AndexXa (coagulation factor Xa (recombinant), inactivated -zhzo) / Daiichi Sankyo, AstraZeneca - LARVOL DELTA

A Study to Investigate Andexanet Dosing and the Interaction Between Andexanet and Subsequent Enoxaparin in Healthy Participants (clinicaltrials.gov) - P1 | N=186 | Recruiting | Sponsor: AstraZeneca | Not yet recruiting ➔ Recruiting

Enrollment open

Timely Door-To-Reversal in Anticoagulation-Associated Intracranial Hemorrhage: Rate limiting steps and predictors in a Multicenter Observational Study. (ISC 2026) - "Overall, 81% were on FXa inhibitors and 19% on warfarin. Reversal agents included andexanet alpha (43%) and prothrombin complex concentrates (56%)... Similar to the acute ischemic stroke treatment timeline, reversal of anticoagulation in AA-ICrH was significantly faster when using a SA protocol, underscoring the critical role of streamlined emergency pathways using SA to improve DTR times. These observations highlight the need for targeted interventions to reduce delays and leverage the rapid onset of action of the approved reversal agents."

Clinical • Observational data • Cardiovascular • Cerebral Hemorrhage • CNS Disorders • Hematological Disorders • Ischemic stroke

Andexanet Alfa versus 4F-PCC for Direct Anticoagulation Reversal in Intracranial Hemorrhage: A Quality Improvement Analysis (ISC 2026) - "In this real-world analysis, andexanet alfa was linked to a higher risk of significant intracranial hemorrhage growth than 4F-PCC, despite similar rates of neurological deterioration, thromboembolic events, functional disability, and mortality. 4F-PCC may serve as a clinically viable alternative for reversing FXa inhibitor anticoagulation in intracranial hemorrhage."

Atrial Fibrillation • Cardiovascular • Cerebral Hemorrhage • CNS Disorders • Hematological Disorders • Venous Thromboembolism

CTA Spot Sign and Response to Andexanet in FXai-associated Intracerebral Hemorrhage: a Secondary Analysis of ANNEXa-I (ISC 2026) - "The presence of the spot sign and its features were significantly associated with HE in FXai-associated ICH. The treatment effect of andexanet was still consistent regardless of the presence of the spot sign and its features"

Cerebral Hemorrhage • Hematological Disorders

Early administration of andexanet alfa reduces hematoma expansion in factor Xa inhibitor-associated intracerebral hemorrhage (ISC 2026) - "This association tended to be consistent regardless of OTD time but was more pronounced in the patients with a shorter OTD time (Figure). The rate of favorable outcome was numerically higher in the andexanet alfa group but did not differ significantly between the two groups (53% vs 38%, adjusted odds ratio 2.45; 95%CI 0.89-6.72).Conclusions : Early administration of andexanet alfa inhibits hematoma expansion and might contribute to improved functional outcome in intracerebral hemorrhage patients associated with factor Xa inhibitors."

Cerebral Hemorrhage • Hematological Disorders

Combined Antithrombin and Heparin Supplementation to Blood for Restoring Heparin Responsiveness After Andexanet Alfa Exposure: An In Vitro Model. (PubMed, EJHaem) - "High-dose AT with heparin mitigates andexanet-induced heparin resistance in vitro, though residual TG and clot formation suggest ongoing thrombotic risk, warranting further study. The authors have confirmed clinical trial registration is not needed for this submission."

Journal • Preclinical

First use of andexanet alfa in the management of massive delayed hemothorax. (PubMed, Turk J Emerg Med) - "The patient had been on long-term rivaroxaban, a direct oral anticoagulant, due to underlying comorbid conditions. After follow-up, the patient remained in good condition. This case demonstrates that andexanet alfa can be an effective reversal agent in life-threatening cases of massive delayed hemothorax."

Journal • Respiratory Diseases

Prothrombin Complex Concentrate for Reversal of Factor Xa Inhibitor-Associated Acute Major Gastrointestinal Bleeding. (PubMed, Am J Med) - "Prothrombin complex concentrate achieved 73% hemostatic efficacy in factor Xa inhibitor-associated gastrointestinal bleeding, with low thromboembolic rates and mortality similar to published data, supporting current guideline recommendations for reversal."

Journal • Cardiovascular • Gastroenterology

Comparison of activated and 4-factor prothrombin complex concentrates for reversal of apixaban- and rivaroxaban-associated major bleeding. (PubMed, J Thromb Thrombolysis) - "Factor Xa inhibitor (FXaI)-associated major bleeding presents a critical management challenge. In FXaI-associated major bleeding, aPCC and 4 F-PCC achieved comparable hemostatic outcomes with low thromboembolic event rates. These results support either agent as a reasonable reversal option when andexanet alfa is unavailable, with aPCC potentially effective at lower doses."

Journal • Cardiovascular • Cerebral Hemorrhage • CNS Disorders • Hematological Disorders • Thrombosis

In brief: Andexanet alfa (Andexxa) withdrawn. (PubMed, Med Lett Drugs Ther) - No abstract available

Journal

Balancing Bleeding and Thrombosis in Dental Management of Patients on Novel Oral Anticoagulants: A Narrative Evidence Synthesis. (PubMed, Cureus) - "Reversal agents, including idarucizumab for dabigatran and andexanet alfa for apixaban, edoxaban, and rivaroxaban, remain emergency-only tools because of their logistical and prothrombotic constraints. Nonetheless, this narrative review enables safe continuation in most scenarios, minimizing morbidity through pharmacokinetic awareness, local hemostatic rigor, and surgical conservatism. Future prospective registries with standardized outcomes are essential to validate interruption thresholds and adjunctive modalities in this expanding anticoagulation population."

Journal • Review • Cardiovascular • Hematological Disorders • Inflammation • Orthopedics • Thrombosis

A Study to Investigate Andexanet Dosing and the Interaction Between Andexanet and Subsequent Enoxaparin in Healthy Participants (clinicaltrials.gov) - P1 | N=186 | Not yet recruiting | Sponsor: AstraZeneca

New P1 trial

The Andexxa arc: From urgency to uncertainty to unapproval. (PubMed, Am J Health Syst Pharm) - No abstract available

Journal • Cardiovascular • Cerebral Hemorrhage • Hematological Disorders • Thrombosis

Position statement of the Polish Society of Gastroenterology on the use of andexanet alfa in patients with gastrointestinal bleeding taking factor Xa inhibitors. (PubMed, Prz Gastroenterol) - "Andexanet alfa is a recombinant, inactive analogue of human FXa which specifically and effectively reverses the activity of FXa inhibitors, namely rivaroxaban and apixaban. This agent should be used in patients receiving an FXa inhibitor who present with life-threatening or uncontrolled gastrointestinal bleeding, accompanied by hypovolaemia and haemodynamic instability, and who fail to respond to initial fluid resuscitation or experience persistent bleeding despite endoscopic intervention. This article presents the position of the experts of the Polish Society of Gastroenterology regarding the management of patients with gastrointestinal bleeding taking FXa inhibitors and the indications for the use of andexanet alfa."

Journal • Gastroenterology

Use of Andexanet Alfa to Reverse Heparin After Cardiopulmonary Bypass. (PubMed, Ann Thorac Surg Short Rep) - "Andexanet alfa has demonstrated effective in vitro heparin reversal, but clinical use has not been reported. We review the preclinical data on andexanet alfa as a heparin reversal agent and report a clinical case of andexanet alfa infusion, with complete laboratory and clinical evidence of heparin reversal."

Journal

Update on the Safety of Andexxa (FDA) - "Since approval, the U.S. Food and Drug Administration (FDA) has received postmarketing safety data on thromboembolic events...Based on available data, the serious risks including the increase in thromboembolic events are such that the FDA considers the risks of the product to outweigh its benefits. The FDA has communicated this position to AstraZeneca, and the company has submitted a request to voluntarily withdraw the BLA for the product for commercial reasons. Additionally, the company has confirmed that it will end U.S. commercial sales by December 22, 2025. Andexxa will no longer be manufactured for or sold in the U.S. by AstraZeneca after December 22, 2025."

Discontinued • FDA event • Hematological Disorders

Comparative Thrombotic Risk Following Administration of Andexanet Alfa Versus Four-Factor Prothrombin Complex Concentrate in Anticoagulant Reversal of Factor Xa Inhibitors (ASHP 2025) - No abstract available

Reassessing Andexanet Alfa: Evidence, Safety, and Cost Support 4F-PCC Utilization (ASHP 2025) - No abstract available

Clinical

Machine Learning–Based risk stratification in patients with direct anti‑xa Inhibitors–Related bleeding treated with four‑factor prothrombinex complex concentrate (4F-PCC) (ASH 2025) - "Although Andexanet alfa is FDA-approvedfor reversal, its high cost and limited availability restrict its use in many centers... 4F-PCC showed efficacy and safety in the reversal of direct anti-Xa inhibitor related majorbleeding. Machine learning approach successfully identified predictors to classify patients with high andlow risk for mortality outcomes. Further large-scale prospective studies are warranted to validate this riskstratification model and support therapeutic decision-making in patients presenting with major bleeding."

Clinical • Machine learning • Cerebral Hemorrhage • CNS Disorders • Hematological Disorders

Specific reversal agents for direct oral anticoagulants in neurosurgical emergencies - a systematic review. (PubMed, Res Pract Thromb Haemost) - "Idarucizumab and andexanet alfa are approved reversal agents, yet their effectiveness and safety in neurosurgical emergencies remain unclear. The use of DOAC reversal agents in emergency neurosurgery appears feasible and may support surgical hemostasis in selected patients. However, further research is warranted, particularly regarding the off-label use of andexanet, given the limited evidence and potential safety concerns."

Journal • Review • Cardiovascular

A UK-wide analysis of 2265 patients receiving a reversal agent for direct oral anticoagulant-associated bleeding. (PubMed, J Thromb Haemost) - "Reversal agents were generally used in patients with clinical evidence of major bleeding but were administered long after the last anticoagulant dose. In gastrointestinal bleeding, andexanet alfa was associated with a higher thrombotic risk than PCC."

Journal • Cardiovascular • Cerebral Hemorrhage • CNS Disorders • Gastroenterology • Hematological Disorders • Thrombosis

Automated Imaging and Analysis of Platelet, Coagulation and Fibrinolysis Activities Using a Novel Flow Chip-Based System at Physiological Temperature. (PubMed, Micromachines (Basel)) - "In platelet-sensitive mode, MC-2S demonstrated high sensitivity to antiplatelet therapy with aspirin or cangrelor. In coagulation-sensitive mode, it detected the anticoagulant effect of rivaroxaban plus its reversal by andexanet-α. In fibrinolysis-sensitive mode, it monitored tissue-type plasminogen activator-induced thrombus dissolution, inhibited by tranexamic acid. Collectively, the MC-2S platform was found to provide a versatile, physiologically relevant tool for functional hemostasis testing, with high potential for the acute and subacute evaluation of patient blood samples in the context of bleeding disorders, thrombosis risk, and drug monitoring."

Journal • Cardiovascular • Hematological Disorders • Thrombosis

Characteristics of Intracranial Hemorrhage in Patients on Factor-Xa Inhibitors: Japan Stroke Data Bank. (PubMed, Intern Med) - "Results A total of 859 patients (rivaroxaban, n=227; apixaban, n=355; edoxaban, n=277) with ICH (ICH: n=822, age 79±9 years, 38.6% female; SAH: n=37, age 79±10, 75.7% female) were investigated. Conclusion This study presents the clinical outcomes prior to the approval of andexanet alfa. Further studies are needed to evaluate post-approval outcome changes."

Journal • Cardiovascular • Cerebral Hemorrhage • CNS Disorders • Hematological Disorders • Subarachnoid Hemorrhage

Andexanet Alfa in Emergency Cranial Neurosurgical Procedures: A Bicentric Analysis of Efficacy and Safety. (PubMed, Neurocrit Care) - "Our findings suggest that andexanet alfa is highly effective in preventing secondary bleeding during neurosurgery in patients on factor Xa inhibitors. However, the risk for ischemic events must be carefully considered."

Journal • Cardiovascular • Cerebral Hemorrhage • CNS Disorders • Gastrointestinal Disorder • Hematological Disorders • Pulmonary Embolism • Respiratory Diseases

Clinical laboratory testing of blood from patients presenting to the emergency department with acute bleeding due to factor Xa inhibitors: An unmet medical need. (PubMed, Clin Chim Acta) - "For patients on warfarin, stat testing of blood for the prothrombin time and calculation of the International Ratio (PT-INR) are used to determine if acute bleeding is caused by excess anticoagulation. Direct acting oral anticoagulants (DOACs) include those that inhibit Factor Xa (apixaban, rivaroxaban, edoxaban, and betrixaban) or Factor IIa (dabagatran)...However, current laboratory assays for anti-Factor Xa are calibrated for the specific DOAC used and results are not typically available in emergency departments. Therefore, there is a need to produce a rapid bedside blood test that can detect bleeding to any DOAC drug that was prescribed."

Journal • Cardiovascular • Ischemic stroke