Phase 1c Study Demonstrates Dose-dependent Activity of Antidote Component
DURHAM, N.C., May 14 /PRNewswire/ -- Regado Biosciences today announced the Journal of Thrombosis and Haemostasis, the official journal of the International Society on Thrombosis and Haemostasis, has published the Phase 1c clinical results of the Company's REG1 anticoagulation system. REG1 is a two-component system comprised of an aptamer-based anticoagulant, RB006, and its matched antidote, RB007, which binds to and neutralizes RB006. The published study demonstrated RB007's ability to reverse the anticoagulant effect of RB006 either completely or partially, depending on the level of dosing of RB007.
The article, titled "A randomized, repeat dose, pharmacodynamic, and safety study of an antidote-controlled factor IXa inhibitor," was authored by Mark Y. Chan, Duke Clinical Research Institute (DCRI); Christopher P. Rusconi, Regado Biosciences; John H. Alexander, DCRI; Ross M. Tonkens, Regado; Robert A. Harrington, DCRI; and Richard C. Becker, DCRI. The study showed repeated doses of RB006 achieved highly reproducible increases in activated partial thromboplastin time (aPTT), a well-accepted surrogate marker of the blood's ability to clot. Subsequently, administration of RB007 reversed the aPTT levels dose-dependently and reproducibly. There were no major bleeding episodes or other serious adverse events reported in this study.
"The Phase 1c results provide important validation of the activity of the REG1 system in the clinical setting," stated Doug Gooding, Chief Executive Officer of Regado Biosciences. "Specifically, the study confirmed the ability for physicians to titrate the RB007 component and therefore reverse or neutralize the anticoagulant effect of RB006. If the remainder of our clinical studies confirms these results, this flexibility represents a potentially significant advance in anticoagulation therapy. We are very pleased these results have been published in a prestigious, clinically oriented, peer-reviewed publication."
Results from Regado's 1c study were presented previously at the American Heart Association's 2007 Scientific Sessions.
About REG1 Anticoagulation System Clinical Program
In the Phase 1c clinical study, the researchers randomized 39 healthy volunteers to receive either three consecutive REG1 treatment cycles or placebo. Each REG1 cycle consisted of an intravenous (IV) bolus of RB006 dosed at 0.75 mg/kg, followed an hour later by a descending dose of RB007, ranging from a 2:1 to 0.125:1 antidote:drug ratio (1.5 mg/kg to 0.094 mg/kg of RB007). Clinical and coagulation assessments were measured for 14 days.
The Phase 1 program included two additional studies. A Phase 1a study enrolled 84 healthy volunteers, while a Phase 1b study enrolled 50 patients with stable coronary artery disease who were receiving aspirin with or without clopidogrel. The results showed an IV bolus injection of RB006 achieved, in both study populations, a prompt, consistent, and dose-dependent prolongation of activated partial thromboplastin time (aPTT). In addition, a 1 mg/kg dose of RB006 resulted in essentially complete Factor IXa inhibition. The studies also demonstrated an IV bolus injection of RB007 administered in a 2:1 antidote:drug ratio successfully reversed prolonged aPTT within a median of one minute, with no rebound increase up to seven days. Despite dual antiplatelet use in 19 subjects, there were no major bleeding or other serious adverse events observed in either study.
Based upon the combined results of the Company's Phase 1a, 1b, and 1c studies, Regado initiated REVERSAL-PCI, a multi-center, open-label, randomized Phase 2a clinical study of the REG1 anticoagulation system. The Phase 2a study is enrolling 26 patients undergoing elective percutaneous coronary intervention (PCI) to assess whether REG1 can replace standard heparin therapy during the performance of coronary balloon angioplasty dilatation and stenting in patients at low risk for complications associated with therapy-related bleeding or heart attack.
About REG1 Anticoagulation System
Regado's lead product candidate, REG1, is the first specific, direct-acting, antidote-controlled anticoagulant ever described. Regado is developing REG1 for use in patients suffering from acute coronary syndrome who undergo coronary revascularization procedures. These procedures, which include coronary artery bypass grafting (CABG) and percutaneous coronary intervention (PCI), put patients at a high-risk for therapy-related bleeding complications. REG1 is being developed initially to increase therapeutic flexibility and improve patient outcomes in coronary revascularization procedures.
REG1 is a two-component system, consisting of an aptamer-based anticoagulant and its matched antidote. The REG1 anticoagulant component, RB006, is a single-stranded, nucleic acid aptamer. RB006 selectively and potently binds to and inhibits Factor IXa, a protein that is critical to blood coagulation. The antidote component, RB007, is a complementary nucleic acid that binds to and neutralizes RB006. The binding of RB007 to RB006 causes the predictable and rapid reversal of RB006 that allows the patient's blood to return to normal.
About Regado Biosciences
Regado Biosciences is pioneering a new therapeutic field with the discovery and development of drug:antidote systems. Regado's drug:antidote systems are designed to give physicians the ability to fine-tune the therapeutic effect desired for each patient and in each setting. A spin-out of the Department of Surgery at Duke University Medical Center, Regado was created to answer the therapeutic needs identified by its scientific founders.
The Company's proprietary platform technology enables the discovery of oligonucleotide-based drug-antidote pairs to any target protein. Regado initially is focusing its discovery and development efforts on the acute care injectable antithrombotics, a multi-billion dollar market in need of therapeutics with improved safety profiles. Potential future indications for Regado's technology include acute coronary syndromes and other coronary revascularization procedures that would benefit from the availability of an antidote-reversible agent.
|SOURCE Regado Biosciences|
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