b'B:16"T:15.75"S:14.75"Available on theVA National Therst and only speci c reversal agent for Eliquis (apixaban)- or Xarelto (rivaroxaban)-treatedFormularypatients with life-threatening or uncontrolled bleeding.1 2 MINUTES 1 *IN JUST sustained throughout the 2-hour IV infusion.following bolus and 93% decrease in anti-FXa activity in patients with acute major bleeding taking Eliquis and Xarelto 1 * ANNEXA-A and ANNEXA-R were two Phase 3 studies designed to establish the ef cacy and safety of ANDEXXA for the reversal of anticoagulation with apixaban or rivaroxaban in older, healthy volunteers vs placebo. The primary endpoint of both studies was mean percent change in anti-FXa activity, from baseline to nadir, for the low-dose and high-dose regimens of bolus followed byS:9.75" T:10.75" B:11"continuous infusion. In ANNEXA-A and ANNEXA-R, 23/31 and 26/39 patients received ANDEXXA, respectively.1From baseline to nadir.1 ANNEXA-4 was a Phase 3b/4 multinational, prospective, single-arm, open-label study in which ANDEXXA was administered to patients (N=352) taking FXa inhibitors who presented with acute major bleeding. A primary endpoint was percent change from baseline in anti-FXa activity. Nadir was measured between 5 minutes after bolus until the end of the infusion1 SELECT IMPORTANT SAFETY INFORMATION.INDICATION Re-elevation or Incomplete Reversal of Anti-FXa Activity ImmunogenicityANDEXXA (coagulation factor Xa (recombinant), inactivated-zhzo) is a recombinant modified human factor Xa (FXa) protein indicated for patientsThe time course of anti-FXa activity following ANDEXXA administrationAs with all therapeutic proteins, there is the potential for treated with rivaroxaban or apixaban, when reversal of anticoagulation is needed due to life-threatening or uncontrolled bleeding. was consistent among the healthy volunteer studies and the ANNEXA-4immunogenicity. Using an electrochemiluminescence (ECL)-based This indication is approved under accelerated approval based on the change from baseline in anti-FXa activity in healthy volunteers. Anstudy in bleeding patients. Compared to baseline, there was a rapidassay, 145 ANDEXXA-treated healthy subjects were tested for improvement in hemostasis has not been established. Continued approval for this indication may be contingent upon the results of studies thatand substantial decrease in anti-FXa activity corresponding to theantibodies to ANDEXXA as well as antibodies cross-reacting with demonstrate an improvement in hemostasis in patients.ANDEXXA bolus. This decrease was sustained through the end of theFactor X (FX) and FXa. Low titers of anti-ANDEXXA antibodies were Limitations of Use ANDEXXA continuous infusion. The anti-FXa activity returned to theobserved in 26/145 healthy subjects (17%); 6% (9/145) were first ANDEXXA has not been shown to be e ective for, and is not indicated for, the treatment of bleeding related to any FXa inhibitors other thanplacebo levels approximately two hours after completion of a bolus orobserved at Day 30 with 20 subjects (14%) still having titers at the last apixaban or rivaroxaban. continuous infusion. Subsequently, the anti-FXa activity decreased at atime point (Days 44 to 48). To date, the pattern of antibody response WARNINGS AND PRECAUTIONS rate similar to the clearance of the FXa inhibitors. in patients in the ongoing ANNEXA-4 study has been similar to that SELECT IMPORTANT SAFETY INFORMATION Thromboembolic and Ischemic Risks Seventy-one subjects were anticoagulated with apixaban and hadobserved in healthy volunteers. Of the 236 subjects with available The thromboembolic and ischemic risks were assessed in 352 bleedingbaseline levels of anti-FXa activity 150 ng/mL. Nineteen subjects whosamples, 6.8% (16/236) had antibodies against ANDEXXA. None of subjects who received ANDEXXA. Of the 63 subjects who experiencedwere anticoagulated with rivaroxaban had elevated baseline anti-FXathese anti-ANDEXXA antibodies were neutralizing. No neutralizing WARNING: THROMBOEMBOLIC RISKS, ISCHEMIC RISKS,a thrombotic event, the median time to first event was 7 days, andactivity levels 300 ng/mL. Forty-eight of the 71 apixaban-treatedantibodies cross-reacting with FX or FXa were detected in healthy CARDIAC ARREST, AND SUDDEN DEATHS 21 subjects experienced the event within the first three days. A totalsubjects (68%) experienced a 90% decrease from baseline anti-FXasubjects (0/145) or in bleeding patients (0/209) to date.See full prescribing information for complete boxed warning of 63 (18%) experienced 88 thromboembolic or ischemic events. Ofactivity after administration of ANDEXXA. Ten of the 19 rivaroxabanTo report SUSPECTED ADVERSE REACTIONS, call 1-866-777-5947 Treatment with ANDEXXA has been associated with serious andthe 352 subjects who received ANDEXXA, 223 received at least onesubjects (53%) experienced a 90% decrease from baseline anti-FXaor contact the FDA by visiting www.fda.gov/medwatch, or calling life-threatening adverse events, including: anticoagulation dose within 30 days after treatment. Of these 223,activity after administration of ANDEXXA. 1-800-FDA-1088. Arterial and venous thromboembolic events 18 subjects (8%) had a thrombotic event and/or ischemic event afterUse of Heparin Following Administration of ANDEXXAPlease see Brief Summary of full Prescribing Information, resumption. ANDEXXA may interfere with the anticoagulant e ect of heparin. Useincluding Boxed Warning on thromboembolic risks, ischemic risks,of ANDEXXA as an antidote for heparin has not been established. Avoidcardiac arrest, and sudden death, on the following page.Ischemic events, including myocardial infarction andMonitor patients treated with ANDEXXA for signs and symptoms of ischemic stroke arterial and venous thromboembolic events, ischemic events, and cardiacuse of ANDEXXA for the reversal of direct FXa inhibitors (apixaban Reference: 1. Andexxa [prescribing information].Cardiac arrestarrest. To reduce thromboembolic risk, resume anticoagulant therapy asand rivaroxaban) prior to heparinization as ANDEXXA may causeSouth San Francisco, CA: Portola Pharmaceuticals, Inc.; 2020. Sudden deaths soon as medically appropriate following treatment with ANDEXXA.unresponsiveness to heparin. If anticoagulation is needed, use anFor further information, please visitThe safety of ANDEXXA has not been evaluated in patients whoalternative anticoagulant to heparin.Monitor for thromboembolic events and initiate anticoagulationexperienced thromboembolic events or disseminated intravascularADVERSE REACTIONS ANDEXXA.comwhen medically appropriate. Monitor for symptoms and signscoagulation within two weeks prior to the life-threatening bleeding eventThe most common adverse reactions ( 5%) in bleeding patients that precede cardiac arrest and provide treatment as needed.requiring treatment with ANDEXXA. Safety of ANDEXXA also has not beenreceiving ANDEXXA were urinary tract infections and pneumonia.Andexxa and Alexion are registered trademarks ofCoagulation Factor Xaevaluated in patients who received prothrombin complex concentrates,Alexion Pharmaceuticals, Inc.Other brands noted(Recombinant), Inactivatedzhzorecombinant factor VIIa, or whole blood products within seven days priorThe most common adverse reactions ( 3%) in healthy subjects treatedherein are the property of their respective owners.with ANDEXXA were infusion-related reactions. Copyright2020, Alexion Pharmaceuticals, Inc. MINUTES MATTERto the bleeding event. All rights reserved.US/POR-ADX/008209/20FS:6.875" FS:6.875"F:7.875" F:7.875"11439040_Andexxa_Jrnl_Ad_Spread_US_MEDICINE_M1.indd 1 PREPARED BY 11/20/20 11:39 AM11439040 Andexxa Journal Ad Spread US MEDICINE M1Job info Images FontsSpecial InstructionsDate: 11-20-2020 11:39 AM NY_PORT_A057381_4C.tif (CMYK; 351 ppi,Galano Grotesque (Medium, Bold), Muller (Ex- Webcargo or email PDF/X1-a to: production@Client: Portola 352 ppi; 85.43%, 85.17%; 81.4MB), NowCov- traBold, Regular), Muller Narrow (Medium, Bold,usmedicine.comProduct: Andexxa ered_bleed_r1.ai (54.22%; 1.1MB), AndexXa_ Regular, Regular Italic, Bold Italic), Minion Pro Client Code: US/POR-ADX/0082 logo_Gradient_FINAL_centered_10.22.18. (Regular), Galano Grotesque Alt (Medium Italic) Additional InformationWF Issue # 7779444 ai (18.92%; 923KB), RapidSpecificReversal.aiPUB: US MedicineReleasing as: PDFx1A (25.9%; 1.3MB)Final Size: 15.75 X 10.75Finishing: NoneGutter: .5" Inks Additional Comments for SizingColors: 4CPCyan, Magenta, Yellow, Black PI Page Dimensions - Trim7.875 x 10.75"TeamProducer: Sarah_PotterAD: STUDIO-EXPRESSAE: Melissa Hernandez Scale: 1"= 1"QC: None Bleed 16" w x 11" h16" w x 11" hProduction: Frank Robinson Trim/Flat 15.75" w x 10.75" h15.75" w x 10.75" hDigital Artist: YIP (NYC-FCB) Live/Safety 14.75" w x 9.75" h14.75" w x 9.75" h FR Spellcheck:NonePath: PrePress:Portola:Andexxa:11439040:11439040_Andexxa_Jrnl_Ad_Spread_US_MEDICINE_M1.inddPDFX1A _'