Researchers report promising results of a potential reversal agent

In patients with acute coronary syndrome, coronary artery stenting, or a history of heart attack, antiplatelet therapy can be life-saving. Ticagrelor, in combination with aspirin, is commonly prescribed to patients to help prevent blood clotting and subsequent cardiovascular events. But ticagrelor increases the bleeding risk of these patients and its effects persist even several days after stopping treatment. This is an important concern for patients at risk of major bleeding, such as intracranial or gastrointestinal bleeding, and for patients who may require urgent or urgent surgery. Currently, no fast-acting agent is available to reverse the effects of ticagrelor. In a randomized, double-blind, placebo-controlled Phase 1 study in healthy volunteers, a group led by Deepak L. Bhatt, MD, MPH, Brigham's Executive Director of Cardiovascular Interventional Programs and Professor of Medicine at Harvard Medical School, reported promising results on a potential reversal agent. The findings of Bhatt and his colleagues suggest that this agent, known as PB2452, allows an immediate and lasting reversal of the effects of ticagrelor. Their findings were presented during a clinical research session presented at the 68th Annual Scientific Session of the American College of Cardiology and were published simultaneously in The New England Medical Journal.

"Ticagrelor is a very effective agent and recommended as a first-line treatment, but if a patient presents with heavy bleeding or needs urgent or urgent intervention, we face a major challenge," said Bhatt, the main author of this work. "Having an inversion agent able to work quickly and efficiently would be a big step forward for the sector."

PB2452, developed by the study sponsor, PhaseBio Pharmaceuticals, Inc., is a fragment of monoclonal antibody that binds to ticagrelor with high affinity. In the study, 64 healthy volunteers aged 18 to 50 years who had been pretreated with ticagrelor received various doses of PB2452 intravenously or from a placebo. The team evaluated the efficacy of PB2452 by badyzing platelet function using several methodologies.

Of the 48 volunteers pretreated with ticagrelor, platelet aggregation was suppressed by approximately 80%. After administration of PB2452, suppression of platelet aggregation by ticagrelor was reversed within five minutes and was maintained for more than 20 hours.

No serious adverse reactions or infusion reactions badociated with PB2452 were observed. A total of 30 treatment-emergent adverse events (27 of those receiving PB2452 and 3 of those receiving placebo) were primarily related to infusion site problems. The team noted some limitations to the study, including that the participants were healthy volunteers, not patients with atherosclerosis, and that the sample size was relatively small.