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Portola Announces PRT4445 Produces Rapid, Sustained and Dose-Related Reversal of Anticoagulant Activity of Eliquis® in Phase 2 Study
Results Are From First in Series of Phase 2 Proof-of-Concept Studies
SOUTH SAN FRANCISCO, Calif. (May 8, 2013) – Portola Pharmaceuticals, Inc. today announced efficacy and safety data from the Phase 2 proof-of-concept study of PRT4445 in healthy volunteers who were administered the Factor Xa inhibitor Eliquis® (apixaban). Analysis of anticoagulation markers and plasma concentration levels of Eliquis in blood samples taken from the subjects indicates that PRT4445 produces a rapid, sustained and dose-related reversal of the anticoagulant activity of Eliquis. In addition, no serious adverse events were reported. Additional details will be presented at an upcoming medical conference.
PRT4445 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.
In October 2012, Portola entered into a three-way agreement with Bristol-Myers Squibb and Pfizer for the Phase 2 study with Eliquis, which is the first in a series of Phase 2 proof-of-concept studies that are evaluating the safety and activity of PRT4445 in healthy volunteers who have been administered one of several Factor Xa inhibitors. Portola is conducting a separate Phase 2 study with PRT4445 and the Factor Xa inhibitor XARELTO® (rivaroxaban) and expects to complete it in 2013.
Need for Reversal Agent for Factor Xa InhibitorsClinical trial results suggest that, depending on their underlying medical condition, annually between 1 and 4 percent of patients treated with Factor Xa inhibitors for short-term use or chronic conditions will experience uncontrolled bleeding and an additional 1 percent will require emergency surgery. Currently, there is no antidote or reversal agent approved for use against Factor Xa inhibitors. Leading clinicians have identified, and the United States Food and Drug Administration (FDA) has recognized, the lack of an effective reversal agent for Factor Xa inhibitors as a significant unmet clinical need.
About PRT4445PRT4445 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 undergo emergency surgery. PRT4445 is structurally very similar to native Factor Xa, but it has a number of limited modifications intended to restrict its biological activity to reverse the effects
of Factor Xa inhibitors. PRT4445 acts as a Factor Xa decoy that binds to Factor Xa inhibitors in the blood. Once bound to PRT4445, the inhibitors are unable to bind to and inhibit native Factor Xa. The native Factor Xa then becomes available to participate in the coagulation process and restore hemostasis (normal clotting).
Results of a Phase 1 single ascending dose safety and tolerability study, conducted by Portola in 32 healthy volunteers in the United States, showed that PRT4445 was generally well tolerated with no apparent safety signals.
About Portola Pharmaceuticals, Inc.
Portola is a biopharmaceutical company focused on the development and commercialization of novel therapeutics in the areas of thrombosis, 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, or blood clots. Portola’s lead compound, betrixaban, is a novel oral once-daily inhibitor of Factor Xa in Phase 3 development for extended duration prophylaxis, or preventive treatment, of a form of thrombosis known as venous thromboembolism, or 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, PRT4445, 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. Portola has entered into a collaboration agreement with Bristol-Myers Squibb Company and Pfizer Inc. and a collaboration agreement with Bayer Pharma AG and Janssen Pharmaceuticals, Inc. to study PRT4445 with Eliquis® and XARELTO®, respectively, in Portola’s Phase 2 studies. Portola retains full, worldwide commercial rights with respect to PRT4445.
Portola’s third product candidate, PRT2070, is an orally available kinase inhibitor being developed for hematologic, or blood, cancers and inflammatory disorders. PRT2070 inhibits spleen tyrosine kinase, or Syk, and janus kinases, or 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.