FDA Grants Fast Track Designation for Atrial Fibrillation Therapy Asundexian

In a recent announcement, the FDA granted fast track designation for Bayer’s investigational drug asundexian (BAY2433334), an oral direct, potent inhibitor of activated coagulation factor XI (FXIa), as a potential treatment to prevent stroke and systemic embolism in patients with atrial fibrillation (AF).¹

The therapy is currently being evaluated in the OCEANIC clinical trial program, which comprises 2 large multinational studies, OCEANIC-AF (NCT05643573) and OCEANIC-STROKE (NCT05686070), expected to enroll more than 27,000 patients over more than 40 countries. This was the second time asundexian receives fast track designation, the first of which came in 2022 for the prevention of stroke in patients after a non-cardioembolic ischemic stroke.

"The second Fast Track Designation for asundexian emphasizes the medical need to prevent stroke and systemic embolism in people diagnosed with atrial fibrillation,” Christian Rommel, member, Executive Committee, AG Pharmaceutical Division, and head, Research and Development, Bayer, said in a statement.¹ “This designation provides an opportunity to accelerate the development of asundexian and quickly address current patient needs."

FXIa inhibitors have become an emerging class of medicines, viewed as potentially safer and more effective alternatives to new oral anticoagulants. Asundexian acts selectively on the coagulation cascade, thereby offering the potential to prevent events like stroke without a corresponding increase in bleeding risk. Inhibiting FXI reduces the formulation of pathologic thrombi while preserving the ability to form clots in response to bleeding, which constrasts the mechanism of action of currently used NOACs like apixaban (Eliquis) and rivaroxaban (Xarelto).

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OCEANIC-AF, a parallel-group, comparator-controlled, phase 3 study, is expected to include 18,000 participants who will be assigned to 1 of 2 groups. Dependent on the treatment group, participants will either take asundexian orally once a day or apixaban twice a day for approximately 9-33 months. Site visits will occur every 3 to 6 months, which includes blood sampling, physical examinations, vital sign testing, and other measures. Participants will be asked about their quality of life, how they are feeling, and what adverse events they’ve experienced.²

Some of the primary outcome measures of the study include time to first occurrence of stroke or systemic embolism, and time to first occurrence of major bleeding, based on International Society on Thrombosis and Hemostasis (ISTH) criteria. Patients must be at least 18 years of age, have documented AF by ECG evidence, and have CHA2DS2-VASc score of greater than 3 for males or 4 for females. Those with mechanical heart valve prosthesis, moderate-to-severe mitral stenosis, AF only due to reversible cause, and a requirement for chronic anticoagulation for a different indication than AF were excluded from the study.

OCEANIC-STROKE, the second phase 3 trial of the program, randomly assigned 9300 patients to either asundexian or placebo as tablets once a day for at least 3 months up to 31 months. Every 3 months during the treatment, either a phone call or a site visit is scheduled on an alternating basis. Similar to OCEANIC-AF, the primary outcome measures of this trial include time to first occurrence of ischemic stroke or ISTH major bleeding. The trial features patients aged at least 18 years of age with acute non-cardioembolic stroke or high-risk transient ischemic attack with systemic or cerebrovascular atherosclerosis or acute non-lacunar infarct.³

Rommel added, “Despite significant advances in treatment, potential concerns of bleeding risks remain at the forefront of thrombosis management. Asundexian is currently investigated as a candidate in an entirely new class of antithrombotic treatment options aiming to selectively modulate coagulation, address patients with concerns of bleeding, and focus on indications where current anticoagulation is not used."¹

REFERENCES
1. Bayer receives US FDA fast track designation for asundexian atrial fibrillation program. News release. May 16, 2023. Accessed May 19, 2023. https://www.businesswire.com/news/home/20230516005400/en/Bayer-Receives-U.S.-FDA-Fast-Track-Designation-for-asundexian-Atrial-Fibrillation-Program
2. A study to learn how well the study treatment asundexian works and how safe it is compared to apixaban to prevent stroke or systemic embolism in people with irregular and often rapid heartbeat (Atrial fibrillation), and at risk for stroke (OCEANIC-AF). Clinicaltrials.gov. Accessed May 19, 2023. https://clinicaltrials.gov/ct2/show/NCT05643573?term=OCEANIC+AF&draw=2&rank=1
3. A study to learn more about asundexian (also called BAY2433334) for prevention of ischemic stroke in male and female participants aged 18 years and older who already had such a stroke due to a blood clot that formed outside the heart and traveled to the brain, or temporary stroke-like symptoms (OCEANIC-STROKE). Clinicaltrials.gov. Accessed May 19, 2023. https://clinicaltrials.gov/ct2/show/NCT05686070?term=OCEANIC+STROKE&draw=2&rank=1