full, worldwide commercial rights with respect to andexanet alfa.

Portola's third product candidate, PRT2070, is an orally available kinase inhibitor being developed for hematologic (blood) cancers and inflammatory disorders. PRT2070 inhibits spleen tyrosine kinase (Syk) and janus kinases (JAK), enzymes that regulate important signaling pathways. Subject to regulatory approval, Portola plans to initiate a Phase 1/2 clinical study of PRT2070 in 2013 in patients with B-cell hematologic cancers who have failed or relapsed on existing marketed therapies or products in development, including patients with identified mutations. Portola's fourth program, PRT2607 and other highly selective Syk inhibitors, is partnered with Biogen Idec Inc.

Forward-looking statement 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 use of betrixaban as a Factor Xa inhibitor, the use of PRT4445, which has a tentatively approved International Nonproprietary Name (INN) of andexanet alfa, to reverse the anticoagulant activity in patients treated with a Factor Xa inhibitor, the use of PRT2070 or PRT2607 as kinase inhibitors and any of Portola's clinical trials, including Portola's Phase 3 APEX study for betrixaban, Phase 2 proof-of-concept studies for PRT4445 and Phase1/2 study for PRT2070. 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 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 filings with the Securities and Exchange Commission, including without limitation its Registration Statement on Form S-1 that was originally filed with the Securities and Exchange Commission on April 12, 2013, and the amendments thereto. 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.

Posted-In: News FDA

 

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