Adding anticoagulants to antiplatelet therapy after stroke has always meant trading clots for bleeds, but that’s changing thanks to Bayer’s asundexian (Sunharbo), which just became the first-ever FDA-approved Factor XIa inhibitor for secondary stroke prevention.
- Noncardioembolic ischemic strokes are the most common and occur when a clot forms outside the heart and blocks blood flow to the brain.
- Up to 20% of patients who survive their first noncardioembolic ischemic stroke have another stroke within five years, even with GDMT.
- Enter asundexian, which inhibits the enzyme Factor XIa and ultimately reduces thrombosis (bad clotting) while allowing hemostasis to continue (good clotting).
Asundexian’s road to approval wasn’t smooth. Bayer’s first Phase 3 trial, OCEANIC-AF stopped early in November 2023 because asundexian wasn’t more effective than apixaban for stroke prevention.
- However, data analysis suggested that major bleeding was lower with asundexian.
- Thus, the study’s monitoring committee told Bayer to keep OCEANIC-STROKE running.
That bet paid off when the study hit NEJM this April. OCEANIC-STROKE randomized 12.3k patients within 72 hours of stroke or transient ischemic attack to either asundexian 50mg daily or placebo, on top of single or dual antiplatelet therapy. They were then followed for 19 months on average, finding that…
- Ischemic stroke fell to 6.2% vs. 8.4% (HR: 0.74).
- That’s a 26% relative and 2.2% absolute reduction in stroke rate.
- Major bleeding was also statistically similar (1.9% vs. 1.7%) while total disabling or fatal strokes dropped (2.1% vs. 3.0%).
While the approval is exciting, asundexian’s current label has real limitations.
- The approval is for preventing a stroke after a patient has already survived one rather than its original target of preventing first time stroke in AFib patients.
- It still comes with increased risk of GI bleeding (2.7 vs. 2.1 per 100 patient-years).
- At a $748.50 list price per month, costs are likely to limit its adoption.
For now, Bayer will enjoy first mover status since its rivals Novartis (abelacimab) and BMS/J&J (milvexian) have yet to report their own late-stage stroke prevention data.
The Takeaway
OCEANIC-STROKE and Asundexian’s recent approval suggest that Factor XIa inhibition has its benefits, just not everywhere. As with every approval, the work is just starting for asundexian since Bayer must now convince the medical community that those benefits justify its price.
