SOUTH SAN FRANCISCO, CA--(Marketwire - June 15, 2012) - Portola Pharmaceuticals, Inc. today announced enrollment of subjects in the second cohort of its Phase 1 study of PRT4445, the first universal Factor Xa inhibitor antidote in clinical development. PRT4445 is a recombinant biologic designed to reverse the anticoagulant activity of oral and injectable Factor Xa inhibitors in patients suffering life-threatening bleeds or requiring urgent surgery. No agents are approved to specifically reverse the activity of oral Factor Xa inhibitors. Current strategies for mitigating serious bleeding in patients taking Factor Xa inhibitors include the administration of coagulation factors such as recombinant Factor VIIa or blood-derived prothombin complex concentrates, which have not been shown to be effective and are known to have prothrombotic risk.
PRT4445 is a companion product to betrixaban, a novel, oral, once-daily Factor Xa inhibitor. Portola is evaluating betrixaban in its global, pivotal Phase 3 APEX Study to show superiority to the current standard of care for hospital and post-discharge prevention of venous thromboembolism (VTE) in acute medically ill patients, a multi-billion dollar indication for which there are no approved therapies for use post hospital discharge.
"Factor Xa inhibitors have been shown to be a major advancement over current standard therapies, such as warfarin and enoxaparin. However, for patients taking these agents who are bleeding or require urgent surgery, physicians need a rapid reversal agent to return patients to normal hemostasis. Our goal is to bring to market the first antidote for both oral and injectable Factor Xa inhibitors to reverse their anticoagulant activity, when needed, and reduce the risk of life-threatening bleeds and associated costs," said Michael M. Kitt, M.D., senior vice president and chief medical officer of Portola. "With the initiation of our Factor Xa inhibitor antidote clinical program and the Phase 3 study of betrixaban earlier this year, Portola now has in clinical development two unique hospital-based drugs in the field of thrombosis with the potential to establish a new standard of care."
The Phase 1 single ascending dose safety and tolerability study of PRT4445 will include approximately 40 healthy volunteers and will be conducted in the United States. It will be followed this fall by a clinical proof-of-concept study to demonstrate the safety of PRT4445 and its ability to reverse the anticoagulation activity of Factor Xa inhibitors at steady state in subjects taking one of multiple Factor Xa inhibitors.
Need for Factor Xa Inhibitor Antidote
The use of Factor Xa inhibitors, including low molecular weight heparins, is projected to grow and exceed 20 million patients by the year 2020. The major limitation of these agents is bleeding, which is a rare but potentially life-threatening and costly complication. About 300,000 U.S. patients taking these drugs will experience a life-threatening bleed, and 3 million U.S patients will be at risk for bleeding because they require surgery. Although bleeding events occur infrequently (1-4 percent in clinical studies), the number globally will be significant due to the large number of patients receiving these agents. The cost to treat a bleeding case can range from $15,000 to $42,000 in direct medical expenses -- due in part to non-specific, incomplete and difficult-to-administer reversal strategies that can result in a pro-thrombotic state. Currently, no agents are approved to specifically reverse the activity of oral Factor Xa inhibitors.
About Portola Pharmaceuticals, Inc.
Portola Pharmaceuticals discovers and develops innovative therapeutics based on targets with established proof of concept that are designed to provide significant advances over current treatments for cardiovascular and autoimmune/inflammatory diseases. Portola scientists have successfully collaborated for over 15 years on the discovery and development of novel small molecule agents targeting platelets, coagulation pathways and protein kinases. In thrombosis, Portola is independently developing betrixaban and PRT4445. In inflammation, Portola is collaborating with Biogen Idec to develop and commercialize highly selective, novel oral Syk inhibitors for the treatment of various autoimmune and inflammatory diseases, including rheumatoid arthritis and systemic lupus erythematosus. The collaboration's lead molecule, PRT2607, has been shown to be a highly potent and specific oral inhibitor of Syk. Portola's broad chemistry capability also has led to the discovery of dual inhibitors of Syk and Janus Kinase (JAK) for chronic autoimmune indications and oncology. For additional information, visit www.portola.com.