Betrixaban Approved for Prevention of VTE

Betrixaban was approved by the US FDA despite missing its primary endpoint in the APEX study.

The US Food and Drug Administration (FDA) has approved betrixaban (Bevyxxa, Portola Pharmaceuticals), an oral factor Xa inhibitor administered once daily, for the prevention of thromboembolic complications in patients hospitalized for acute medical illness who are at risk for venous thromboembolism (VTE) due to restricted mobility and other risk factors.

Despite joining a number of factor Xa inhibitors already approved by the FDA for a similar indication, including apixaban (Eliquis, Bristol-Myers Squibb), rivaroxaban (Xarelto, Janssen), and edoxaban (Savaysa, Daiichi Sankyo), the approval of betrixaban is likely to generate some controversy given that its large VTE prevention study missed its primary endpoint.

The phase III APEX study, which included 7,513 patients at 450 sites, had a unique study design with distinct cohorts. In cohort 1, which represented 62% of the study population and included patients with elevated D-dimer levels, treatment with betrixaban failed to reduce the primary endpoint—a composite outcome score comprised of either the occurrence of asymptomatic or symptomatic proximal deep vein thrombosis, nonfatal pulmonary embolism, or VTE-related death—when compared with patients treated with enoxaparin.

Based on the trial design, only if betrixaban was superior to enoxaparin in cohort 1 would testing continue in other patient groups, including cohort 2, which was comprised of patients with elevated D-dimer levels or age ≥ 75 years, and the overall study population.

Despite failing to show a statistically significant benefit in cohort 1, investigators proceeded with the secondary analyses and observed an advantage for betrixaban in cohort 2 and in the overall study population.

At the time the top-line results were announced last year, Portola acknowledged their interpretation of the statistical and clinical data would generate “discussions” at the FDA, but said they felt the results from cohort 1 “were sufficiently strong to support a full assessment of cohort 2 and the overall study population.”

Based on the FDA approval, the recommended dose of betrixaban is an initial dose of 160 mg, followed by 80 mg once daily. The recommended duration of treatment is 35 to 42 days.

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