Comprehensive Report on Bentracimab (PB2452): A Novel Ticagrelor Reversal Agent

1. Executive Summary

Bentracimab, also known by its development code PB2452, is an intravenous human monoclonal antibody fragment (Fab) engineered for the rapid and specific reversal of the antiplatelet effects of ticagrelor and its active metabolite, AR-C124910XX.[1] This investigational agent addresses a significant unmet medical need for patients treated with ticagrelor who experience uncontrolled major or life-threatening bleeding or require urgent surgery or invasive procedures where normal hemostasis is critical.

The pivotal Phase 3 REVERSE-IT trial (NCT04286438) has provided compelling evidence of Bentracimab's efficacy and safety. Key findings indicate that Bentracimab administration leads to a rapid (within 5-10 minutes) and sustained (over 20-24 hours) reversal of ticagrelor-induced platelet inhibition, as measured by P2Y12 reactivity units (PRU).[1] The trial demonstrated high rates of effective hemostasis in both patients undergoing urgent surgery (100%) and those with major bleeding (83.1%).[3] The safety profile of Bentracimab has been reported as favorable, with no serious allergic reactions or treatment discontinuations attributed to the drug in the REVERSE-IT trial.[4]

Reflecting its potential to address a critical unmet need, Bentracimab has received several expedited regulatory designations from the U.S. Food and Drug Administration (FDA), including Breakthrough Therapy Designation (granted in 2019), Orphan Drug Designation (granted March 18, 2025), and Priority Review for its Biologics License Application (BLA).[3] The BLA was accepted for filing by the FDA in August 2024, with a Prescription Drug User Fee Act (PDUFA) target action date anticipated in the first quarter of 2025.[6]