Bayer is stopping a pivotal clinical trial for its experimental treatment for atrial fibrillation at the recommendation of an independent committee that concluded the drug would not be more effective than a Bristol Myers Squibb and Pfizer product widely used to treat the heart condition.
The Bayer drug, asundexian, was being evaluated in a Phase 3 study enrolling patients with atrial fibrillation who are at risk of stroke. The once-daily drug is an oral small molecule designed to block Factor XIa, a protein in the coagulation cascade. The irregular heartbeat caused by afib leads to poor blood flow that raises the risk of blood clots or stroke. Drugs available to treat the condition also causes bleeding. By targeting Factor Xia, Bayer hoped its drug would prevent stroke without also leading to the bleeding complications of currently used therapies.
The Phase 3 study, OCEANIC-AF, compared asundexian to Eliquis, a blood-thinning drug from BMS and Pfizer that works by blocking a different clotting protein called FXa. Bayer said its drug’s safety was consistent with earlier tests but it provided no specific details about the lack of efficacy conclusion reached by the independent data monitoring committee. The company did say that the committee recommends continuing OCEANIC-STROKE, a separate placebo-controlled Phase 3 test of the drug for the prevention of ischemic stroke.
“Although the results from this analysis do not support the continuation of the OCEANIC-AF study, we will continue investigating asundexian in the OCEANIC-STROKE study and are currently reevaluating other indications in patients in need of antithrombotic treatment,” Christian Rommel, member of the executive committee of Bayer’s Pharmaceutical Division and global head of research and development, said in a prepared statement.
The bleeding risks associated with currently available afib therapies have led companies to try to develop safer alternatives. BMS is among them, having reached Phase 3 testing with its Factor X1a inhibitor, milvexian. In a note sent to investors Monday, William Blair analyst Matt Phipps wrote that the failure of Bayer’s drug will affect investor confidence in the ability of Factor XIa inhibitors to top Eliquis in atrial fibrillation. Milvexian is expected to post Phase 3 results in 2027.
Privately held Anthos Therapeutics reached Phase 2 testing with its Factor XI inhibitor, an antibody called abelacimab. During the American Heart Association’s meeting earlier this month, the company reported the early stoppage of that drug’s mid-stage study—a move prompted by greater than expected efficacy. Anthose said its drug led to a 67% lower risk of bleeding compared to Johnson & Johnson Factor Xa inhibitor, Xarelto.
Phipps said comparisons across the trials are difficult without any standardized assays, but he noted that Anthos reported a sustained 99% reduction of Factor XIa compared to roughly 90% inhibition of Factor XIa activity for Bayer’s asundexian at trough levels in the blood. That indicates it’s possible Bayer’s drug was underdosed in its trials, particularly as monotherapy, Phipps said. By contrast, BMS has tested a wider range of doses, including once-daily and twice-daily dosing. BMS is testing a 100 mg dose of milvexian twice daily as a monotherapy in atrial fibrillation, but a 25 mg twice-daily dose on top of platelet inhibitors in secondary stroke prevention or acute coronary syndrome patients, Phipps said.
Bayer said it will further analyze the Phase 3 data for its drug to better understand what happened in the afib study. The company also plans to publish the data.
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