Bentracimab ‘promising option’ for quick, sustained ticagrelor reversal in older adults
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WASHINGTON — The IV monoclonal antibody bentracimab immediately and significantly reversed the antiplatelet effect of ticagrelor in healthy older adults, with no related serious adverse events, researchers reported.
Ticagrelor (Brilinta, AstraZeneca) is an effective antiplatelet agent but if bleeding occurs there is no way to reverse it, Cardiology Today Intervention Section Editor Deepak L. Bhatt, MD, MPH, executive director of interventional cardiology programs at Brigham and Women’s Hospital and professor of medicine at Harvard Medical School, said during a presentation at the American College of Cardiology Scientific Session. Bentracimab (PhaseBio) is a human monoclonal antibody fragment designed to bind to ticagrelor and may be useful in patients who have major bleeding or are undergoing emergency surgery, Bhatt said.
“Compared with placebo, bentracimab significantly restored platelet function as measured by multiple assays by binding and eliminating free ticagrelor and also free ticagrelor active metabolite,” Bhatt said. “There were no thrombotic events and no serious adverse events reported in these volunteers randomized to bentracimab, affirming the safety profile. Based on these data, bentracimab appears to be a very promising option for ticagrelor reversal.”
As Healio previously reported, in a prespecified interim analysis of the REVERSE-IT trial, bentracimab provided immediate and sustained reversal of ticagrelor’s antiplatelet effects in ticagrelor-treated patients undergoing invasive procedures or with major bleeding. In REVERSE-IT, the percent inhibition of platelet function as assessed by the platelet reactivity index was lower than before dosage of bentracimab at 4 hours, as well as at all time intervals up to 24 hours.
For a new phase 2b trial, Bhatt and colleagues analyzed data from 205 adult volunteers aged 50 to 80 years who were pretreated with ticagrelor and aspirin for 48 hours and then randomly assigned to bentracimab bolus plus infusion (n = 154) or placebo (n = 51). The primary endpoint was percent platelet inhibition as assessed by the VerifyNow platelet reactivity unit test. The secondary endpoint was percent platelet inhibition by the VASP PRI test, both assessed through 4 hours after dosing.
The primary and secondary endpoint each demonstrated a significant reversal of ticagrelor’s effect (P < .0001 for both). Platelet function was restored to baseline immediately after the bolus, with an effect that was sustained throughout the infusion period. Results were consistent across subgroups stratified by sex, race, diabetes and hypertension status, Bhatt said. Researchers did not observe evidence of platelet rebound when assessing markers of platelet activation.
There were no serious adverse events related to bentracimab.
Bhatt noted that the study’s sample size was modest; however, it was well-powered for pharmacodynamic endpoints, and all platelet assay results were consistent and statistically significant. The study was not designed to evaluate the impact of bentracimab on clinical bleeding events.
“Assessment of bentracimab’s clinical effect on patients with bleeding awaits completion of the REVERSE-IT study, which is ongoing and continuing to enroll patients,” Bhatt said.
In discussion following the presentation, Binita Shah, MD, assistant professor of medicine and associate director of the cardiac cath lab research program at NYU Grossman School of Medicine, said potential bleeding events in high-risk patients comes with a rebound of platelet activity and ischemic events, possibly related to the role of inflammation in the setting of trauma.
“Life happens — accidents, falls, unplanned cardiac surgery,” Shah said. “[Bentracimab] is an important drug to have in our armamentarium, given the scope of patients who are now on more potent P2Y12 inhibitors.”
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Bhatt DL, et al. Featured Clinical Research I. Presented at: American College of Cardiology Scientific Session; April 2-4, 2022; Washington, D.C. (hybrid meeting).
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