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Anthos Therapeutics halts their phase 2 AZALEA-TIMI 71 trial due to significant reduction in bleeding events with abelacimab, making it a potential breakthrough in anticoagulation therapy for atrial fibrillation.
Anthos Therapeutics has announced the discontinuation of their phase 2 AZALEA-TIMI 71 trial due to an “overwhelming reduction” in the study’s composite endpoint of major and clinically relevant non-major bleeding events among patients receiving abelacimab.
Announced on September 18, 2023, the decision to discontinue to the trial comes after a recommendation from the trial’s Data Monitoring Committee concluding abelacimab contributed to a significant reduction in the composite endpoint, which would make abelacimab the first and only factor XI inhibitor to demonstrate a reduction in major bleeding relative to a direct oral anticoagulant (DOAC).1
“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,” said Marc S. Sabatine, MD, MPH, the Lewis Dexter, MD, Distinguished Chair in Cardiovascular Medicine at Brigham and Women’s Hospital and chairman of the Thrombolysis in Myocardial Infarction (TIMI) Study Group.1
According to the release from Anthos Therapeutics, results of the AZALEA-TIMI 71 trial will be published at an upcoming scientific congress.1 In a previous phase 2 trial published in the New England Journal of Medicine in 2021, a single dose of abelacimab proceeding knee surgery was associated with an 80% reduction in venous thromboembolism in the 10 days following surgery relative to use of enoxaparin.2
The phase 2b AZALEA-TIMI 71 trial was designed as event-driven, randomized, active-controlled, blinded endpoint, parallel-group study and launched in 2021 with the intent of assessing the effect of 2 doses of abelacimab relative to open-label rivaroxaban in patients with atrial fibrillation considered to be at moderate to high risk of stroke. For inclusion in the study, patients needed to be at least 55 years of age or older, have a history of atrial fibrillation or atrial flutter with planned indefinite anticoagulation, and an elevated CHA2DS2-VASc score.1
Billed as the largest and longest head-to-head study comparing a factor XI inhibitor to a DOAC, the trial recruited patients from 95 study centers in the US, Canada, Europe and Asia and enrolled a total of 1287 patients. Trial participants were randomized in a 1:1:1 ratio to abelacimab 150 mg once monthly, abelacimab 90 mg once monthly, or rivaroxaban 20 mg daily.1
The trial’s primary outcome of interest was time to first event of composite of International Society on Thrombosis and Haemostasis (ISTH)-defined major bleeding or clinically relevant non-major bleeding. The trial’s secondary outcomes of interest were time to first event ISTH-defined major bleeding events and time to first event ISTH-defined major or minor bleeding events.1
“Given AZALEA-TIMI 71’s overwhelming reduction in bleeding, together with an 80% reduction in thrombosis demonstrated in our earlier VTE study, 1 abelacimab embodies its promise as a hemostasis-sparing anticoagulant and represents a paradigm shift in the prevention of stroke and other thrombotic conditions,” said Dan Bloomfield, MD, Chief Medical Officer of Anthos Therapeutics.1 “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.”
In their release, Anthos Therapeutics pointed out it had initiated an extension study to enable patients to transition from rivaroxaban to abelacimab to benefit from the improved bleeding profile. The company also called attention to the ongoing phase 3 trial of abelacimab called the LILAC-TIMI 76 trial, which is an event-driven, randomized, placebo-controlled, double-blind, parallel-group study. Conducted in a population of patients with atrial fibrillation who have been deemed to be unsuitable for currently available anticoagulation therapy, the trial will compare abelacimab 150 mg against placebo for rate of ischemic or systemic embolism among approximately 1900 patients.1