Ticagrelor Finds a Quick, Effective Reversal Agent in Bentracimab: REVERSE-IT Early Data

Key Points:

• To date, P2Y-12 inhibitors do not have a commercially approved reversal agent.
• The use of ticagrelor, which unlike clopidogrel and prasugrel, reversibly inhibits platelets has increased over the past years, as clinical trial data emerge in favor of its use.
• Bentracimab is a recombinant IgG1 monoclonal antibody that reverses the effect of ticagrelor.
• In this phase 3 clinical trial, 150 patients on ticagrelor who had upcoming surgery or experienced bleeding were infused with bentracimab. Platelet inhibition was achieved within four hours of infusion and was sustained for twenty-fours, verified by two different platelet reactivity assays (p<0.001).

The use of P2Y-12 inhibitors can often be challenging in urgent clinical settings, i.e. urgent or emergent surgery and intracranial hemorrhage. Unlike vitamin K antagonists, there are no commercially available reversal agents for P2Y-12 inhibitors, despite a high prevalence of their prescription and use.

During a late breaking session at the 2021 American Heart Association Scientific Sessions, Dr. Deepak Bhatt (Brigham and Women’s Hospital, Boston) presented findings of REVERSE-IT, a phase 3 clinical trial assessing the efficacy and safety of bentracimab, a novel reversal agent of ticagrelor. Bentracimab is a recombinant IgG1 monoclonal antibody that reverses the platelet inhibition effects of ticagrelor, which unlike clopidogrel and prasugrel, reversibly binds to its platelet receptor.

In this open-label single arm study, patients who were undergoing urgent surgery (n=142) or suffering from bleeding episodes (n=8) were enrolled and received the drug. Patients were included if they were at least 18 years of age and had a dose of ticagrelor within three days. In the prespecified interim analysis, platelet inhibition was seen at 5 minutes and minimum inhibition of 50% of the drug was met within four hours of infusion, and was sustained for 24 hours. Inhibition was assessed using the VerifyNow assay and the VASP platelet reactivity index. In patients undergoing surgery, hemostasis was achieved in all, with a 39% rate of transfusion. In bleeding patients, hemostasis was achieved in 78% of patients, with 63% requiring a transfusion. After studying P-selectin and mean platelet volumes, no evidence of platelet rebound activity was found within 72 hours.

When discussing the results of the trial Dr. Bhatt said that he would expect approval of the drug to be limited to “the conditions that were studied.” He added, “the drug is not available for commercial or compassionate use at the moment, but the study is very reassuring nonetheless”.  Dr. Bhatt expects that bentracimab will make significant headway toward approval in U.S and Europe.