Mixed findings have been reported from the phase 3 APEX (Acute Medically Ill VTE Prevention With Extended-Duration BetriXaban) study, which evaluated the superiority of extended-duration anticoagulation with oral betrixaban (Portola Pharmaceuticals) compared with standard-of-care anticoagulation with injectable enoxaparin (Lovenox, Sanofi) for the prevention of venous thromboembolism (VTE) in acute medically ill patients. These are patients who are hospitalized for serious common medical conditions, such as heart failure, stroke, infection, and pulmonary disease.
Betrixaban directly inhibits the activity of factor Xa, an important target in the blood coagulation pathway, to prevent thrombosis.
The APEX trial was designed to assess the relative risk in the composite endpoint of ultrasound-detected (asymptomatic) proximal deep venous thrombosis (DVT), symptomatic DVT, nonfatal pulmonary embolism, or VTE-related death in high-risk, acute medically ill patients treated with oral betrixaban for 35 to 47 days compared with patients receiving standard-of-care preventive anticoagulation with injectable enoxaparin, dosed for six to 14 days. The study enrolled 7,513 subjects worldwide.
The primary efficacy and safety analyses involved three patient groups. Cohort 1 consisted of patients with elevated D-dimer levels (62% of the overall study population); cohort 2 consisted of patients with elevated D-dimer levels or advanced age (greater than or equal to 75 years) (91% of the overall study population); and cohort 3 consisted of the overall study population.
Cohort 1 achieved a P value of 0.054, which did not meet the threshold for statistical significance. Cohort 2 and the overall study population achieved P values of 0.029 and 0.006, respectively. There was no statistical difference in major bleeding between the betrixaban and enoxaparin arms in any of the patient groups. The number of fatal bleeds was balanced between the two arms, and the number of intracranial hemorrhages was numerically lower in the betrixaban arm.
Although more than half of VTE events occur after patients have been discharged from the hospital, no anticoagulant, including any of the marketed oral factor Xa inhibitors, is approved for VTE prophylaxis both in the hospital setting and during the extended post-discharge period.
Source: Portola Pharmaceuticals; March 24, 2016.