Antidote to factor Xa inhibitors exhibits efficacy in patients with major bleeding

Twelve patients (18%) experienced thrombotic events—1 with myocardial infarction, 5 with stroke, 7 with deep-vein thrombosis, and 1 with pulmonary embolism. (Some patients had more than 1 event.)

“This rate of events is not unexpected, considering the thrombotic potential of the patients and the fact that, in most of them, anticoagulation was discontinued at the time of bleeding and not restarted,” Dr Connolly said.

Four patients had a thrombotic event within 3 days of andexanet alfa treatment, and the rest occurred between 4 days and 30 days.

Eighteen patients (27%) resumed anticoagulant therapy within 30 days. One of the 12 patients with a thrombotic event restarted anticoagulation at a therapeutic dose before the event. One other patient received prophylactic doses of enoxaparin before developing a deep-vein thrombosis.

There were 10 deaths (15%), 6 due to cardiovascular events.

Andexanet alfa development

Andexanet alfa is being developed as a reversal agent for apixaban, rivaroxaban, edoxaban, and enoxaparin. Andexanet alfa is intended to be used when reversal of anticoagulation is needed due to life-threatening or uncontrolled bleeding.

The drug is under review by the US Food and Drug Administration (FDA) and the European Medicines Agency. The FDA recently issued a complete response letter regarding the biologics license application for andexanet alfa.

Portola said it plans to meet with the FDA as soon as possible to resolve the outstanding questions in the letter and determine the appropriate next steps.