Novel oral anticoagulants (NOACs), which include Factor Xa inhibitors, are an important advance in the prevention and treatment of thromboembolic disease. However, there is a significant unmet medical need for an improved NOAC for the acute medically ill patient population. The current in-hospital standard of care has limitations and is associated with increased bleeding. Additionally, no anticoagulant is approved for use after hospital discharge when the majority of life-threatening clots occur. Recent real-world patient data and earlier clinical trial results have shown that annually between 1-4 percent of the millions of patients who are treated with Factor Xa inhibitors may experience major bleeding. Yet, there is no approved antidote for these agents.
Portola Pharmaceuticals is working to address the safety issues, specifically bleeding, that limit the use of NOACS with its dual approach.
First, Portola's oral Factor Xa inhibitor, betrixaban, currently in Phase 3 clinical development, has distinct properties that may allow it to reproduce the established efficacy of the Factor Xa inhibitor class without the significant increase in major bleeding that has been observed in this patient population with other agents.
Second, Portola is developing andexanet alfa, an FDA-designated breakthrough therapy in Phase 3 studies, to treat bleeding episodes. As a first-in-class recombinant, modified Factor Xa molecule, andexanet alfa acts as a decoy to allow for the restoration of normal hemostatic processes.
John T. Curnutte will describe the scientific and clinical advances these two programs represent. He will also review another agent in development, cerdulatinib. This oral Syk/JAK kinase inhibitor, currently being evaluated in a Phase 1/2 study, has potential for activity in leukemias and lymphomas.
Dr. John T. Curnutte joined Portola as Executive Vice President, Research and Development, in 2011. Prior to joining Portola, he served as Chief Executive Officer of 3-V Biosciences, a private start-up company founded in 2007 with the goal of developing host-directed antiviral small molecules. Before that, he served as President at Schering-Plough Biopharma (formerly DNAX Research Institute; now Merck Research Laboratories) where he led the drug discovery and early development efforts for biologic therapeutics. During his time with Schering-Plough, eight therapeutic entities progressed into development, including five small molecules and one gene therapy construct, in the immunology and oncology therapeutic areas. Earlier in his career, he held several senior management positions at Genentech during which he oversaw that company's immunology discovery program.
Prior to Genentech, Dr. Curnutte was a tenured faculty member at The Scripps Research Institute, pursuing basic and clinical research in inflammation biochemistry and the molecular genetics of congenital immune deficiencies. He received an undergraduate degree in biochemistry and molecular biology from Harvard University, an M.D. and a Ph.D. in biological chemistry from Harvard Medical School. He is currently an adjunct clinical professor of pediatrics at the Stanford University School of Medicine and a member of the medical staff, where he continues to consult on patients with primary immunodeficiencies.