Monoclonal Antibody Bentracimab Shown to Reverse Antiplatelet Effect of Brilinta | ACC 2025

Bentracimab, a monoclonal antibody administered intravenously, can be an effective agent to quickly reverse the effects of the antiplatelet agent Brilinta (ticagrelor) in patients who need to have urgent surgery or who are having major bleeding, a study presented at the American College of Cardiology’s annual scientific session found.

Deepak Bhatt, M.D.

“In patients undergoing urgent surgery or with major bleeding, bentracimab significantly restored platelet function,” said Deepak Bhatt, M.D., director of Mount Sinai Heart in New York, who presented results of the phase 3 REVERSE-IT trial during the late-breakers’ session. Trial results were also published simultaneously in the New England Journal of Medicine Evidence.

Brilinta, developed by AstraZeneca, is an oral P2Y₁₂ inhibitor used in combination with aspirin to prevent a heart attack or stroke in people with acute coronary syndrome or who have had a heart attack and to prevent repeat heart attacks and blood clots in people who have had a stent placed in a coronary artery.

“Ticagrelor at this point in time has a ton of randomized-clinical-trial data supporting it and broad Food and Drug Administration labeling, also including patients with high-risk coronary artery disease, transient ischemic attack and stroke,” Dr. Bhatt said. It is expected to be available as a generic worldwide “in the next couple years, so its use will be likely to increase.”

However, as with any antiplatelet medication, bleeding can be a problem, he said. What differentiates Brilinta from other anticoagulant drugs is its proclivity to bind to the P2Y₁₂ platelet receptor. Bentracimab binds to free Brilinta, which allows adenosine diphosphate to activate platelets while the bentracimab/ticagrelor complex is eliminated from the bloodstream.

The FDA last year accepted the biologic license application for bentracimab and this year granted it orphan drug designation. If approved, bentracimab will be marketed in the United States by SERB Pharmaceuticals.

The REVERSE-IT trial was funded initially by PhaseBio and then by SFJ Pharma. PhaseBio and SFJ were codevelopers of bentracimab. PhaseBio had filed for bankruptcy in 2022, and bentracimab was transferred to SFJ Pharma by the bankruptcy court in January 2023.

REVERSE-IT enrolled 226 patients who had used Brilinta within three days before needing urgent surgery or having major bleeding. The researchers expected a 50% rate of normal platelet activation upon starting the trial, Dr. Bhatt said. In the trial, normal platelet reactivation, measured by the VerifyNow P2Y₁₂ (PRU) assay, occurred in 80.5% of patients within five to 10 minutes and in 91.2% within 30 minutes after starting bentracimab treatment.

Dr. Bhatt noted that effective hemostasis was achieved in 95% of all eligible study participants, including all surgery patients and 79.5% of bleeding patients (p<0.0001).

“The safety profile looked good,” Dr. Bhatt said, noting that five patients had a drug-related adverse event, a rate of 2.2% overall.

One limitation of the study was that it did not include a placebo arm, but Bhatt pointed out that the platelet function results in REVERSE-IT were consistent with the randomized phase 1 trial. And, he said, “the sample size was modest.”

“Based on REVERSE-IT, bentracimab appears to be a very promising option for ticagrelor reversal,” Bhatt said.

Toby Trujillo, Pharm.D.

With Brilinta going generic worldwide in the next few years, its use will “continue to likely increase,” said Toby Trujillo, Pharm.D., professor of clinical pharmacy at University of Colorado Anschutz Medical Campus in Aurora and member of the ACC cardiovascular team pharmacist working group.

“While it is an effective antiplatelet, it does come with a risk of bleeding,” Dr. Trujillo said of Brilinta, “and unlike other anticoagulants that we’re used to dealing with, there is no really good option to reverse the antiplatelet effect of the agent. You can’t transfuse platelets; there are other hemostatic approaches that don’t have good support in the literature.

“So, the ability to reverse the antiplatelet effect in a clinical situation where you deem that’s going to help improve the patient’s clinical outcome, either major bleeding or in urgent surgery, is going to be a welcome addition in our ability to manage these patients.”