Product Pipeline

Betrixaban: Long-acting, oral, direct Factor Xa Inhibitor

Description

Betrixaban is an oral small molecule that directly inhibits the activity of Factor Xa, an important validated target in the blood coagulation pathway.

Key Characteristics

Betrixaban has been specifically designed for chronic, once-a-day treatment. It has a half-life that supports true, once-daily dosing and a low peak-to-trough drug concentration ratio that minimizes anticoagulant variability. Betrixaban is primarily eliminated unchanged in the bile and has been studied in patients with all degrees of renal function, including those with severe renal impairment (excluding dialysis patients). Betrixaban is minimally metabolized through the Cytochrome 450 enzyme system, which may result in low potential for CYP-related drug interactions. Betrixaban is reversible with PRT0644545, a universal Factor Xa inhibitor antidote that Portola is developing as a companion product.

Potential Indications

Treatment or prevention of life-threatening blood clots (venous thromboembolism; VTE) in acute medically ill patients

Clinical Development

In 2007, positive top-line results from EXPERT were published in The Journal of Thrombosis and Haemostasis. This randomized, multi-center, Phase 2 in-hospital efficacy and safety study of the prevention of VTE compared betrixaban with enoxaparin in 215 patients undergoing knee replacement surgery. Portola plans to initiate a Phase 3 betrixaban program to prevent VTE in acute medically ill patients in 2012.

The safety and tolerability of betrixaban for stroke prevention was evaluated in 508 patients with atrial fibrillation in the Phase 2 EXPLORE-Xa dose-ranging study. Results were presented during a late-breaking session at the American College of Cardiology’s 59th Annual Scientific Session in March 2010. The data showed that a once-daily dose of oral betrixaban, given to patients with non-valvular atrial fibrillation or atrial flutter and at least one risk factor for stroke, reduced the incidence of major and clinically relevant non-major bleeds compared to dose-adjusted warfarin. In August 2010, additional pharmacodynamic data from a pre-specified analysis of EXPLORE-Xa showed a concentration dependent relationship and provided further evidence for the anticoagulant activity of betrixaban across all three doses studied in the clinical trial. The additional pharmacodynamic analysis provides information for dose selection for Phase 3 evaluation of betrixaban.