Regado Biosciences, Inc., a privately held company pioneering the development of antithrombotic aptamers with active control agents, announced today the primary results of the RADAR Phase 2b clinical trial of the company's lead product, the anticoagulation system REG1, at the i2 Summit during the American College of Cardiology 2011 60th Annual Scientific Session & Expo in New Orleans, LA. REG1 is a two-component system consisting of pegnivacogin, a highly selective Factor IXa (FIXa) inhibitor and anivamersen, its complementary specific active control agent.
The presentation, "A Randomized, Partially-Blinded, Multi-Center, Active-Controlled, Dose-ranging Study Assessing the Safety, Efficacy and Pharmacodynamics of the REG1 Anticoagulation System Compared to Unfractionated Heparin or Low Molecular Weight Heparin in Subjects with Acute Coronary Syndromes: Primary Results of the RADAR Randomized Clinical Trial," was made by Thomas J. Povsic, MD, PhD, Assistant Professor of Medicine at Duke University during an i2 Special Session titled "Interventional Featured Clinical Studies I."
The international Phase 2b RADAR clinical trial was conducted in subjects admitted for ACS-unstable angina and myocardial infarction without ST-segment elevation (UA/NSTEMI) intended for cardiac catheterization within 24 hours. The objectives of RADAR were to verify that 1 mg/kg of pegnivacogin resulted in near complete FIXa inhibition, to determine the dose of anivamersen which, when followed by immediate arterial sheath removal, results in a bleeding rate lower than heparin and to assess the efficacy of REG1 (based on ischemic event rates) as an anticoagulant system in an invasively managed ACS population. The primary endpoint of the study was ACUITY bleeding (major and minor) at 30 days. A secondary endpoint was a composite of death, myocardial infarction (MI), urgent target vessel revascularization (TVR) or recurrent ischemia at 30 days.
Previously presented data from RADAR (AHA, November 2010) confirmed that pegnivacogin dosed at 1mg/kg reproducibly resulted in near complete inhibition of FIXa in an ACS population. The latest RADAR results showed that ACUITY major bleeding following immediate sheath removal exhibited a dose response with bleeding rates decreasing with increasing levels of reversal. Rates of bleeding were lower in the 75% and 100% reversal arms than heparin. In addition, the incidence of ischemic events was lower in REG1 treated patients compared with those treated with heparin.
Adverse events (AEs) other than bleeding and ischemic events were rare and evenly distributed among the arms of the study. Three patients, clustered late in the trial and in Europe, had allergic-like reactions shortly after receiving pegnivacogin. Characterization of these reactions is ongoing.
"We are thrilled by the results of RADAR and the groundbreaking advance in anticoagulant therapy that they foretell. It is now clear that control matters. REG1 uniquely has shown the promise of simultaneously reducing ischemia and bleeding in comparison to heparin," said Dr. David J. Mazzo, President and CEO of Regado Biosciences, Inc. He added, "The results of the RADAR trial solidly support Phase 3 development of REG1 in the broader ACS population. Regado plans to move forward in this indication as well as in a parallel indication of open heart surgery."
"The Phase 2b RADAR results suggest that high intensity FIXa inhibition with active control may ultimately represent a potential treatment option for addressing both ischemic and bleeding endpoints for patients who require short term anticoagulation in acute care settings," said John H. Alexander, MD, MHS, FACC of the Duke Clinical Research Institute (DCRI) at Duke University Medical Center and Chair of the Steering Committee for the study. "For the first time, we've shown that active control of anticoagulation is possible; the hypothesis that this may lead to better ischemic and bleeding outcomes will no doubt be a focus of the REG1 Phase 3 development program."
"Developing a technology that can selectively control anticoagulation has been considered the 'holy grail' for cardiac intervention," said Roxana Mehran, MD, Professor of Medicine and Director of Interventional Cardiovascular Research and Clinical Trials at the Zena and Michael A. Weiner Cardiovascular Institute at the Mount Sinai School of Medicine. "For years, it's been the goal of cardiologists and surgeons to discover a more targeted method of controlling anticoagulation for patients undergoing ACS procedures, and the Phase 2b RADAR results exhibit significant promise toward this objective."
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