PB2452 Effective at Quickly Reversing Antiplatelet Effects of Ticagrelor

Illustration of human blood cells.
Investigators sought to determine whether the administration of PB2452, a specific reversal agent for ticagrelor, could reverse the antiplatelet effects of ticagrelor quickly and effectively.

PB2452 has demonstrated efficacy in quickly reversing the antiplatelet effects of ticagrelor, according to study results recently published in the New England Journal of Medicine. These results were confirmed in multiple platelet assays and included few small toxic effects.

This double-blind, placebo-controlled, phase 1 trial included 64 healthy volunteers (age 18-50 years; weight, 50-120 kg; body mass index, 18-35 kg/m2) who were randomly assigned to receive intravenous PB2452 (n=48) or placebo (n=16). Platelet function was examined among healthy volunteers at baseline, after 2 days of pretreatment with ticagrelor, and after initiation of PB2452 or placebo. Light transmission aggregometry, a vasodilator-stimulated phosphoprotein assay, and a point-of-care P2Y12 platelet-reactivity test were used to examine platelet function. The study’s primary efficacy outcome was reversal of the antiplatelet effects of ticagrelor; the primary safety outcome was prevalence and severity of adverse events after administration of either PB2452 or placebo. Spearman’s rank-collection coefficient and Pearson’s correlation coefficient were used to examine the association between platelet function tests.

After 2 days of pretreatment with ticagrelor, there was approximately an 80% rate of platelet aggregation suppression, with an intravenous bolus of PB2452 followed by a longer infusion correlating with significantly better platelet function rates compared with placebo. The initiation of PB2452 resulted in ticagrelor reversal within a 5-minute window that was sustained for >20 hours (P <.001 with Bonferroni adjustment). After drug cessation, no rebound in platelet activity was observed. Significant correlation was found for the results in all 3 platelet-function tests (Pearson’s r values ≥0.91; Spearman’s r value ≥0.81; P <.001 for all). Adverse events related to the trial drug were mainly limited to infusion site issues.

Limitations to this study include the use of healthy volunteers instead of persons with atherosclerosis, a small sample size, and a lack of predictive value among individuals with bleeding.

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The study researchers concluded that “the administration of intravenous PB2452 reversed the antiplatelet effects of ticagrelor, as measured by multiple assays of platelet function, and was associated with minimal low-grade toxic effects.”

This study was funded by PhaseBio Pharmaceuticals.


Bhatt DL, Pollack CV, Weitz JI, et al. Antibody-based ticagrelor reversal agent in healthy volunteers. N Engl J Med. 2019;380(19):1825-1833.