By Walter Alexander
SAN DIEGO -- March 17, 2015 -- The REG1 Anticoagulation System using pegnivacogin, a reversible factor IXa inhibitor thought to have potential as an anticoagulant for percutaneous coronary interventions (PCIs), caused unacceptable levels of allergic reactions in the phase 3 REGULATE-PCI trial, researchers reported at the 64th Annual Scientific Session of the American College of Cardiology (ACC).
The trial was terminated by the Data Safety Monitoring Board after 10 patients (10/1,605, 0.6%) had serious allergic events with 1 fatality, stated lead investigator Roxana Mehran, MD, The Icahn School of Medicine at Mount Sinai, New York City, New York, speaking here a late-breaking trial presentation on March 15. By comparison, there was 1 nonfatal event (1/1,601, <0.1%) in the bivalirudin control arm.
The REG1 Anti-Coagulation System, Dr. Mehran explained, also includes anivamersen, an agent that quickly reverses the effect of pegnivacogin. In the previous phase 2 RADAR trial, 50% reversal of pegnivacogin by anivamersen allowed early vascular-sheath removal with 30-day outcomes (death, non-fatal myocardial infarction, urgent target-vessel revascularisation or recurrent ischaemia in the target vessel) similar to those of the heparin control arm. In that trial, 2 serious allergic-like reactions occurred shortly after pegnivacogin administration.
The hypothesis for the open-label REGULATE-PCI trial was that near-complete factor IXa inhibition with pegnivacogin would provide a greater reduction in ischaemic events in patients undergoing PCI than would bivalirudin, by virtue of the anticoagulant reversal with anivamersen, without increasing bleeding.
Dr. Mehran and colleagues observed no differences in the patients receiving REG1 compared with bivalirudin in terms of the study’s primary efficacy endpoint of composite all-cause death, myocardial infarction, stroke or urgent revascularisation, with rates of 6.7% in the REG1 arm and 6.4% in the bivalirudin arm 3 days after angioplasty. Efficacy was still comparable at 30 days.
Analysis of the primary safety endpoint of bleeding did not show superiority for the REG1 system over bivalirudin. Patients receiving REG1 had a 0.4% rate of severe or fatal bleeding compared with 0.1% for bivalirudin at Day 3. Moderate-to-severe bleeding was significantly higher in the REG1 group compared with bivalirudin at Day 3 (6.5% vs 4.1%, P = .002) and Day 30 (7.6% versus 4.8%, P = .001).
Conclusions must be considered exploratory regarding safety and efficacy in REG1, Dr. Mehran cautioned, with only about a quarter of the planned endpoint events accrued because of the early termination. Dr. Mehran concluded that the REG1 concept remains promising, and that research is ongoing to determine the exact cause of the allergic reactions.
[Presentation title: A Randomized, Open-Label, Multi-Center, Active-Controlled, Parallel Group Study To Determine the Efficacy and Safety of the REG1 Anticoagulation System Compared to Bivalirudin in Patients Undergoing Percutaneous Coronary Intervention. Abstract 402-12]