Portola Pharmaceuticals has announced results of a study demonstrating that andexanet alfa significantly reduced bleeding in a validated animal model of bleeding using the Factor Xa inhibitor rivaroxaban as the anticoagulant. The reduction in blood loss correlated with reversal of the anticoagulant effects of rivaroxaban as measured by anti-Factor Xa activity, a definitive pharmacodynamic measurement of the anticoagulant activity of Factor Xa inhibitors.
In contrast, the four-factor prothrombin complex concentrate (PCC) Kcentra did not impact bleeding or the anti-Factor Xa coagulation biomarker in the study. The results were presented in an oral session at the International Society on Thrombosis and Haemostasis Congress (ISTH; 20–25 June, Toronto, Canada).
Andexanet alfa, a US Food and Drug Administration (FDA)-designated breakthrough therapy, is a recombinant protein specifically designed to reverse the anticoagulant activity in patients treated with an oral or injectable Factor Xa inhibitor. Andexanet alfa has the potential to be a first-in-class antidote for anticoagulated patients who suffer a major bleeding episode or require emergency surgery. Portola is currently evaluating the antidote in two randomised, placebo-controlled phase 3 ANNEXATM registration studies with apixaban and rivaroxaban and in a phase 4 confirmatory study in patients receiving apixaban, rivaroxaban or enoxaparin who present with an acute major bleed.
“The finding that andexanet alfa significantly reduced blood loss in an animal model of rivaroxaban bleeding while the PCC showed no reversal activity or improvement in bleeding is consistent with other animal model data from studies conducted by Portola and other labs,” said John T Curnutte, executive vice president, research and development, for Portola. “These results distinguish andexanet alfa as the only agent that acts as a Factor Xa inhibitor antidote by binding directly to Factor Xa inhibitors.”
Curnutte added, “Four-factor PCCs are US Food and Drug Administration-approved to reverse the effects of vitamin K antagonists but are not approved to reverse the anticoagulant effects of Factor Xa inhibitors, and no known label-enabling studies are ongoing. Additionally, the FDA and the European Medicines Agency do not view four-factor PCCs as a standard of care therapy in our ongoing phase 4 study of andexanet alfa in anticoagulated patients who present with an acute major bleed.”