SAN FRANCISCO, CA – A phase 3 study designed to test an antidote to the factor Xa inhibitor class of novel anticoagulants met its primary efficacy end point, according to an announcement from Portola Pharmaceuticals.
An intravenous bolus of andexanet alfa "immediately and significantly" reversed the anticoagulation of apixaban (Eliquis, Bristol-Myers Squibb/Pfizer) in the ANNEXA-A study, the company reported. In total, 33 healthy volunteers in the study were treated with apixaban 5 mg twice daily for four days and then randomized to andexanet alfa 400 mg or placebo.
The results of ANNEXA-A is slated for presentation on Monday, November 17, 2014 during the American Heart Association 2014 Scientific Sessions in Chicago, IL.
Given the positive results, Portola plans to file an application with the US Food and Drug Administration (FDA) for accelerated approval.
Currently, the FDA has designated andexanet alfa a breakthrough therapy, which is meant to help accelerate the development and review of drugs for serious or life-threatening conditions. This is awarded when early evidence suggests the agent represents a substantial improvement over existing therapies on one or more significant end points. Idarucizumab , an investigational antidote for the oral thrombin inhibitor dabigatran etexilate mesylate (Pradaxa, Boehringer Ingelheim), also has FDA breakthrough status.
Antidotes to the new generation of oral anticoagulants, of which none are yet available, would be extremely valuable for managing otherwise-uncontrolled bleeding. Unlike bleeds related to warfarin, which can be reversed using low-dose vitamin K1 or the newer product, prothrombin complex concentrate (human) (Kcentra, CSL Behring), there are no currently approved agents for reversing bleeds due to dabigatran or the factor Xa inhibitors or reversing their anticoagulant effects in the case of emergency surgery.
The company is currently testing the antidote on other factor Xa inhibitors and plans to report additional data in studies of andexanet alfa on rivaroxaban (Xarelto, Bayer Pharma/Janssen Pharmaceuticals), edoxaban (Lixiana, Daiichi-Sankyo), and betrixaban (Portola Pharmaceuticals/Merck). It is also testing the antidote in patients treated with enoxaparin (Lovenox, Sanofi).
The second part of ANNEXA-A study is also under way. Similar in design to the first, the intravenous bolus of andexanet alfa will be followed by a continuous infusion of 4 mg/min or placebo for two hours. Results of this study will be available in 2015.
Heartwire from Medscape © 2014 Medscape, LLC
Cite this: Positive Results for Factor Xa Inhibitor Antidote: ANNEXA-A - Medscape - Oct 01, 2014.