Before approval of andexanet alfa, off‐label treatment with 4‐factor prothrombin complex concentrate (4F‐PCC) was often utilized for the management of life‐threatening hemorrhages associated with oral factor Xa inhibitors. The elimination half- life ranges from four to seven hours. It is approved for use in patients treated with these factor Xa inhibitors when reversal of anticoagulation is needed because of life-threatening or uncontrolled bleeding, according to the company. Distribution. P/0243/2018: EMA decision of 15 August 2018 on the acceptance of a modification of an agreed paediatric investigation plan for andexanet alfa (EMEA-001902-PIP01-15-M03) (PDF/81.69 KB) PK comparability with andexanet alfa in Ondexxya (Generation 2) has not yet been proven. Andexanet alfa also will not have to be used that often, but the potential pool of patients is larger than for idarucizumab. Table 1: Dosing regimens Carpenter E(1), Singh D(2), Dietrich E(3), Gums J(3). Indication under review : For adult patients treated with a direct factor Xa (FXa) inhibitor (apixaban or rivaroxaban) when reversal of anticoagulation is needed due to life-threatening or uncontrolled bleeding. These anticoagulants work by blocking factor Xa, a natural protein that helps the blood to clot. Andexanet alfa is administered as an intravenous bolus at a target rate of approximately 30 mg/min over 15 minutes (low dose) or 30 minutes (high dose), followed by administration of a continuous infusion of 4 mg/min (low dose) or 8 mg/min (high dose) for 120 minutes (see table 1). Es hebt die Wirkung von bestimmten blutgerinnungshemmenden Wirkstoffen auf und wirkt somit als Antidot.In den USA und der EU ist Andexanet alfa für die Behandlung nicht kontrollierbarer Blutungen unter … Intravenous andexanet alfa [coagulation factor Xa (recombinant), inactivated-zhzo; Andexxa®] is a first-in-class recombinant modified factor Xa protein that has been developed by Portola Pharmaceuticals as a universal antidote to reverse anticoagulant effects of direct or indirect factor Xa inhibitors. Tinzaparin. Andexanet alfa is administered via two different dosing regimens, standard and high dose, based on the specific FXa inhibitor, dose, and time since the patient’s last dose of FXa inhibitor. It is given by injection into a vein.. Common side effects include pneumonia and urinary tract infections. 2019;380(14):1326-1335. ... Portola Pharmaceuticals was contacted for information used for United States Food and Drug Administration approval of andexanet alfa. The recently approved reversal agent andexanet alfa has limited data, an unclear safety profile, and imparts a substantial financial burden. ... Approval of a Biological Product for a Serious or Life-threatening Illness. This decision is almost identical to the approval of idarucizumab, a debacle I have discussed previously . Andexanet alfa has been reported to affect the anticoagulant effect of heparin. Andexanet alfa was approved in May 2018, under the brand name ANDEXXA, for the reversal of 2 of FXa inhibitors, apixaban and rivaroxaban, when life-threatening or uncontrolled bleeding occurs. When Ondexxya is given, the anticoagulants attach to andexanet alfa instead, and they are no longer available to block factor Xa. 1050 Y.-A. andexanet alfa (Ondexxya®) is accepted for use within NHSScotland on an interim basis subject to ongoing evaluation and future reassessment. Manufacturer advises avoid. The effects of the therapy with Ondexxya were studied in 352 patients for safety and 167 patients for efficacy . The V d for andexanet alfa is 5.3 ± 2.6 L, approximately equivalent to the blood volume. These anticoagulant drugs disrupt the clotting process by directly inhibiting one of the … Andexanet alfa is a recombinant protein that acts as a decoy for the direct oral FXa inhibitors apixaban and rivaroxaban in the blood. Andexanet alfa does not currently have a marketing authorisation in the UK for reversing anticoagulation. N Engl J Med. Full study report of andexanet alfa for bleeding associated with factor Xa inhibitors. Andexanet alfa (Hersteller: Portola Pharmaceuticals) ist ein strukturell mit dem menschlichen Blutgerinnungsfaktor Faktor Xa verwandtes Protein, das biotechnologisch erzeugt wird. *****Andexanet alfa (Andexxa) was NOT ADDED to the UW Medicine formulary at this time due to unclear risk vs benefit and high cost. Clearance (L/hr) for andexanet alfa is 4.4 ± 1.2 L/hr with low renal elimination. the FDA’s Accelerated Approval pathway.5. References: 1. It has not been found to be useful for other factor Xa inhibitors. The data used to support Accelerated Approval came from 5 pharmacokinetic (PK) and Andexxa FDA Approval History. 1.2 Andexanet alfa is recommended only in research for reversing anticoagulation from apixaban or rivaroxaban in adults with life-threatening or uncontrolled bleeding in the skull (intracranial haemorrhage).. Why the committee made these recommendations. Objective: The purpose of this article is to review the available clinical trial data for andexanet alfa and its role in clinical practice.Data Sources: A MEDLINE/PubMed search was conducted (January 2000 to January 2019) using the keyword andexanet alfa for clinical trials. Andexanet alfa (PRT064445) is a first-in-class human recombinant protein developed as an antidote to direct oral anticoagulants such as apixaban, rivaroxaban, and edoxaban. Andexanet alfa was developed and launched by Portola Pharmaceuticals. Andexanet alfa produced rapid reversal of the anticoagulant effect of apixaban, as measured by anti-Factor Xa activity, which was sustained for the duration of the infusion. Severity of interaction: Severe Evidence for interaction: Anecdotal. “It’s a small fraction of patients that develop major life-threatening bleeding on any of these anticoagulants, but when they do develop bleeding, the consequences can be severe,” Connors said. Elimination. Andexanet alfa is now owned and marketed by Alexion.6 . As a result, andexanet alfa neutralises the anticoagulant effect of these inhibitors. Andexanet alfa was granted accelerated approval for this indication based on the drug’s anti-factor Xa activity in healthy volunteers. Apixaban and rivaroxaban are anticoagulants used for preventing and treating thromboembolism (blood clots). This accelerated approval was based on change in anti-FXa activity from baseline that indicated a reversal of the anticoagulant effect. The approval for andexanet alfa is supported by data from two phase 3 studies (ANNEXA-A, ANNEXA-R) and preliminary data from the phase 3b/4 ANNEXA-4 trial. Siegal DM, Curnutte JT, Connolly SJ, et al. This has led to the off-label use of four-factor prothrombin complex concentrates (4F-PCC) for this indication. Portola Launches European Sales of Ondexxya® (Andexanet Alfa) with First Orders in Europe - Expands Patient Access to the First and Only Factor … In the study, andexanet alfa was well tolerated, with no serious adverse events, thrombotic events, or antibodies to … Connolly SJ, Crowther M, Eikelbloom JW, et al. As a result, andexanet alfa neutralises the anticoagulant effect of these inhibitors. It has been studied in a single arm trial in adults who had acute major bleeding episode within 18 hours after administration of an anticoagulant. Providers should continue to order 4F-PCC (Kcentra) for urgent reversal of anti-Xa inhibitors per UW Medicine guidelines. Andexanet alfa for reversal of factor Xa inhibitor-associated anticoagulation. References of identified articles were searched by hand for additional citations. Andexanet alfa is predicted to affect the anticoagulant effect of tinzaparin. Andexanet alfa, the active substance in Ondexxya, acts as a decoy target for anticoagulants called factor Xa inhibitors such as apixaban and rivaroxaban. Andexanet alfa, the first FDA approved (May 2018) targeted reversal agent for the oral factor Xa inhibitors (Xai), is a recombinant factor Xa modified to lack catalytic activity that binds, sequesters, and neutralizes unbound Xai. The phase 2 and 3 studies of andexanet alfa in healthy adults should also be added here. (INN) andexanet alfa. Last year, the FDA granted andexanet alfa an accelerated approval as a reversal agent for factor Xa inhibitors, but based that decision on a complete lack of useable science. N Engl J Med. Clinical efficacy is based upon reversal of anti-fXa-activity in healthy volunteers and interim results of study in patients with life-threatening bleeding. Andexanet alfa, the first agent shown to reverse the anticoagulant effects of rivaroxaban and apixaban, has been approved by the FDA, according to a May 3 statement from Portola Pharmaceuticals.. Reversal with andexanet alfa has not been compared to standard of care or alternative treatment options, such as 4‐factor prothrombin complex concentrate (4F‐PCC), yet it has become the first‐line agent in many institutions and in national organization guidance documents. Andexanet alfa for the reversal of factor Xa inhibitor activity. 2015;373(25):2413-2424. The effects of the therapy were studied in 352 patients for safety and 167 patients for efficacy. Continued FDA approval of andexanet alfa may be contingent upon post-marketing study results to demonstrate an improvement in hemostasis in patients taking rivaroxaban or apixaban who require reversal of anticoagulation. The approval for andexanet alfa is supported by data from two phase 3 studies (ANNEXA-A, ANNEXA-R) and preliminary data from the phase 3b/4 ANNEXA-4 trial. Heo 1.1 Cay Agreemen a Paten Iation In2014,PortolaPharmaceuticalssignedcommercialsupply … The full data set was presented at the International Society on Thrombosis and Haemostasis (ISTH) 2015 Congress. 3. Andexanet alfa is administered via two different dosing regimens, standard and high dose, based on the specific FXa inhibitor, dose, and time since the patient's last dose of FXa inhibitor. In July 2020, Portola Pharmaceutical was acquired by Alexion. Andexanet alfa, sold under the trade name Andexxa among others, is an antidote for the medications rivaroxaban and apixaban, when reversal of anticoagulation is needed due to uncontrolled bleeding. FDA Approved: Yes (First approved May 3, 2018) Brand name: Andexxa Generic name: coagulation factor Xa (recombinant), inactivated-zhzo Company: Portola Pharmaceuticals, Inc. European Commission Grants Conditional Marketing Authorization for Portola Pharmaceuticals’ Ondexxya™ (andexanet alfa), the First and Only Antidote for the Reversal of … Andexanet alfa was well tolerated, with no serious adverse events, thrombotic events, or antibodies to Factor X or Xa reported. Portola plans to submit a Biologics License Application for andexanet alfa to the FDA Treatment for: Reversal of Anticoagulant Activity of Factor Xa Inhibitors Andexxa (coagulation factor Xa (recombinant), inactivated-zhzo) is a recombinant modified human Factor …