![]() ![]() The trial is expected to complete in 2017. A total of 250 patients are expected to be recruited to receive a 1-time IV administration of idarucizumab 5 g. A phase 3 study evaluating idarucizumab in patients in actual clinical settings, RE-VERSE AD began this year. Idarucizumab is a selective and specific monoclonal antibody fragment being studied as an antidote to dabigatran. It is anticipated that a BLA filing with FDA will occur in 2015. A phase 3b/4 study will be initiated to evaluate clinical outcomes before filing the biologics license application (BLA). 7Īndexanet alfa has been designated as a breakthrough therapy by FDA, and plans are under way to pursue an accelerated approval pathway. In phase 2 studies, andexanet alfa has been shown to reverse the anticoagulant activity of enoxaparin (a low-molecular weight heparin that indirectly acts on factor X and factor IIa), rivaroxaban, and apixaban. Two additional phase 3 studies using andexanet alfa as an antidote for rivaroxaban and edoxaban (investigational factor Xa inhibitor, Daiichi Sankyo) are ongoing or planned. ![]() Mild infusion reactions were reported by 3 volunteers. No serious or thrombotic adverse events were reported. The second part of the study will test a 400-mg IV bolus followed by a continuous infusion of 4 mg/min for 120 minutes, with results expected in early 2015. The anticoagulant activity of apixaban was reversed by 94% ( P<.0001) 2 to 5 minutes after the bolus dose of andexanet, measured by the biomarker end point, anti-factor Xa activity. A total of 24 healthy volunteers were randomized to an intravenous (IV) 400-mg bolus dose of andexanet, and 9 patients were given placebo. Initial results have been released from the phase 3 trial, ANNEXA-A (Andexanet Alfa a Novel Antidote to the Anticoagulant Effects of fXA Inhibitors–Apixaban). Andexanet alfa acts as a factor Xa decoy that targets and sequesters with high specificity both direct and indirect factor Xa inhibitors in the blood. The first agent, andexanet alfa, is a recombinant, modified factor Xa molecule. There are, however, currently 3 anticoagulant reversal agents (antidotes) in phase 2 or 3 clinical trials. Additionally, they can be prothrombotic, causing problems if too much is given. Data on these reversal therapies are limited and have been studied only in animal models or healthy volunteers. 3įresh frozen plasma, prothrombin complex concentrates (PCCs), and PCCs with added activated factor VIIa have been used to try to reverse the anticoagulant effects and stop bleeding in patients on factor Xa and IIa inhibitors. It is estimated that between 1% and 5% of patients taking factor Xa inhibitors may experience a spontaneous major bleed or require emergency surgery. 2 One significant drawback of using the NOACs, however, is the current lack of an antidote to reverse the anticoagulant effects of these agents in the case of a major spontaneous bleed or prior to emergency surgery. It is estimated that these 3 agents will constitute about 36% (by prescription volume) of the US anticoagulant market by 2020. An additional agent, dabigatran etexilate mesylate ( Pradaxa, Boehringer Ingelheim) inhibits thrombin (factor IIa) and has the same advantages as rivaroxaban and apixaban. 1 They offer advantages compared to warfarin such as a rapid onset of action, no dietary modifications, fewer drug–drug interactions, and do not require routine coagulation monitoring.ĪHA: Rivaroxaban linked to fewer hospitalization days compared to warfarin in NVAF patientsīoth rivaroxaban and apixaban are direct factor Xa inhibitors. Over the past 4 quarters, rivaroxaban (Xarelto, Bayer/ Johnson & Johnson) and apixaban (Eliquis, Bristol-Myers Squibb/ Pfizer) were in the top 20 of fastest-growing drugs in the United States. The use of new oral anticoagulants (NOACs) continues to increase. ![]()
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