Clinical Overview: Asundexian for Secondary Prevention in Patients With Non-Cardioembolic Ischemic Stroke

Asundexian was granted FDA Fast Track Designation based on a phase 2 study evaluating its safety and efficacy combined with antiplatelet therapy in patients following an acute, non-cardioembolic ischemic stroke.

Asundexian (BAY2433334) is an investigational, orally administered coagulation factor XIa (FXIa) inhibitor. In contrast to available anticoagulants, research shows that FXIa inhibitors, through selective inhibition of the intrinsic coagulation cascade, can reduce the occurrence of thrombosis without increasing bleeding risk.1-3

In February 2022, Bayer announced that the FDA granted asundexian Fast Track Designation based on the preliminary findings of PACIFIC-STROKE (NCT04304508), a phase 2 study evaluating asundexian’s safety and efficacy when combined with antiplatelet therapy in patients following an acute, non-cardioembolic ischemic stroke.4

A 3-part study of more than 4000 patients world-wide, the PACIFIC (Phase 2 Program of Anticoagulation via Inhibition of FXIa by the Oral Compound BAY2433334) program is also exploring the role of asundexian (vs apixaban) in stroke prevention in patients with non-valvular atrial fibrillation (PACIFIC-AF, NCT04218266) and as secondary prevention (vs placebo) in combination with antiplatelet therapy following acute myocardial infarction (MI) (PACIFIC-AMI, NCT044303434).2,5

A phase 1 study (NCT04510987) to evaluate asundexian’s pharmacokinetics, pharmacodynamics, and safety in subjects with varying degrees of renal compromise (including dialysis-dependence) is ongoing.6

Mechanism of Action

Asundexian is a chemically synthesized, small molecule that binds to and inhibits the activity of the active, catalytic site of FXIa. Through selective inhibition of the intrinsic coagulation pathway, asundexian may prevent pathological clot formation (thrombosis) without hindering hemostasis (clotting that occurs in response to injury).1,6

Dosage and Administration

For the secondary prevention of non-cardioembolic stroke or MI, phase 2 PACIFIC program participants receive investigational doses of 10 mg, 20 mg, or 50 mg.2 For the prevention of stroke in non-valvular atrial fibrillation, phase 2 PACIFIC program participants receive investigational doses of 20 mg or 50 mg.2

A phase 1 dose-escalation and food interaction study has shown asundexian may be taken without regard to meals. Of note, asundexian does not appear to have any clinically meaningful effect on CYP3A4 activity.7

Adverse Events (AEs)

Asundexian has been well tolerated in phase 1 studies. In a phase 1 dose-escalation and food interaction study, researchers screened 86 healthy men for treatment-emergent AEs (TEAEs), including treatment-related bleeding, hepatobiliary dysfunction, and pancreatic disorders.

The reported TEAEs attributed to the study drug in 8.6% of 70 subjects in the dose escalation study included dysgeusia (n=4), nausea (n=1) and ventricular ectopic beats (n=1). In the food-interaction portion of the study (n=16), 2 subjects experienced a TEAE attributed to asundexian.

The first subject reported palpitations, vertigo, and sensation of a foreign body. The second subject reported paresthesia, xerostomia, and feeling cold. No clinically significant electrocardiogram, physical examination, or laboratory findings were observed in any subject.1

In a separate phase 1 dose-escalation study of 48 healthy men, headache was the most common TEAE, followed by nasopharyngitis. All events were considered mild and no clinically significant electrocardiogram, physical examination, or laboratory findings were observed in any subject.7

Warnings and Precautions

Asundexian appears to be well tolerated based on phase 1 studies, however these studies were performed using small groups of healthy subjects.1,7 Results of larger phase 2 studies are yet to be reported and phase 3 studies have not yet begun.

Pregnancy and Lactation

Asundexian has not been studied in pregnant women. It is unknown whether the drug is passed into breast milk.

About the Author

Allison T. Rhoads, PharmD, is a clinical pharmacist at an outpatient oncology center in Tallahassee, Florida.


  1. Thomas D, Kanefendt F, Schwers S, Unger S, Yassen A, Boxnick S. First evaluation of the safety, pharmacokinetics, and pharmacodynamics of BAY 243334, a small molecule targeting coagulation factor XIa. J. Thromb. Haemost. 2021;19(10):2407-2416. doi:10.1111/jth.15439
  2. Fredenburgh JC, Weitz JI. New anticoagulants: Moving beyond the direct oral anticoagulants. J. Thromb. Haemost. 2021;19(1):20-29. doi:10.1111/jth.15126
  3. J. Kakkar A, Weitz J, Büller H, Connors J. Factor XI inhibition: The holy grail of haemostasis-sparing anticoagulation. Presented at: International Society on Thrombosis and Haemostasis (ISTH) Virtual Congress 2021. July 20, 2021. Accessed March 9, 2022.
  4. Multicenter, randomized, placebo-controlled, double-blind, parallel group, dose-finding phase 2 study to evaluate efficacy and safety of BAY2433334 in patients following an acute non-cardioembolic ischemic stroke. identifier: NCT04304508. Updated February 9, 2022. Accessed March 9, 2022.
  5. Bayer Receives U.S. FDA Fast Track Designation for asundexian Stroke Program. News release. Bayer Communications. February 10, 2022. Accessed March 9, 2022.
  6. Investigation of pharmacokinetics, pharmacodynamics, safety, and tolerability of a single oral dose of 25 mg BAY 2433334 in male and female participants with different stages of renal impairment (including on dialysis), as compared to age, gender and weight matched participants in a single-center, non-randomized, non-controlled, non-blinded, group stratification design study. identifier: NCT04510987. Updated December 22, 2021. Accessed March 10, 2022.
  7. Kubitza D, Heckmann M, Distler J, Koechel A, Schwers S, Kanefendt F. Pharmacokinetics, pharmacodynamics and safety of BAY 2433334, a novel activated factor XI inhibitor, in healthy volunteers: A randomized phase 1 multiple-dose study. Br J Clin Pharmacol. Published online January 10, 2022. doi:10.1111/bcp.15230
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