Bristol-Myers Squibb (BMS), Pfizer, and Portola Pharmaceuticals said they will conduct a proof-of-concept study of PRT4445 and the investigational oral Factor Xa inhibitor Eliquis® (apixaban). PRT4445 is a universal antidote in clinical development designed to reverse the anticoagulant activity of any Factor Xa inhibitor.
The study—expected to start by year’s end—is designed to demonstrate the safety of PRT4445 and its ability to reverse the anticoagulation activity of Eliquis and other Factor Xa inhibitors, including betrixaban, Portola’s Phase III oral Factor Xa inhibitor. At present, no agents are approved to reverse the activity of Factor Xa inhibitors.
BMS and Pfizer said they will make an undisclosed cash payment to Portola upon initiation of the proof-of-concept study, as well as provide development and regulatory guidance. Portola retains full global development and commercialization rights for PRT4445.
PRT4445 is a modified human Factor Xa designed to sequester direct inhibitors such as apixaban, betrixaban, and rivaroxaban, thus allowing native Factor Xa to restore hemostasis. PRT4445 can also reduce the Xa inhibition properties of anti-thrombin dependent inhibitors.
Portola has presented nonclinical data on PRT4445 showing reductions in bleeding in animal models with enoxaparin, fondaparinux, and rivaroxaban. Additional in vivo and in vitro data have shown that PRT4445 can act as a universal antidote for direct Factor Xa inhibitors. PRT4445 and other antidotes that reverse the activity of Factor Xa inhibitors are designed for patients who, in rare instances, experience uncontrolled major bleeding or require emergency surgery.
Eliquis is the approved trade name for apixaban in Europe and the proposed trade name in the U.S. In May 2011, BMS and Pfizer won approval for Eliquis in the 27 countries of the European Union plus Iceland and Norway to prevent venous thromboembolic events in adult patients who have undergone elective hip or knee replacement surgery. BMS and Pfizer are also seeking approvals for Eliquis for stroke prevention in atrial fibrillation based on the Aristotle and Averroes studies.
On Sept. 21, BMS and Pfizer won a positive opinion for the drug from the Committee for Medicinal Products for Human Use of the European Medicines Agency for prevention of stroke and systemic embolism in adult patients with nonvalvular atrial fibrillation and with one or more risk factors for stroke.