Targeting ticagrelor: a novel therapy for emergency reversal

Newer P2Y12 inhibitors are prescribed in place of clopidogrel for patients with acute coronary syndrome (ACS) and are associated with significant bleeding risks. Currently, limited options exist for the management of life-threatening bleeding or acute reversal for patients on P2Y12 inhibitor therapy, specifically ticagrelor. Various interventions, including platelet transfusion and desmopressin, have been studied for ticagrelor reversal demonstrating limited success. PB2452 is a novel monoclonal antibody which binds to both ticagrelor and its active metabolite resulting in a rapid return of platelet aggregation. PB2452 has been studied in animal models and, most recently, in a Phase I trial in healthy volunteers. In animal models, PB2452 displayed rapid reversal of ticagrelor and its metabolites and return to near normal levels of platelet aggregation within 60 min. In healthy human volunteers, cohorts that received higher dose bolus and infusions of PB2452 over 12-16 h resulted in maximal and sustained reversal of ticagrelor inhibition of platelet aggregation. While it is currently not US Food and Drug Administration approved, future Phase 2 and 3 studies are currently underway that may lead to new directions for patients on ticagrelor therapy who require urgent reversal.