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Bentracimab Overview
Bentracimab Overview

The reversal agent being studied, previously known as PB2452, is now called bentracimab.  Bentracimab is a novel, recombinant, human monoclonal antibody antigen-binding fragment designed to reverse the antiplatelet activity of ticagrelor in major bleeding and urgent surgery situations. In a Phase 1 clinical trial, bentracimab demonstrated the potential to bring life-saving therapeutic benefit through immediate and sustained reversal of  the antiplatelet activity of ticagrelor, mitigating concerns regarding bleeding risks associated with the use of antiplatelet drugs. The results of the Phase 1 clinical trial of PB2452 in healthy volunteers were published in the New England Journal of Medicine in March 2019. 

Bentracimab has a dual mechanism of action in that it binds both to ticagrelor and its major active metabolite (Ticagrelor Active Metabolite, or TAM), allowing restoration of platelet aggregation. It binds with strong affinity, approximately 100-fold greater than ticagrelor to its P2Y12 receptor. It has shown no affinity for other innate or pharmacologic targets.  Bentracimab continues to bind ticagrelor as it dissociates from the P2Y12 receptor or plasma proteins. Ticagrelor is primarily eliminated through the gastrointestinal tract. However, the complex of ticagrelor or TAM and bentracimab is eliminated primarily by the renal route. 

In April 2019, PB2452 received Breakthrough Therapy designation from the FDA. Breakthrough Therapy designation may be granted by FDA when preliminary clinical evidence indicates that the drug may demonstrate substantial improvement over existing therapy. There currently is no alternative reversal therapy for the antiplatelet effects of ticagrelor or any other antiplatelet drugs.  Similarly, in February 2020, the European Medicines Agency granted bentracimab PRIME Designation.