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|Portola Announces Positive Phase 2 Study Results Showing Factor Xa Inhibitor Antidote PRT4445 Reverses Anticoagulant Activity of Eliquis(R)|
"Clinicians are gaining expertise with the use of Factor Xa inhibitors, but there is no effective way to reverse or stop the anticoagulation effect of these agents when a patient requires it," said Dr. Crowther. "These are the first Phase 2 data to indicate that a product can reverse the anticoagulation effect of a Factor Xa inhibitor."
Major bleeding events occur infrequently in patients taking Factor Xa inhibitors (1-4 percent per year in several clinical studies involving patients taking a Factor Xa inhibitor on a chronic basis), and standard measures are currently employed to manage these events. However, there is presently no approved antidote or reversal agent that is specifically intended for use against Factor Xa inhibitors. Development of andexanet alfa, specifically designed to reverse the activity of Factor Xa inhibitors, may provide an antidote for patients who experience an uncontrolled major bleeding event or require emergency surgery.
Portola entered into a collaboration agreement with
"The lack of an effective antidote is restricting the use of Factor Xa inhibitors to patients at low risk for bleeding or requiring surgery. Leading clinicians have identified an antidote as a significant unmet clinical need," said
Phase 2 Study Design and Results
Results demonstrated a dose-dependent reversal of the anticoagulant activity of Eliquis. Two minutes after administration of 420 mg andexanet alfa (n=6), the anticoagulant activity of Eliquis decreased by greater than 95 percent as measured by anti-Factor Xa activity. Similarly, the 210 mg dose reduced anti-Factor Xa activity by 80 percent compared with saline (n=9). The reversal of anti-Factor Xa activity correlated with a reduction in the level of free, unbound Eliquis in the plasma consistent with the mechanism of action of andexanet alfa.
Safety data for all 27 healthy volunteers after 48 days of follow-up showed no thrombotic events, serious adverse events or premature discontinuations of andexanet alfa. The incidence of adverse events with andexanet alfa was similar to that with the control. No antibodies were generated against andexanet alfa, endogenous Factor Xa or Factor X.
About Andexanet Alfa
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 require emergency surgery. Portola has entered into collaboration agreements with
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. Portola plans to file an Investigational New Drug (IND) application in the third quarter of 2013and 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
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