Abelacimab: A Comprehensive Monograph on a Novel Factor XI Inhibitor Poised to Redefine Anticoagulation Safety

Executive Summary

Abelacimab (DrugBank ID: DB16682; CAS: 2098724-83-3) is an investigational, fully human monoclonal antibody representing a potential first-in-class anticoagulant therapy.[1] Its development is predicated on a novel therapeutic hypothesis: achieving "hemostasis-sparing anticoagulation" by selectively targeting the intrinsic coagulation pathway.[4] This is accomplished through a unique dual-inhibition mechanism, targeting both the zymogen Factor XI (FXI) and its activated form, Factor XIa, thereby aiming to uncouple pathological thrombosis from physiological hemostasis—a critical limitation of all currently available anticoagulants.[6]

The clinical development program for abelacimab has been highlighted by the landmark Phase 2b AZALEA-TIMI 71 trial. In this study, abelacimab demonstrated an unprecedented and statistically profound reduction in bleeding events compared to the standard-of-care direct oral anticoagulant (DOAC), rivaroxaban, in patients with atrial fibrillation (AF) at moderate-to-high risk of stroke.[8] This striking safety signal, which led to the trial's early termination, has positioned abelacimab as a leading candidate in a new generation of safer antithrombotic agents.

Building on this foundation, abelacimab is being advanced through a robust and strategically designed Phase 3 program. This program targets patient populations with high unmet medical needs, including AF patients deemed unsuitable for current anticoagulants (LILAC-TIMI 76 trial) and patients with Cancer-Associated Thrombosis (CAT), a setting complicated by high bleeding risk (ASTER and MAGNOLIA trials).[11] The U.S. Food and Drug Administration (FDA) has recognized this potential by granting two separate Fast Track Designations for the CAT and AF indications.[14]