Investigators believe the novel monoclonal antibody may be a suitable agent in patients with major bleeding risk or those undergoing surgery.
Monoclonal antibody bentracimab provided immediate and significant reversal of the bleeding effect caused by antiplatelet agent ticagrelor, according to new phase 2b data.
In a clinical trial presented at the American College of Cardiology (ACC) 2022 Scientific Sessions in Washington, DC, this weekend, investigators from Harvard Medical School and Brigham and Women’s Hospital Heart & Vascular Center showed the novel intravenous treatment bentracimab significantly restored platelet function in patients receiving oral P2Y12 inhibitor ticagrelor.
The new findings evidence the promising add-on utility of bentracimab in patients who benefit from ticagrelor’s effect on reducing risk of major adverse events from coronary disease but are also susceptible to major bleeding associated with the antiplatelet drug.
Presented by Deepak L. Bhatt, MD, MPH, executive director of interventional cardiovascular programs, the study followed promising interim data from the REVERSE-IT trial—previously presented by Bhatt at the American Heart Association (AHA) 2021 Scientific Sessions. REVERSE-IT showed bentracimab provided immediate and sustained reversal of antiplatelet effects due to ticagrelor in treated patients undergoing invasive procedures or with major bleeding.
The new phase 2b trial was a randomized, double-blind, placebo-controlled assessment that sought a primary endpoint of platelet inhibition with bentracimab bolus plus infusion, per the VerifyNow PRU test. The trial’s secondary endpoint was percent platelet inhibition per the VASP PRI test; both tests were assessed through 4 hours post-patient dose.
Investigators randomized 205 patients aged 50-80 years old receiving dual antiplatelet therapy 3:1 to bentracimab (n = 154) or placebo (n = 51). Mean patient age was 61.2 years old, with 146 (71.2%) being ≥65 years old. Approximately half of all patients were female, and 165 (80.0%) were non-Hispanic white.
Per both PRU and PRI analyses, bentracimab provided immediate antiplatelet reversal—observed before the first hour post-dose—and sustained benefit through 48 hours post-dose (P <.0001).
“Platelet function was restored to essentially baseline immediately after the bolus, with an effect that was sustained throughout the period of infusion,” investigators wrote. “There was no evidence of platelet rebound as assessed by p selectin levels or mean platelet volume.”
Investigators observed ≥1 treatment-emergent adverse event (TEAE) in 37.7% of patients administered bentracimab and 41.2% administered placebo—the most common TEAEs being headache, ecchymosis, contusions, and vessel puncture bruises. No thrombotic events nor drug-related serious adverse events were reported.
Bhatt and colleagues acknowledged a few study limitations, including that their population did not include patients with known coronary artery disease, a “modest” sample size, and lacking data on the impact of bentracimab on clinical bleeding events.
That said, the efficacy and safety findings were strong enough to indicate the novel drug’s potential in ticagrelor reversal, pending clinical data from REVERSE-IT.
“Bentracimab immediately and significantly reversed the antiplatelet effect of ticagrelor, with no related serious adverse events,” investigators concluded. “This novel approach may be useful in patients with major bleeding or undergoing emergency surgery.”
The study, “Bentracimab Immediately And Significantly Reverses The Antiplatelet Effects Of Ticagrelor In Older People,” was presented at ACC 2022.