Abelacimab, a dual-acting factor XI/XIa inhibitor, demonstrated a significant reduction in bleeding in a head-to-head study comparing a factor XI inhibitor to a direct oral anticoagulant (DOAC), according to Anthos Therapeutics Inc, a clinical-stage company developing innovative therapies for cardiovascular diseases.
The AZALEA-TIMI 71 phase 2 study in 1,287 patients with atrial fibrillation at moderate-to-high risk of stroke met its primary endpoint. The study was stopped early by the Data Monitoring Committee due to an overwhelming reduction in the composite of major and clinically relevant non-major bleeding in patients taking abelacimab compared with patients taking rivaroxaban, a leading standard-of-care DOAC.
“The AZALEA-TIMI 71 study is the largest and longest head-to-head study of a factor XI inhibitor to provide definitive evidence of a highly significant reduction in bleeding as compared to the standard-of-care anticoagulant. With a median of 21 months of follow-up, spanning more than 2,000 patient-years, AZALEA-TIMI 71 represents a landmark study confirming the promise of factor XI inhibition as causing substantially less bleeding than a current standard-of-care,” says Marc S Sabatine, MD, MPH, the Lewis Dexter, MD, Distinguished Chair in Cardiovascular Medicine at Brigham and Women’s Hospital, professor at Harvard Medical School, and chairman of the Thrombolysis in Myocardial Infarction Study Group, in a release.
Abelacimab is a novel, highly selective, fully human monoclonal antibody with dual inhibitory activity against factor XI and its active form, factor XIa. Abelacimab 150 mg maintains approximately 98% inhibition over the dosing interval, recapitulating the benign bleeding profile of patients with genetic factor XI deficiency.
Prior to AZALEA-TIMI 71, abelacimab achieved an approximate 80% reduction in venous thromboembolism (VTE) versus a standard-of-care comparator in a gold standard proof-of-concept efficacy study that was published in the New England Journal of Medicine.
“Given AZALEA-TIMI 71’s overwhelming reduction in bleeding, together with an 80% reduction in thrombosis demonstrated in our earlier VTE study, abelacimab embodies its promise as a hemostasis-sparing anticoagulant and represents a paradigm shift in the prevention of stroke and other thrombotic conditions,” says Dan Bloomfield, MD, chief medical officer of Anthos Therapeutics, in a release. “If approved, more patients with atrial fibrillation could be treated effectively and safely, with a much lower risk of bleeding with abelacimab as compared to a DOAC.”
Around 40% to 60% of patients with atrial fibrillation are not prescribed anticoagulants today. This underuse of anticoagulants for stroke prevention has been cited as one of the greatest public health issues facing cardiovascular patients. In a physician survey, the foremost barrier to patients taking oral anticoagulants was bleed-related.
“Abelacimab has the potential to provide a game-changing treatment option for all those patients who live with the daily fear of bleeding while taking current anticoagulants. We can now imagine a future where these patients are able to resume and enjoy activities that they are currently being forced to give up due to concerns associated with bleeding,” says Leslie Lake, president of the National Blood Clot Alliance, in a release. “We are thrilled that AZALEA-TIMI 71 has demonstrated such a positive outcome and excited about the promise that it offers to patients.”
Anthos Therapeutics has initiated an extension study to enable patients to transition from rivaroxaban to abelacimab to benefit from the improved bleeding profile. Further, a Fast-Track Designation for abelacimab was previously granted by the US Food and Drug Administration for the prevention of stroke and systemic embolism in patients with atrial fibrillation.
Subsequently, primary data from the AZALEA-TIMI 71 study of patients with atrial fibrillation at moderate-to-high risk of stroke was selected for a late-breaking session at the American Heart Association Scientific Sessions 2023, being held Nov 11-13 in Philadelphia, Penn.
Late-breaking presentation details are as follows:
- Oral Presentation: Abelacimab, a novel factor XI/XIa inhibitor, vs rivaroxaban in patients with atrial fibrillation: primary results of the AZALEA-TIMI 71 randomized trial
- Session Title: LBS.05 – Late-Breaking Science: Shocking Decisions in AFib Care
- Date: Sunday, Nov 12
- Session Time: 8am – 9:15am ET
- Presentation Time: 8:15am – 8:25am ET
- Location: Pennsylvania Convention Center; Philadelphia, Penn