Phase 1 clinical data show that subcutaneous administration of RUC-4 resulted in a potent, rapid, and sustained platelet inhibition effect; RUC-4 was safe and well tolerated in patients with stable coronary artery disease (CAD) who are taking aspirin
SAN DIEGO–(BUSINESS WIRE)–CeleCor Therapeutics, Inc. announced positive data from the company’s completed phase 1 clinical study of RUC-4, a novel subcutaneous platelet GPIIb/IIIa inhibitor designed as a first point-of-contact therapy for ST-Elevation Myocardial Infarction (STEMI), which was presented today in a late-breaking oral presentation at the American Heart Association (AHA) Scientific Sessions 2019 in Philadelphia. The study met its primary endpoint with a 0.075 mg/kg subcutaneous dose of RUC-4 that provided rapid (<15 minute following subcutaneous administration), intense (>80%), and sustained (<2 hours) inhibition of platelet aggregation. The data support the further development of RUC-4 as a first point-of-contact therapy for STEMI, a serious type of heart attack, during which one of the heart's major arteries is blocked.
“RUC-4 did exactly what we hoped it would do and met the trial primary endpoint of 80% platelet inhibition within 15 minutes of treatment. This is a clinically relevant endpoint as it has been shown to correlate with improved clinical outcomes following percutaneous coronary intervention in heart attack patients,” said Dean J. Kereiakes, M.D., FACC, FSCAI, Medical Director of The Christ Hospital Heart and Vascular Center and the Christ Hospital Research Institute, Professor of Clinical Medicine at The Ohio State University, and Principal Investigator for the phase 1 study. “Based on this study’s success, we believe RUC-4 is an attractive candidate for first point-of-contact STEMI therapy and could fulfill a significant unmet medical need in the pre-hospital phase of heart attack care.”
Inhibiting platelet aggregation can slow or stop blood clot formation leading to coronary artery blockage, and in turn, can stop or prevent a heart attack. By targeting platelet GPIIb/IIIa receptors, the final common pathway in platelet aggregation, RUC-4 inhibits platelet aggregation caused by all platelet activators and can, under some conditions, promote platelet disaggregation (clot dissolution). In contrast, other antiplatelet medications, including P2Y12 inhibitors and aspirin, inhibit only one platelet activator and do not disaggregate existing clots. Further, oral P2Y12 inhibitors do not act rapidly or reliably enough in STEMI patients during the crucial early minutes of a heart attack.
“RUC-4 is a major breakthrough that combines the potent platelet inhibition of GPIIb/IIIa inhibitors with a simple, single subcutaneous injection by auto-injector,” said C. Michael Gibson, M.S., M.A. (Hon.), M.D., FRCP, FAHA, FSCAI, FACC, scientific advisor to CeleCor. “As a GPIIb/IIIa inhibitor, RUC-4 blocks all platelet aggregation pathways and can provide dose-dependent disaggregation of existing platelet-rich thrombi to improve outcomes for heart attack patients.”
This clinical study assessed the safety, tolerability, pharmacokinetics, and pharmacodynamics of escalating doses of RUC-4 administered subcutaneously in healthy volunteers as well as in patients with stable coronary artery disease (CAD) who are taking aspirin. The data presented from 44 participants (14 healthy volunteers, 30 stable CAD patients with aspirin) showed that RUC-4 at a 0.075 mg/kg dose provides rapid (<15 minute), intense (>80%), and short-term (<2 hours) inhibition of platelet aggregation after subcutaneous treatment. The safety data showed no bleeding events, no drug-related ECG changes, no serious adverse events (SAEs), no thrombocytopenia, and no drug-related changes in laboratory values. In addition, aspirin did not significantly affect RUC-4 pharmacokinetics or pharmacodynamics, nor did it increase bleeding.
Robert S. Hillman, President and CEO of CeleCor, said, “Despite important advances in hospital care of heart attack patients, a significant portion of heart attack victims die before reaching the hospital, and pre-hospital mortality is unchanged over the past 40 years. That’s why we specifically designed RUC-4 for easy early administration as a single subcutaneous injection by auto-injector. We are now finishing the design of a phase 2 study of RUC-4 for the pre-hospital treatment of STEMI patients and are committed to rapidly advancing RUC-4 through clinical trials.”
About RUC-4 and GPIIb/IIIa inhibitors (GPIs)
The current FDA-approved GPIIb/IIIa inhibitors (abciximab, eptifibatide, and tirofiban) have demonstrated improved clinical outcomes when administered to STEMI patients at the first point-of-contact, but they require an intravenous bolus dose, followed by an ongoing intravenous administration controlled by an infusion pump. This limits their ability to be administered in a pre-hospital setting. RUC-4 is differentiated from current GPIIb/IIIa drugs by its subcutaneous route of administration, and its capacity to lock the receptor in its inactive state. RUC-4 is specifically designed for easy early administration as a single subcutaneous injection by auto-injector so as to facilitate its use as the first point-of-contact treatment for STEMI.
About CeleCor Therapeutics
CeleCor Therapeutics, Inc. is a biotechnology company focused on developing a first-point-of-contact therapy to improve the treatment of serious heart attacks, specifically ST-Elevation Myocardial Infarction (STEMI). The company’s lead product candidate, currently in clinical trials, is RUC-4, a novel small molecule inhibitor of the platelet GPIIb/IIIa (αIIbβ3) receptor, designed to be easily administered subcutaneously by auto-injector at the first point-of-contact. CeleCor is headquartered in San Diego. For more information, visit www.celecor.com.
Robert S. Hillman, Ph.D.