A supplemental new drug application has been submitted to the US Food and Drug Administration (FDA) for 10-mg rivaroxaban as a treatment to reduce the risk of recurrent venous thromboembolism (VTE) after at least six months of standard anticoagulation therapy.
Paul Burton, MD, PhD
A supplemental new drug application has been submitted to the US Food and Drug Administration (FDA) for 10-mg rivaroxaban (Xarelto) as a treatment to reduce the risk of recurrent venous thromboembolism (VTE) after at least six months of standard anticoagulation therapy, according to a statement from Janssen, the company developing the blood thinner.
The application was based on data from the phase 3 EINSTEIN CHOICE study, which showed a reduction in recurrent VTE risk for rivaroxaban versus aspirin. Janssen is seeking approval for the 10-mg prophylactic dose of rivaroxaban, which reduced the risk of a recurrent event by 74% compared with aspirin (hazard ratio [HR], 0.26; 95% CI, 0.14-0.47; P <.001).
A 20-mg dose of prophylactic rivaroxaban is currently approved for VTE. In the EINSTEIN CHOICE study, the 20-mg dose demonstrated a 66% reduction in the risk of a recurrent VTE event (HR, 0.34; 95% CI, 0.20-0.59; P <.001).
“For those people who have had a VTE and stop anticoagulant therapy, as many as 10% of them will experience another VTE within one year and 20% within three years,” Paul Burton, MD, PhD, FACC, Vice President, Medical Affairs, Janssen, said in a statement. “Our hope is to offer two dose options for continued treatment with Xarelto to the many people at risk of having another VTE.”
In the double-blind study, 3365 patients were randomized to receive aspirin at 100 mg (n = 1131) or rivaroxaban at 20 mg (n = 1107) or 10 mg (n = 1127). Patient characteristics were similar across each arm, with approximately 60% of patients having a provoked VTE index event. All patients had received anticoagulants for 6 to 12 months, including dabigatran, rivaroxaban, apixaban, or edoxaban.
The primary efficacy endpoint assessed the rate of symptomatic, recurrent fatal or nonfatal VTE, this also included patients with an unexplained death when pulmonary embolism could not be ruled out. The primary safety endpoint was focused on major bleeding events.
Overall, 1.5% of patients in the rivaroxaban 20-mg arm experienced an event that met the criteria for the primary endpoint, as did 1.2% in the 10-mg arm. In the aspirin arm, 4.4% of patients experienced an event. Neither dose of rivaroxaban was superior when compared with each other (HR, 1.34; 95% CI, 0.65-2.75; P = .42).
Major bleeding occurred in 0.5% and 0.4% of patients in the 20-mg and 10-mg rivaroxaban groups, respectively. This was compared with 0.3% of those in the aspirin arm. Clinically relevant nonmajor bleeding was seen in 2.7% and 2.0% of patients in the 20-mg and 10-mg arms, respectively, and for 1.8% of those in the aspirin group.
The FDA typically assigns a review designation within 60 days. After this period, the standard review takes 10 months, placing a decision in April 2018.
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