Initial phase 1 clinical data demonstrated that subcutaneous administration of RUC-4 resulted in a potent, rapid, and sustained platelet inhibition effect and was safe and well tolerated
SAN DIEGO–(BUSINESS WIRE)–#TCT2019—CeleCor Therapeutics, Inc. today announced preliminary positive results in the company’s ongoing phase 1 clinical study with RUC-4, a novel subcutaneous platelet GPIIb/IIIa inhibitor, presented at Transcatheter Cardiovascular Therapeutics (TCT) 2019 in San Francisco. The data support the further development of RUC-4 as a first point-of-contact therapy for ST-Elevation Myocardial Infarction (STEMI), a serious type of heart attack, during which one of the heart’s major arteries is blocked. These data will also inform the design of a phase 2 study to investigate the efficacy and safety of RUC-4 following subcutaneous administration for the pre-hospital treatment of STEMI patients.
Early treatment of heart attacks prevents death and loss of cardiac muscle, which translates into both improved long-term survival and reduced incidence of heart failure that may seriously compromise a patients’ functional capacity. 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. 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, GPIIb/IIIa agents inhibit platelet aggregation caused by all activators and can even, under some conditions, promote platelet disaggregation. 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, followed by an ongoing intravenous infusion, limiting their ability to be administered in a pre-hospital setting. In contrast, other antiplatelet medications, including P2Y12 inhibitors and aspirin, inhibit just one activator. 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 specifically designed for early and easy administration as a single subcutaneous injection by auto-injector so as to facilitate its use as the first point-of-contact treatment for STEMI. Further, 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. The results of the Phase 1 study demonstrate that it can deliver rapid onset and limited duration platelet inhibition and we look forward to advancing it rapidly in the clinic,” said Robert S. Hillman, President and CEO of CeleCor.
“This first-in-human data indicate that RUC-4 delivers prompt, potent, and predictable inhibition of platelet aggregation,” said C. Michael Gibson, M.S., M.A. (Hon.), M.D., FRCP, FAHA, FSCAI, FACC, scientific advisor to CeleCor. “Combined with the ability to produce dose-dependent disaggregation of platelet-rich thrombi, RUC-4 administration in a pre-hospital setting could provide significant benefit for improving outcomes in STEMI.”
Clinical Study Results
This clinical study is assessing 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 at TCT 2019 from 30 participants (14 healthy volunteers, 16 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 preliminary 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. All injection site reactions were mild, except one that was moderate.
“The subcutaneous administration of RUC-4 at a 0.075 mg/kg dose in patients with stable coronary artery disease who are taking aspirin showed a rapid onset of action in less than 15 minutes, with potent platelet inhibition of 80 percent or greater and an effect lasting less than two hours,” 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 the initial safety, tolerability, and efficacy data from this clinical study, we believe RUC-4 is an attractive candidate for first point-of-contact therapy of STEMI and could fulfill a significant unmet medical need in pre-hospital heart attack care.”
The presentation entitled, “First Human Use of a Novel Subcutaneous Platelet GPIIb/IIIa Inhibitor (RUC-4) Designed for STEMI Point of Care Treatment,” will be presented on September 27 at 4:00 PM PDT at TCT 2019 in Moscone Center South in San Francisco.
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.