The novel subcutaneously administered glycoprotein IIb/IIIa antagonist RUC-4 (Zalunfiban) did not cause thrombocytopenia in the phase 2a study of patients with ST-elevation myocardial infarction

Abstract

Abstract Funding Acknowledgements Type of funding sources: Private company. Main funding source(s): Celecor Therapeutics Background/Introduction Thrombocytopenia is a rare but severe complication (0.5%-2.0%) of all currently available glycoprotein IIb/IIIa inhibitors (GPI). As thrombocytopenia is inherently linked to bleeding, careful consideration is mandated in ST-elevation myocardial infarction (STEMI) patients as they require multiple antithrombotic medications. Moreover, thrombocytopenia is associated with poor clinical outcomes in comparison to patients without thrombocytopenia. Thus, there is a need for safer GPIs that are not associated with drug-induced thrombocytopenia. Zalunfiban is a novel, second-generation GPI primarily designed for the pre-hospital phase to initiate target vessel reperfusion. In addition, Zalunfiban has a unique mechanism of action that locks the receptor into an inactive conformation, potentially decreasing the likelihood of developing thrombocytopenia. In healthy individuals and in patients with stable coronary artery disease treated with Zalunfiban, no thrombocytopenia was seen. Purpose To assess the occurrence of thrombocytopenia of Zalunfiban in STEMI patients. Methods This was a prospective, single centre, open-label, phase 2a study designed to assess the pharmacodynamics, pharmacokinetics, and tolerability of Zalunfiban in patients with STEMI undergoing primary percutaneous coronary intervention. The primary endpoint in this sub-analysis was the occurrence of thrombocytopenia, defined as a platelet count less than 150 × 10^9/L, as measured at 4 time points up to 72 hours after drug administration. Secondary analyses were laboratory assessments including haemoglobin, creatinine and liver function tests. Results A total of 27 patients received a weight-adjusted subcutaneous injection of Zalunfiban in escalating doses (0.075 mg/kg [n=8], 0.090 mg/kg [n=9], or 0.110 mg/kg [n=10]). No thrombocytopenia (0.0%) was observed within the first 72 hours post dose. Also, haemoglobin, creatinine and liver function tests were stable during hospitalisation. Conclusion In this sub-analysis Zalunfiban did not cause thrombocytopenia in the 27 patients enrolled in the study, which is in accord with the lack of thrombocytopenia in the 44 patients receiving Zalunfiban in the Phase 1 studies in healthy volunteers and stable angina patients. The ongoing CELEBRATE study, in which Zalunfiban is administered in the ambulance, is scheduled to enrol 1667 STEMI patients and thus will provide important additional information on Zalunfiban safety and efficacy.