SOUTH SAN FRANCISCO, CA--(Marketwire - March 30, 2012) - Portola Pharmaceuticals, Inc. today announced that it has begun enrollment of patients in its pivotal Phase 3 APEX study, which is evaluating betrixaban, an oral, once-daily Factor Xa inhibitor, for hospital and post-discharge prevention of venous thromboembolism (VTE) in high-risk acute medically ill patients.
"Globally each year more than 150,000 of the 20 million hospitalized patients with diseases such as congestive heart failure, stroke, infection and cancer survive their medical condition but die of a pulmonary embolism, yet there are no approved therapies for the high-risk post-hospital period," said William Lis, chief executive officer of Portola. "The APEX study is designed to advance betrixaban as the first anticoagulant approved for both hospital and post-discharge prevention of fatal blood clots in acute medically ill patients."
"The APEX study is an important trial in the field of thrombosis," said Alexander Cohen, M.D., co-principal investigator of the APEX study and honorary consultant vascular physician at King's College Hospital in London. "The recent clinical trials that we have conducted with other agents have not fully clarified the role of extended VTE prophylaxis in acute medically ill patients. Betrixaban's unique properties, the trial design and high-risk population of the APEX study may help to better address the need for extended-duration prophylaxis in acute medically ill patients."
The first patients were enrolled in the study by John Pullman, M.D., of Mercury Street Medical Group and Big Sky Clinical Research in Butte, Mont., and Seth Baker, D.O., of G&G Research, Inc. in Vero Beach, Fla.
The acute medically ill market represents a large commercial opportunity. It accounts for an estimated 25 percent of the $15 to $20 billion projected 2020 worldwide anticoagulation market, or as much as $4 billion. VTE is a common complication in acute medically ill patients and is associated with a high risk of mortality. Recent large cohort studies that specifically evaluated the post-hospitalization period revealed that the rate of symptomatic VTE more than doubles over the first 21 days post-discharge and is associated with a five-fold increase of fatal pulmonary emboli (PE) between days 10 and 35 post-hospital discharge. However, no anti-coagulants have demonstrated a definitive net clinical benefit for prevention of VTE in the hospital and the period immediately following hospital discharge.
In addition to initiating the APEX study, Portola is preparing to submit an Investigational New Drug (IND) application to the U.S. Food and Drug Administration for PRT064445 in order to begin clinical studies. PRT06445 is a one-of-a-kind reversal agent for oral and injectable Factor Xa inhibitors and low molecular weight heparins and a companion product to betrixaban. Portola plans to build a large hospital-based thrombosis franchise with these two agents.
About Betrixaban and the APEX Study
Betrixaban is an oral small molecule that directly inhibits the activity of Factor Xa, an important validated target in the blood coagulation pathway. A once-daily, oral Factor Xa inhibitor, betrixaban has unique properties compared with other agents in the Factor Xa class. These include a half-life suitable for once-daily dosing, a low level of clearance through the kidney, and lack of metabolism through the CYP pathway. In vivo studies show that the anticoagulative effect of betrixaban can be reversed with PRT4445, Portola's universal Factor Xa inhibitor.
APEX (Acute Medically Ill VTE Prevention with Extended Duration Betrixaban Study) is a randomized, double-blind, active-controlled, multicenter, multinational trial that will compare extended-duration betrixaban (35-42 days) with standard of care enoxaparin, a low molecular weight heparin. The global trial is expected to enroll approximately 6,850 patients at 300 sites. The primary objective of the trial is to demonstrate the superiority of extended-duration anticoagulation with betrixaban over standard of care enoxaparin.
About PRT4445 (Factor Xa Inhibitor Antidote)
The use of Factor Xa inhibitors and low molecular weight heparins (indirect Factor Xa inhibitors) 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. Although bleeding events occur infrequently (1-4 percent in clinical studies), the number of bleeds globally will be significant due to the large number of patients receiving these agents. The cost to treat each patient can range from $15,000 to $42,000 in direct medical expenses. Currently, no agents have been studied or approved to reverse the activity or associated bleeding in patients using oral Factor Xa inhibitors.
PRT4445 is a novel recombinant Factor Xa inhibitor antidote and is the only agent designed to specifically bind and neutralize all Factor Xa inhibitors (direct and indirect) to restore normal haemostatic function if a bleeding event occurs. Once the IND for PRT4445 is submitted and becomes effective, Portola plans to initiate a Phase 1a single ascending dose safety and tolerability trial followed by a proof-of-concept Phase 1b trial to demonstrate the safety of PRT4445 and its ability to reverse the anticoagulation of multiple direct and indirect 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, a recombinant Factor Xa inhibitor antidote and companion product to betrixaban. 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, PRT062607, 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.