OKL-1111, A modified cyclodextrin as a potential universal reversal agent for anticoagulants
The fantastic story of a novel cyclodextrin API.
Antithrombotic therapy is inevitably associated with a risk of bleeding and these bleeding complications can be life-threatening. Recently, specific reversal agents were developed for the direct factor Xa and thrombin inhibitors (DOACs). However, next to the fact that these agents are relatively expensive, the use of selective reversal agents complicates the treatment of bleeding patients in practice. A class of cyclodextrins with procoagulant properties was recently discovered. the lead compound being OKL-1111.
OKL-1111 concentration-dependently reversed the in vitro anticoagulant effects of dabigatran, rivaroxaban, apixaban, and edoxaban in the thrombin generation assay. Also, in the absence of a DOAC, OKL-1111 concentration-dependently accelerated coagulation in this assay but did not initiate coagulation. The reversal effect was also seen for all DOACs in the rat tail cut bleeding model. In addition, when tested with other anticoagulants, OKL-1111 also reversed the anticoagulant effect of the vitamin K antagonist warfarin, the low molecular weight heparin enoxaparin, the pentasaccharide fondaparinux and the platelet inhibitor clopidogrel in vivo. OKL-1111 did not have prothrombotic effects in the Wessler model.
Alveron Pharma – Okklo Life Sciences – Sanquin
Joost Meijers, Kamran Bakhtiari, Alex Zwiers, Stephan Peters