Date: 2014-07-07
Type of information: Clinical research agreement
Compound: andexanet alfa (modified Factor Xa)
Company: Portola Pharmaceuticals (USA - CA) Daiichi Sankyo (Japan)
Therapeutic area: Cardiovascular diseases - Hematologic diseases
Type agreement: clinical research
Action mechanism: Andexanet alfa is a first-in-class recombinant, modified Factor Xa molecule. It is being developed as a direct reversal agent for patients receiving a Factor Xa inhibitor who suffer a major bleeding episode or who may require emergency surgery. Andexanet alfa acts as a Factor Xa decoy that targets and sequesters with high specificity both direct and indirect Factor Xa inhibitors in the blood. Once bound, the Factor Xa inhibitors are unable to bind to and inhibit native Factor Xa, thus allowing for the restoration of normal hemostatic processes. Andexanet alfa has the potential to address numerous clinical scenarios by allowing for flexible and controlled reversal, which can be short-acting through the administration of an IV bolus or longer-acting with the addition of an extended infusion.
Disease:
Details: * On July 7, 2014, Portola Pharmaceuticals announced that it has entered into a second clinical collaboration agreement with Daiichi Sankyo to study andexanet alfa, Portola\'s investigational Factor Xa inhibitor antidote, in Phase 3 registration studies with Daiichi Sankyo\'s Factor Xa inhibitor edoxaban. Portola\'s original collaboration agreement with Daiichi Sankyo, announced in June 2013, covered the conduct of a Phase 2 proof-of-concept study, for which results are anticipated later this year. The Phase 3 edoxaban studies, known as ANNEXA™- E (Andexanet Alfa a Novel Antidote to the Anticoagulant Effects of fXA Inhibitors - Edoxaban), are expected to start in 2015.
Portola is evaluating andexanet alfa in Phase 3 studies with BMS and Pfizer Inc.\'s Eliquis® (apixaban) and Bayer HealthCare and Janssen\'s Xarelto® (rivaroxaban). These randomized, double-blind, placebo-controlled studies are designed to evaluate the safety and efficacy of andexanet alfa in reversing Eliquis- or Xarelto®-induced anticoagulation rapidly after an IV bolus and sustaining that effect through a continuous infusion. Results from three separate Phase 2 proof-of concept studies with Eliquis, Xarelto® and enoxaparin in healthy volunteers demonstrated that andexanet alfa immediately reversed the anticoagulation activity of each Factor Xa inhibitor and that the reversal could be sustained. Andexanet alfa has been shown to be well tolerated in clinical studies, which have included more than 100 healthy volunteers, with no thrombotic events or antibodies to Factor Xa or Factor X observed.
A Phase 2 proof-of-concept study with Daiichi Sankyo\'s Factor Xa inhibitor edoxaban is ongoing, and a Phase 2 proof-of-concept study with Portola\'s Factor Xa inhibitor betrixaban is planned.
Financial terms: Under this non-exclusive collaboration agreement, Portola will receive an upfront payment and is eligible to receive additional development and regulatory milestone payments. Portola retains full, worldwide commercial rights to andexanet alfa, for which Portola is pursuing an Accelerated Approval pathway.
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