Novel, reversible antiplatelet drug reduces risk of excessive bleeding

A phase 1 clinical trial showed that a novel antiplatelet agent, PZ-128, provides a reversible effect that reduces the risk of excessive bleeding that current antiplatelet drugs have, according to results published online December 17, 2015 in the journal Arteriosclerosis, Thrombosis and Vascular Biology.

PZ-128 is a cell-penetrating lipopeptide called a pepducin, a new type of drug that enters cells and, from the interior side of the cell membrane, acts on a specific receptor. PZ-128 targets protease-activated receptors (PAR) involved in platelet clot formation.

In this trial, researchers administered an IV dose of PZ-128 to 31 patients (average age 57) who all had multiple risk factors for coronary artery disease (CAD), including smoking, hypertension, diabetes mellitus, and dyslipidemia. More than one-fifth of subjects had documented CAD.

Researchers dosed patients with different amounts of PZ-128, and found that the effect of the drug was dose dependent. At the highest doses (1 to 2 mg/kg), PZ-128 inhibited platelet aggregation by 80% to 100%.

A subset of patients dosed with PZ-128 also received aspirin. This combination inhibited platelet aggregation by 65% to 100% within 2 hours, and 95% to 100% within 6 hours.

In addition, the drug’s platelet aggregating effect was rapidly reversible, and had cleared from some patients’ blood as quickly as 24 hours after it was given.

PZ-128 appears able to block PAR fast enough to be used in an urgent procedure, and for a time short enough to limit bleeding risk afterward, said senior author of the study Athan Kuliopulos, MD, PhD, Director of the Center for Hemostasis and Thrombosis Research at Tufts Medical Center in Boston, MA.

Dr. Kuliopulos and colleagues are now planning a phase 2 study of PZ-128 in about 600 patients undergoing angioplasty.