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In September the first reversible antithrombotic drug entered phase 3 clinical trials in patients undergoing percutaneous coronary intervention (PCI). The REG1 anticoagulant system developed by Regado Biosciences, of Basking Ridge, New Jersey, is a two-component therapeutic consisting of a nucleic acid aptamer and its control agent. The combined drugs are pegnivacogin (RB006), a single-stranded 31-nucleotide aptamer that binds and inhibits Factor IXa, and a complementary 15-nucleotide control agent anivamersen (RB007). By adjusting the dose of anivamersen, physicians can release the therapeutic pegnivacogin from Factor IXa allowing coagulation activity to resume. Pegnivacogin is pegylated, with a half-life of more than 24 hours, whereas the control agent anivamersen is metabolized in a few minutes.

Doctors administer strong anticoagulants, most commonly heparin or Angiomax (bivalirudin), during PCI procedures. Because these drugs take several hours to metabolize, the arterial sheath—a plastic tube inserted into an artery to access diseased vessels—remains in place for up to six hours after the procedure to minimize the risk of major bleeding from its removal. With REG1, doctors can dial back pegnivacogin's activity immediately and remove the sheath. “We don't have anything like it in cardiology,” says George Dangas, a professor of cardiology at Mt. Sinai Hospital in New York. A reversal agent for heparin exists, but carries significant side effects and no one is eager to use it, Dangas adds. In the phase 2 studies, REG1 was better than heparin at controlling bleeding but there were three severe adverse events in a total of 41 patients treated before the trial was suspended. This turned investors off, says Edward Nash, a biotech analyst at Cowen and Company in New York, although the events were unlikely to be related to the drug. Regado raised only $47 million out of an anticipated $75 million during the company's initial public offering earlier this year. Regado is financing the phase 3 study on its own. The trial will compare REG1 with Angiomax from The Medicines Company, Parsippany, New Jersey, to assess whether the drug is superior in reducing recurrent heart attacks, strokes and the need to revascularize, says David J. Mazzo, CEO. Ritu Baral, a biotech analyst at New York–based Cannacord Genuity rated the company's stock as a 'buy' stating “REG is a highly innovative new anticoagulant that could improve outcomes across a large number of cardiovascular procedures.”