#VisualAbstract: Antibody-Based Ticagrelor Reversal Agent in Healthy Volunteers

1. A monoclonal antibody fragment to ticagrelor, PB2452, increased platelet function significantly in healthy patients given the oral P2Y₁₂ inhibitor ticagrelor.

2. Adverse effects were mainly limited to the infusion site, with limited systemic events.

Evidence Rating Level: 1 (Excellent)      

Study Rundown: Antiplatelet therapy is used extensively for prevention of cardiovascular occlusive events. Many patients receive dual-antiplatelet therapy with both aspirin and a P2Y₁₂ inhibitor. Despite stoppage of P2Y₁₂ inhibitors, patients can be at increased bleeding risk for several days after their last dose. This puts urgent surgical or invasive procedures at increased risk for excessive bleeding or can cause delay in surgery to allow the drug effect to wear off as there is no approval or effective reversal agent. PB2452 is a monoclonal antibody fragment developed as an antiplatelet agent for ticagrelor. This phase 1 study evaluated the safety and effect of PB2452. After PB2452 infusion, volunteers treated with ticagrelor had significantly increased platelet function, with maximal effect seen at 30 minutes following infusion. Following an extended PB2452 infusion, volunteers had platelet function return for up to 20 hours. Approximately one-third of participants receiving PB2452 experienced an adverse event, with most being proximal to the infusion site.

The results of this phase 1 study suggest that PB2452 can be a clinically useful ticagrelor reversal agent. Its strengths include testing of a first-in-class drug candidate and complete evaluation of safety outcomes. Its main limitation as a phase 1 study was the limited number of participants and narrow evaluation of drug efficacy.

Click to read the study in NEJM

©2019 2 Minute Medicine, Inc. All rights reserved. No works may be reproduced without expressed written consent from 2 Minute Medicine, Inc. Inquire about licensing here. No article should be construed as medical advice and is not intended as such by the authors or by 2 Minute Medicine, Inc