Ticagrelor antidote shows efficacy in phase 3 trial
ACC.25 – In the REVERSE-IT trial among ticagrelor-treated patients undergoing urgent surgery or having major bleeding, bentracimab infusion resulted in rapid reversal of ticagrelor’s antiplatelet effects and effective hemostasis, with no safety concerns.
This summary is based on the presentation of Deepak Bhatt, MD (New York, NY, USA) at the ACC.25 Scientific Session - The Main Results Of The Phase 3 REVERSE-IT Trial.
Introduction and methods
The oral P2Y₁₂ inhibitor ticagrelor is a potent antiplatelet medication, but the risks of bleeding associated with invasive procedures and spontaneous major bleeding are a significant concern. As the antiplatelet effects of ticagrelor cannot be reversed with platelet transfusions, a rapid-acting reversal agent is desired.
Bentracimab is a first-in-class recombinant human monoclonal antibody that binds to free ticagrelor with high affinity and specificity. A previous phase 1 trial showed that intravenous infusion of bentracimab led to immediate and sustained reversal of ticagrelor’s antiplatelet effects.
In the REVERSE-IT (Rapid and SustainEd ReVERSal of TicagrElor – Intervention Trial) trial, a multicenter, prospective, open-label, single-arm, phase 3 trial, 226 ticagrelor-treated patients who required urgent surgery or had major bleeding received bentracimab. The primary efficacy endpoint was reversal of ticagrelor’s antiplatelet effects ≤4 hours as assessed with the VerifyNow P2Y₁₂ assay. The key secondary endpoint was effective hemostasis as assessed by an independent central adjudication committee (expected hemostasis rate: 50%).
Main results
- Within 4 hours of initiation of bentracimab infusion, reversal of ticagrelor’s effects (measured as minimum % inhibition of P2Y₁₂ reaction units) compared with baseline was observed in the overall study population (n=226), patients undergoing urgent surgery (n=141), and those with major bleeding (n=71) (all P<0.0001).
- Adjudicated effective hemostasis was found in 94.3% (95%CI: 87.6%–100%) of the study population, 100% (95%CI: 91.7%–100%) of the patients undergoing surgery, and 83.1% (95%CI: 71.5%–94.7%) of those with major bleeding (all P<0.0001).
- The frequency of drug-related adverse events was 2.2% in the overall study population, 2.1% in the surgery subgroup, and 2.8% in the major bleeding subgroup.
- There were no drug-related serious adverse events or drug-related adverse events leading to discontinuation of the study drug.
Conclusion
The final results of the REVERSE-IT trial among ticagrelor-treated patients undergoing urgent surgery or having major bleeding showed bentracimab infusion quickly reversed ticagrelor’s antiplatelet effects and resulted in effective hemostasis. There were no apparent safety concerns. Prof. Bhatt noted that the FDA granted an orphan drug designation to bentracimab last week.
- Our reporting is based on the information provided at the ACC.25 Scientific Session -