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REVERSE-IT: Bentracimab Effective in Reversing Ticagrelor Antiplatelet Effects
Data from the REVERSE-IT trial provide vital insight into the efficacy and safety of bentracimab as an FDA decision looms on the horizon.
A new “antidote” could be a game-changer for patients on ticagrelor who face urgent surgery or major bleeding, according to data presented at the American College of Cardiology (ACC) 2025 Annual Scientific Sessions.
Data from the REVERSE-IT trial suggest bentracimab, a drug designed to reverse ticagrelor’s antiplatelet effects, restored normal blood clotting within minutes. Results of the study provide additional insight into the safety and efficacy of the agent, which is currently under review by the US Food and Drug Administration.1
“If approved by the Food and Drug Administration, bentracimab could be a new life-saving option for someone having life-threatening bleeding, such as a brain hemorrhage. The same could be true in patients who need urgent or emergency surgery following a heart attack, such as coronary artery bypass grafting. Use of this drug could also allow earlier surgery in patients taking ticagrelor, by reversing its effect and allowing the surgeon to operate earlier,” says study chair Deepak L. Bhatt, MD, MPH, MBA, director of Mount Sinai Fuster Heart Hospital and the Dr. Valentin Fuster Professor of Cardiovascular Medicine at the Icahn School of Medicine at Mount Sinai.2 “Right now, there is no effective way to reverse the antiplatelet effect of ticagrelor. If approved, bentracimab would be able to fill this clinical need.”
Developed by SFJ Pharmaceuticals and set for US commercialization by SERB Pharmaceuticals, an application for bentracimab was submitted to the FDA for patients requiring urgent surgery or experiencing major bleeding while on ticagrelor in August 2024. In an interim analysis of the trial published in the New England Journal of Medicine in 2021. These data showed bentracimab reversed ticagrelor’s effects within 5 to 10 minutes, with sustained efficacy beyond 24 hours (P <.001) and more than 90% of patients achieved adjudicated hemostasis, with thrombotic events occurring in approximately 5% of cases.3
Funded by PhaseBio Pharmaceuticals, the REVERSE-IT trial was a multicenter, open-label, prospective single-arm study aimed at examining the potential reversal of the antiplatelet effects of ticagrelor with bentracimab. The primary outcome of interest for the study was the percent inhibition of P2Y12 Reaction Unit (PRU). The secondary outcome of interest was achievement of effective hemostasis, which was independently adjudicated by a clinical events committee.1
Results of the trial demonstrate a significant reduction in PRU activity following treatment with bentracimab, with the minimum percent inhibition within 4 hours post-dose decreased markedly, indicating a strong reversal of P2Y12 inhibition. Investigators pointed out this change was statistically significant (P <.0001), suggesting that bentracimab rapidly and effectively reverses the antiplatelet effects within hours of administration. Investigators also highlighted results were similar for patients in both the surgery and bleeding groups, as well as in all prespecified subgroups of patients including age and sex.1
Analysis of secondary outcomes indicated the adjudicated effective hemostasis rate was 94.3% (95% CI, 87.6% to 100% (P <.0001) in the total population. In the surgery or procedure subgroup, all patients achieved effective hemostasis (95% CI, 91.7% to 100%; P <.0001). Among patients with major bleeding, 83.1% (95% CI, 71.5% to 94.7%; P <.0001) achieved effective hemostasis.1
Similarly to the primary outcome, results for secondary outcomes were similar in both the surgery and bleeding groups and subgroups. Additionally, about 18% of patients in the surgery group experienced serious treatment-related adverse events relative to 12% in the bleeding group, but there were no study withdrawals because of these events. Investigators also pointed out 0 patients experienced serious allergic reactions to bentracimab.1
“A patient on ticagrelor who needs emergency heart surgery is at high risk for developing serious bleeding during the surgery,” Bhatt explained.2 “If you delay the surgery, there’s a risk the patient could have a heart attack. Or say a patient on ticagrelor develops bleeding in the brain. Ordinarily, we might give platelet transfusions to control the bleeding, but because of ticagrelor’s mechanism of action, platelet transfusions don’t work in patients who are taking it. Bentracimab was developed as an antidote to ticagrelor precisely for use in situations like this.”
References:
DL Bhatt. Bentracimab for Ticagrelor Reversal in Patients Undergoing Urgent Surgery – The Main Results Of The Phase 3 Reverse-it Trial. Presented at: American College of Cardiology (ACC.25) Annual Scientific Session. March 29 – 31, 2025. Chicago, Il.
American College of Cardiology. Ticagrelor Antidote Safely, Effectively Restores Platelet Function and Treats Bleeding - American College of Cardiology. American College of Cardiology. Published March 29, 2025. Accessed March 29, 2025. https://www.acc.org/About-ACC/Press-Releases/2025/03/29/15/23/Ticagrelor-Antidote-Safely.
SFJ Pharmaceuticals. FDA has accepted a bla for bentracimab, the first and only ticagrelor reversal agent, for filing and Priority Review. SFJ Pharmaceuticals. August 2, 2024. Accessed March 28, 2025. https://www.sfj-pharma.com/fda-has-accepted-a-bla-for-bentracimab-the-first-and-only-ticagrelor-reversal-agent-for-filing-and-priority-review/.
