Portola, Bristol-Myers Squibb and Pfizer sign clinical collaboration agreement
Posted: 1 November 2012 | | No comments yet
Portola Pharmaceuticals, Inc., Bristol-Myers Squibb Company and Pfizer announced a clinical collaboration agreement…
Portola Pharmaceuticals, Inc., Bristol-Myers Squibb Company (NYSE: BMY) and Pfizer Inc. (NYSE: PFE) today announced a clinical collaboration agreement to conduct a proof-of-concept study of PRT4445 and the investigational oral Factor Xa inhibitor ELIQUIS® (apixaban). PRT4445 is a universal Factor Xa inhibitor antidote in clinical development designed to reverse the anticoagulant activity of any Factor Xa inhibitor. No agents are approved to reverse the activity of Factor Xa inhibitors.
The collaboration will be in effect during the clinical proof-of-concept study, which is anticipated to start by the end of this year. The study 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 3 oral Factor Xa inhibitor. Bristol-Myers Squibb and Pfizer will make an undisclosed cash payment to Portola upon initiation of the proof-of-concept study with ELIQUIS and will provide development and regulatory guidance for the study. Portola retains 100 percent global development and commercialization rights for PRT4445.
“Oral Factor Xa inhibitors address an important unmet need for patients requiring anticoagulant therapy, but as with all anticoagulants, there is a need for an antidote to help manage the concerns physicians have around infrequent but serious bleeding events.” said William Lis, chief executive officer of Portola. “This clinical collaboration brings together world-class expertise in the field of thrombosis from Bristol-Myers Squibb, Pfizer and Portola with the goal of accelerating the development of PRT4445 as an antidote to ELIQUIS, while allowing Portola to retain all rights to develop and commercialize the compound in the future.”
“Patient safety and improved patient outcomes have guided our clinical development program for ELIQUIS, including our efforts to identify a reversal agent for urgent clinical situations,” said Brian Daniels, senior vice president, Global Development and Medical Affairs, Bristol-Myers Squibb. “With our partner Pfizer, we look forward to working with Portola to advance the scientific understanding of the role of PRT4445 as a potential antidote for ELIQUIS.”
Major bleeding events occur infrequently in patients taking Factor Xa inhibitors (1-4% per year in clinical studies) and standard measures are employed to manage these events. Development of an agent specifically designed to reverse the activity of Factor Xa inhibitors may provide an antidote for patients who, in rare instances, experience an uncontrolled major bleeding event or require emergency surgery.
PRT4445 is a novel recombinant protein being developed to address serious, uncontrolled bleeding by reversing the anticoagulant activity of Factor Xa inhibitors and low molecular weight heparins in Factor Xa inhibitor-treated patients experiencing uncontrolled major bleeding or requiring emergency surgery. PRT4445 is a modified version of human Factor Xa designed to sequester direct inhibitors (apixaban, betrixaban, rivaroxaban), thereby allowing native Factor Xa to restore hemostasis. In addition, PRT4445 can reduce the Xa inhibition properties of anti-thrombin dependent inhibitors.
Portola has presented nonclinical data on PRT4445 at multiple major scientific conferences and has shown reductions in bleeding in animal models with enoxaparin, fondaparinux and rivaroxaban. Additional in vivo and in vitro data have shown that PRT4445 has the potential to act as a universal antidote for the class of direct Factor Xa inhibitors.
ELIQUIS is the approved trade name for apixaban in Europe and the proposed trade name in the U.S. ELIQUIS is not approved for the prevention of stroke or systemic embolism in patients with atrial fibrillation in any country. In May 2011, Bristol-Myers Squibb and Pfizer announced the first regulatory approval for ELIQUIS in the 27 countries of the European Union plus Iceland and Norway for the prevention of venous thromboembolic events (VTE) in adult patients who have undergone elective hip or knee replacement surgery.
Bristol-Myers Squibb and Pfizer continue to progress the ELIQUIS application for stroke prevention in atrial fibrillation based on the ARISTOTLE and AVERROES studies. On September 21, 2012, Bristol-Myers Squibb and Pfizer Inc. announced that the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) adopted a positive opinion recommending that ELIQUIS be granted approval for the prevention of stroke and systemic embolism in adult patients with nonvalvular atrial fibrillation and with one or more risk factors for stroke. On September 26, 2012, The U.S. Food and Drug Administration (FDA) acknowledged receipt of the ELIQUIS (apixaban) New Drug Application (NDA) resubmission to reduce the risk of stroke and systemic embolism in adult patients with nonvalvular atrial fibrillation. The FDA has deemed the resubmission a complete response to its June 22, 2012 Complete Response Letter (CRL) that requested additional information on data management and verification from the ARISTOTLE trial. The FDA Prescription Drug User Fee Act (PDUFA) date is March 17, 2013.
ELIQUIS is also being investigated in Phase 3 trials for the treatment of VTE.