Atrial Fibrillation (AFib) Support Group
Atrial fibrillation (AF or afib) is an abnormal heart rhythm (cardiac arrhythmia) which involves the two small, upper heart chambers (the atria). Heart beats in a normal heart begin after electricity generated in the atria by the sinoatrial node spread through the heart and cause contraction of the heart muscle and pumping of blood.
From Medscape 10-1-2014
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[1].
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.
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[1].
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.
CardioBuzz: Update on Antidotes for New Oral Anticoagulants
Published: Nov 10, 2014
http://www.medpagetoday.com/Cardiology/Prevention/48497
Aripazine (PER977, ciraparantag)
What is the drug? Aripazine is a synthetic small molecule (D-arginine compound) that has broad activity against various old (heparin, low-molecular-weight heparin) and new oral anticoagulants (dabigatran [Pradaxa], rivaroxaban [Xarelto], apixaban [Eliquis], and edoxaban [Savaysa; not yet FDA approved for any indication]). It binds to the anticoagulants through noncovalent hydrogen bonding and charge-charge interactions. It is being developed by Perosphere.
What anticoagulant drugs might it reverse? Apixaban, edoxaban, rivaroxaban, dabigatran, heparin, low-molecular-weight heparin (LMWH).
Clinical trial status: This week's NEJM reports -- as a letter-to-the editor -- a study in which 80 healthy volunteers received one dose of the new oral anticoagulant edoxaban, followed by intravenous PER977 at various doses. Whole-blood clotting times that were prolonged as expected with edoxaban markedly shortened (to within 10% above the pre-edoxaban baseline value) within 10 minutes after dosing with PER977. Another healthy volunteer study is presently ongoing.
Andexanet (PRT064445)
What is it? Recombinant, modified factor Xa molecule that is being developed as a direct reversal agent for patients receiving a factor-Xa inhibitor who suffer a major bleeding episode or who require emergency surgery. It sort of sops up the anti-Xa anticoagulant, making a patient's own factor Xa again available to participate in the coagulation process. The drug is being developed by Portola.
What anticoagulant drugs might it reverse? Apixaban, edoxaban, rivaroxaban.
Clinical trial status: Healthy volunteer studies to evaluate the ability of andexanet to reverse the effects of several anticoagulant drugs on laboratory tests are presently ongoing.
Idarucizumab (BI 655075)
What is it? It is a humanized antibody fragment directed against dabigatran; generated from mouse monoclonal antibody against dabigatran; humanized and reduced to a FAb fragment. It is being developed by Boehringer-Ingelheim.
What anticoagulant drugs might it reverse? Dabigatran.
Clinical trial status: A phase III study of patients on dabigatran with major bleeding or needing emergency is ongoing. Three phase I studies to determine the effect of idarucizumab on coagulation tests in dabigatran-treated healthy volunteers have been completed.
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