November 25, 2014 – Robert Noveck, MD, PhD, and his co-authors discussed the DCRU’s phase I study of the small-molecule reversal agent.
The DCRU’s work in conducting an early-phase study of a new anticoagulant reversal agent was highlighted in a recent issue of the New England Journal of Medicine.
In an extended letter to the editor, DCRU Medical Director Robert Noveck, MD, PhD, and his co-authors discuss the phase I study of PER977, an investigational drug created by Perosphere, Inc. PER977 is a small-molecule agent created to reverse the effects of edoxaban, a factor Xa inhibitor manufactured by Daiichi Sankyo.
The phase I study, conducted at the DCRU’s early-phase facility, was a double-blinded, placebo-controlled trial comparing PER977 with placebo in 80 healthy patients. Patients received escalating, single intravenous doses of PER977 either alone or after being dosed with edoxaban. The patients who received PER977 after edoxaban had their whole-blood clotting times back to within 10 percent of their normal baseline values within 10 minutes.
The researchers also speculated that PER977 might be effective with other anticoagulants.
“PER977 binds in a similar way to the new oral factor Xa inhibitors, edoxaban, rivaroxaban and apixaban, and to the oral thrombin inhibitor, dabigatran,” the group wrote in the letter.
“In thromboelastographic studies and rat-tail–transection bleeding assays, PER977 has been shown to reverse anticoagulation with each of the new oral agents.”
Phase II studies of PER977 are already in progress, they added.
Major bleeding is a common complication of antithrombotic therapy, and many new anticoagulants have no known reversal agents. An effective reversal agent for these drugs would allow clinicians to regulate their patients’ blood flow more safely and effectively.
In addition to Noveck, the letter’s authors were Jack E. Ansell, MD, of Hofstra North Shore–LIJ School of Medicine; Sasha H. Bakhru, PhD, Bryan E. Laulicht, PhD, Solomon S. Steiner, PhD, and James C. Costin, MD, of Perosphere; and Michael Grosso, MD, Karen Brown, PhD, and Victor Dishy, MD, of Daiichi Sankyo Pharma Development.