The US Food and Drug Administration (FDA) has granted Fast Track designation to Portola Pharmaceuticals' betrixaban for extended-duration prevention of venous thromboembolism (VTE), or blood clots, in acute medically ill patients (i.e., those who are hospitalised for serious medical conditions, such as heart failure, stroke, infection and pulmonary disease).

Betrixaban is an investigational oral anticoagulant that directly inhibits the activity of Factor Xa, an important validated target in the blood coagulation pathway, to prevent life-threatening thrombosis.

Portola is currently evaluating betrixaban in the global, pivotal, 7,500-patient phase 3 APEX (Acute Medically Ill VTE Prevention with Extended Duration Betrixaban) study for the prevention of VTE in acute medically ill patients. The company expects to complete patient enrollment in APEX by the end of 2015 and report top-line data in the first quarter of 2016. If the trial is successful, the company expects to submit a New Drug Application (NDA) later in 2016 under the Fast Track designation.

The FDA’s Fast Track process is designed to facilitate the development and expedite the review of drugs used to treat serious conditions and fill an unmet medical need. Fast Track designation enables a company to have early and frequent communication with the FDA throughout the drug development and review process, often leading to earlier drug approval.

“FDA’s Fast Track designation of betrixaban recognises the unmet medical need in the prevention of VTE in acute medically ill patients. Importantly, it raises public awareness of this life-threatening condition in a large, underserved patient population. Betrixaban has the potential to become the first anticoagulant approved for extended-duration prevention of VTE,” said John T. Curnutte, M.D., Ph.D., executive vice president, research and development, for Portola. “We’re now focused on completing the APEX trial and reporting results in early 2016.”

The phase 3 APEX Study is evaluating the superiority of extended-duration anticoagulation with oral betrixaban (for 35-42 days) compared with standard of care anticoagulation with injectable enoxaparin (for up to 14 days) for the prevention of VTE in acute medically ill patients. The study is being conducted at 450 clinical sites worldwide. APEX is using a biomarker-based trial design to identify and enroll patients who are at highest risk of VTE and most likely to benefit from betrixaban – specifically those with an elevated level of D-dimer (a protein fragment present after a blood clot has developed) and those over age 75. The APEX study is the only biomarker-based phase 3 study for hospital-to-home prophylaxis of VTE in acute medically ill patients. It is also the only pivotal thrombosis trial evaluating a single anticoagulant for VTE prophylaxis in both the in-hospital and post-discharge settings.

Betrixaban has distinct properties that may allow it to demonstrate clinical benefit without the significant imbalance in the risk of fatal bleeding seen with other agents in the class. These include a 19-25-hour half-life for once-daily dosing; a low peak-to-trough drug concentration ratio that minimizes anticoagulant variability; low renal clearance; and no significant CYP3A4 metabolism, which may reduce the risk of drug-drug interactions.