Phase 2b Trial of Bentracimab Supports Use in Older Patients

Deepak Bhatt, MD, MPH

Data from a phase 2b trial presented at the American College of Cardiology’s 71st Annual Scientific Sessions detail the ability of bentracimab to provide immediate and durable reversal of the antiplatelet effects of ticagrelor.

Presented by Deepak Bhatt, MD, MPH, the analysis comes less than a year after results of an interim analysis of the REVERSE-IT trial were presented at AHA 2021 and provides insight into the effects of bentracimab as a reversal agent for ticagrelor in older patients in a double-blind, placebo-controlled trial.

“Compared with placebo, bentracimab significantly restored platelet function as measured by multiple assays by binding and eliminating free ticagrelor and ticagrelor active metabolite,” said Bhatt, who serves as the executive director of interventional cardiovascular programs at Brigham and Women’s Hospital, during his presentation.

A multicenter, open-label, prospective, single-arm trial, REVERSE-IT was designed with the intent of assessing the ability of bentracimab, a monoclonal antibody from PhaseBio, for reversal of the antiplatelet effects of ticagrelor. An interim analysis off the first 140 enrolled patients, results of the interim analysis demonstrated use of bentracimab results in rates of effective hemostasis that were adjudicated as good or excellent in more than 90% of cases, with no drug-related serious adverse events, or allergic or infusion-related reactions.

The phase 2b study was a randomized, double-blind, placebo-controlled trial that randomized patients in a 3:1 ratio to bentracimab or placebo therapy. In this trial, all participants were aged 50-80 years of age and pretreated with ticagrelor and aspirin for 48 prior to receiving bentracimab. The primary outcome of interest for the trial was the inhibition of platelet reality unit (PRU).

In total, the trial enrolled 205 patients, with 154 randomized to bentracimab and 51 randomized to placebo. The overall study population had a mean age of 61.2 (SD, 6.85) years, 50.2% were male, and 80% were White.

Upon analysis, results of the trial suggested bentracimab achieved immediate and sustained reversal of antiplatelet effects among adults aged 50-80 years old who had been pretreated with dual antiplatelet therapy in both VerifyNow PRU and VASP PRI Assay analyses. In his presentation, Bhatt highlighted the effects of bentracimab on the primary endpoint were statistically significant within 4 hours and were consistent across various subgroups, including those defined by sex, age, and race.

In safety analyses, results indicated there were no drug-related serious adverse events or thrombotic events among those in the bentracimab arm. Those most common treatment-related adverse event observed in the trial were headache, ecchymosis, and contusion, but investigators highlighted there were no significant differences observed between bentracimab and placebo for any treatment-emergent adverse events in the trial.

“Based on these data, bentracimab appears to be a very promising option for ticagrelor reversal. Assessments of bentracimab’s clinical effect on patients with bleeding awaits completion of the REVERSE-IT study,” added Bhatt, in the latter portion of his presentation.

This study, “Bentracimab Immediately And Significantly Reverses The Antiplatelet Effects Of Ticagrelor In Older People,” was presented at ACC.22.