Phase 2B Study to Evaluate the Efficacy of PB2452 in Reversal of Ticagrelor in Subjects Aged 50-80 - Bentracimab

Apr 02, 2022
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Author/Summarized by Author:
Dharam J. Kumbhani, MD, SM, FACC
Summary Reviewer:
Kim A. Eagle, MD, MACC
Trial Sponsor:
PhaseBio Pharmaceuticals
Date Presented:
04/02/2022
Original Posted Date:
04/02/2022
References

Contribution To Literature:

This phase 2b trial showed that bentracimab is safe and effective in quickly reversing the antiplatelet effect of ticagrelor in older healthy volunteers.

Description:

The goal of the trial was to assess the safety and efficacy of bentracimab in reversing the antiplatelet effect of ticagrelor.

Study Design

This was a phase 2b trial. After a screening phase for 30 days, volunteers received dual antiplatelet therapy with aspirin and ticagrelor for 48 hours, at which point they were stopped and then randomized in a 3:1 fashion to either bentracimab (n = 154) or placebo (n = 51).

  • Total number of enrollees: 205
  • Duration of follow-up: 48 hours
  • Mean volunteer age: 61 years
  • Percentage female: 50%

Inclusion criteria:

  • Healthy adults aged 50-85 years

Exclusion criteria:

  • Contraindication to ticagrelor
  • Severe chronic kidney disease (CKD)

Other salient features/characteristics:

  • White: 80%
  • Mild CKD: 59%, moderate CKD: 9%
  • Mean body mass index: 28 kg/m2

Principal Findings:

The primary endpoint, minimum % inhibition of P2Y12 reaction units (PRU) within 4 hours, was significantly lower with bentracimab compared with placebo (p < 0.0001). PRU change was seen as early as 5-10 minutes post-infusion. The effect appeared robust among all subgroups tested. Based on soluble P-selectin analysis and mean platelet volume analysis, there was no apparent rebound platelet activation in both groups.

There were no thrombotic events and no deaths.

Interpretation:

The results of this phase 2b trial indicate that bentracimab, a recombinant IgG1 monoclonal antibody antigen-binding fragment that binds with high affinity to ticagrelor and its active metabolite (AR-C124910XX), is safe and effective in quickly reversing the antiplatelet effect of ticagrelor in older healthy volunteers.

Although clinical bleeding endpoints were not specifically assessed, this drug may be potentially useful for patients where timely ticagrelor reversal is essential (significant bleeding, need for emergent surgery). This hypothesis is specifically being tested in the REVERSE-IT trial. This drug is not expected to work against clopidogrel and prasugrel, which are irreversible P2Y12 receptor inhibitors.

References:

Presented by Dr. Deepak L. Bhatt at the American College of Cardiology Annual Scientific Session (ACC 2022), Washington, DC, April 2, 2022.

Clinical Topics: Acute Coronary Syndromes, Anticoagulation Management, Cardiac Surgery, Geriatric Cardiology, Invasive Cardiovascular Angiography and Intervention, Anticoagulation Management and ACS, Novel Agents, Interventions and ACS

Keywords: ACC22, ACC Annual Scientific Session, Acute Coronary Syndrome, Antibodies, Monoclonal, Anticoagulants, Aspirin, Cardiac Surgical Procedures, Clopidogrel, Geriatrics, Hemorrhage, Immunoglobulin G, Platelet Activation, Platelet Aggregation Inhibitors, Prasugrel Hydrochloride, P-Selectin, Purinergic P2Y Receptor Antagonists, Renal Insufficiency, Chronic, Ticagrelor


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