Portola Pharmaceuticals, a biopharmaceutical company developing product candidates that could significantly advance the fields of thrombosis and other hematologic diseases, has executed a supply agreement with Lonza for the commercial manufacturing of andexanet alfa. An FDA-designated breakthrough therapy, andexanet alfa is the only recombinant Factor Xa molecule designed to specifically reverse the effects of oral and injectable Factor Xa inhibitors. It is being developed as an antidote for patients receiving one of these anticoagulants who either suffer from a major bleed or require emergency surgery.

With this global agreement, Portola has secured two commercial manufacturing contracts in order to supply the global market. CMC Biologics will manufacture andexanet alfa for the expected US launch in 2016. To meet anticipated global demand, Lonza will provide large-scale supply approximately 18-24 months following launch.

Andexanet alfa, an FDA-designated breakthrough therapy, is being developed as a universal antidote 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.

Portola is evaluating andexanet alfa in randomized, placebo-controlled phase 3 ANNEXA (Andexanet Alfa a Novel Antidote to the Anticoagulant Effects of fXA Inhibitors) registration studies using pharmacodynamic endpoints agreed to with the FDA, such as anti-Factor Xa inhibitor units, to demonstrate efficacy.

Portola reported statistically significant results from the phase 3 ANNEXA-A study with Bristol-Myers Squibb Company (BMS) and Pfizer Inc.'s direct Factor Xa inhibitor Eliquis (apixaban) administered as an intravenous bolus dose. Another ANNEXA-A study evaluating a longer duration infusion is ongoing. Data from the phase 3 ANNEXA-R study with Bayer HealthCare and Janssen's direct Factor Xa inhibitor Xarelto (rivaroxaban) is expected to be available later this year. ANNEXA-E, the phase 3 study with Daiichi Sankyo's direct Factor Xa inhibitor edoxaban, is expected to begin in 2015. These studies are designed to support the company's BLA filing for Accelerated Approval. As part of the Accelerated Approval process, a phase 3b/4 confirmatory patient study evaluating clinical outcomes with andexanet alfa is planned.

Results from three separate phase 2 proof-of concept studies with Eliquis, Xarelto and enoxaparin, a low molecular weight heparin and indirect Factor Xa inhibitor, 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 phase 1 and 2 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 edoxaban is ongoing, and a Phase 2 proof-of-concept study with Portola's Factor Xa inhibitor betrixaban is planned.

Andexanet alfa, a recombinant modified Factor Xa molecule, has the potential to be a first-in-class antidote to reverse the effects of Factor Xa inhibitors in patients who suffer a major bleeding episode or who require emergency surgery. Andexanet alfa has been designated as a breakthrough therapy by the US Food and Drug Administration. Portola has entered into phase 3 clinical collaboration agreements with all of the manufacturers of direct Factor Xa inhibitors – Bristol-Myers Squibb and Pfizer (Eliquis [apixaban]), Bayer HealthCare and Janssen Pharmaceuticals (Xarelto [rivaroxaban]), and Daiichi Sankyo (edoxaban) – while retaining all commercial rights to andexanet alfa. The Company is currently evaluating andexanet alfa in the phase 3 ANNEXA (Andexanet Alfa a Novel Antidote to the Anticoagulant Effects of fXA Inhibitors) registration studies.

Portola's product candidate in the area of hematologic cancer, cerdulatinib, is an orally available molecule that uniquely inhibits two validated tumor proliferation pathways – spleen tyrosine kinase (Syk) and janus kinase (JAK). It is currently being evaluated in a phase 1/2 proof-of-concept study in patients with B cell leukemias or lymphomas with a focus on genetically-defined subtypes, as well as in patients who have failed therapy due to relapse or acquired mutations.

Lonza is a worldwide leader in global pharmaceutical manufacturing with more than 40 facilities and 10,000 employees worldwide.