By Tristan Manalac

Pictured: Illustration of a blood clot in a blood vessel/iStock, libre de droit

Anthos Therapeutics is ending the Phase II AZALEA-TIMI 71 study ahead of schedule after its investigational monoclonal antibody abelacimab demonstrated an “overwhelming reduction” in bleeding compared to Bayer and Johnson & Johnson’s Xarelto (rivaroxaban), the company announced Monday.
Patients treated with abelacimab saw a sharp reduction in the composite endpoint of major and clinically relevant non-major bleeding events compared with counterparts given rivaroxaban, the current standard-of-care oral anticoagulant.
The Massachusetts-based biopharma did not provide specific data in Monday’s announcement but said that the Data Monitoring Committee stopped the study early following these data. Anthos will share the full results and analysis of the trial in an upcoming medical meeting.
Due to the “overwhelming reduction in bleeding” reported in AZALEA-TIMI 71, abelacimab may represent a “paradigm shift” in atrial fibrillation care particularly in the prevention of stroke and other thrombotic conditions, Anthos CMO Dan Bloomfield said in a statement.
Abelacimab is a highly selective and fully human monoclonal antibody that works by inhibiting both Factor XI and its active form Factor XIa. Both proteins play an important role in the coagulation cascade, and high concentrations have been known to promote thrombosis, or pathological clots that impede the flow of blood in veins and arteries.
The investigational antibody was first developed by Novartis, which licensed it to Anthos at the time of the biotech’s launch in February 2019. Anthos was founded by the private investment firm Blackstone Life Sciences, which provided $250 million in initial support.
In a previous study, published August 2021 in The New England Journal of Medicine, abelacimab was able to reduce venous thromboembolism by approximately 80% versus standard of care in patients undergoing knee arthroplasty. The proof-of-concept study gave abelacimab at 30-mg, 75-mg and 150-mg doses, and found that serious adverse events were uncommon across all three dose levels.
Anthos has also demonstrated that at its 150-mg dose, abelacimab can maintain around 98% inhibition of its target proteins over the dosing interval.
“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,” Bloomfield said in Monday’s press release.
Anthos has started an extension study to AZALEA-TIMI 71, which will allow participants allocated rivaroxaban to switch to abelacimab. The company is also evaluating the investigational antibody in cancer-associated thrombosis, for which it has two Phase III trials called ASTER and MAGNOLIA. In January 2023, the company kicked off its Phase III trial of abelacimab in high-risk atrial fibrillation patients who cannot receive current anticoagulant treatments.