Ciraparantag (PER977): Broad-Spectrum Anticoagulant Reversal Agent

Ciraparantag is an intravenously administered synthetic molecule designed by Perosphere as a broad-spectrum reversal agent for anticoagulants.  

Anticoagulants are widely used for the prevention and treatment of a variety of thromboembolic events. While new oral anticoagulants (NOACs) exhibit predictable anticoagulant action and improved side effect profiles, they lack a broad-spectrum reversal agent. Pharmacologic anticoagulation becomes a clinical problem when anticoagulated patients experience major bleeding, have a traumatic injury, or require emergency surgery -- which is the clinical motivation for developing a broad-spectrum reversal agent for anticoagulants.

Annually, millions of patients in the United States require anticoagulation. The new oral anticoagulant (NOAC) factor Xa or IIa inhibitors have numerous advantages: rapid therapeutic effectiveness, ease of dosing, and lack of monitoring requirements. However, increased risk of major bleeding in cases of overdose, trauma, or emergency surgery remain a significant issue as does the need for temporary discontinuation in the event of an elective invasive procedure.

Currently there is no approved broad-spectrum reversal agent for the NOACs or for low molecular weight heparin. A broad-spectrum anticoagulant reversal agent would allow for rapid emergency response to overdose or trauma, minimize the time patients are off their anticoagulant prior to elective procedures, and provide a level of confidence regarding restarting anticoagulant therapy. 

Ciraparantag, is an intravenously administered synthetic, small molecule invented by Perosphere for use as a broad-spectrum reversal agent for anticoagulants including low molecular weight heparin (LMWH), unfractionated heparin (UFH) and the new oral anticoagulants (NOACs). The NOACs include Daiichi Sankyo Co., Ltd.'s Savaysa™/Lixiana® (edoxaban), Boehringer Ingelheim GmbH's Pradaxa® (dabigatran), Johnson & Johnson's and Bayer HealthCare AG's Xarelto® (rivaroxaban), and Bristol-Myers Squibb Company's and Pfizer Inc.'s Eliquis® (apixaban).

Currently in Phase 2 clinical trials, ciraparantag has demonstrated that a single bolus i.v. injection produces complete and sustained reversal of Daiichi Sankyo’s SavaysaTM/Lixiana® (edoxaban) and Sanofi’s Lovenox® (enoxaparin sodium injection) without rebound anticoagulation. Furthermore, no pro-coagulant signal has been observed, as measured by D-dimer, F1.2, TFPI or whole blood clotting time in clinical trials. Non-clinical studies have demonstrated reversal of all approved NOACs including Daiichi Sankyo's SavaysaTM/Lixiana® (edoxaban), Boehringer Ingelheim's Pradaxa® (dabigatran etexilate), Johnson & Johnson and Bayer's Xarelto® (rivaroxaban), and Bristol-Myers Squibb and Pfizer's Eliquis® (apixaban).

If PER977 is shown to be safe and efficacious in humans, it would address the completely unmet clinical need for a broad-spectrum NOAC reversal agent and may provide an improved reversal drug for UFH and a complete reversal agent for LMWH, for which protamine is only partially successful.