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Practical considerations : antidote for dabigatran

Practical considerations : antidote for dabigatran. Dabigatran antidote: rationale. The ability to reverse anticoagulation is important in patients who: Require emergency procedures Have taken an overdose

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Practical considerations : antidote for dabigatran

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  1. Practical considerations : antidote for dabigatran

  2. Dabigatran antidote: rationale • The ability to reverse anticoagulation is important in patients who: • Require emergency procedures • Have taken an overdose • To address this, monoclonal antibodies designed to neutralize the activity of dabigatran were generated • Engineered to reduce immunogenicity and maintain activity • Lead candidates were tested for their ability to reverse the anticoagulant effect of dabigatran in human plasma in vitro and in rats ex vivo (diluted thrombin time) 2 van Ryn et al. ACC 2011; abstract 1142–367

  3. Dabigatran antidote: results • Antibody clone 22 demonstrated the following properties: • Highly potent and specific binding to dabigatran (Kd 30 pM) • Binding correlated with complete inhibition of dabigatran anticoagulant activity, both in human plasma and whole blood, with an IC50 of 2–5 nM • Complete inhibition of anticoagulant activity of dabigatran in ex vivo studies Kd = dissociation constant; IC50 = half maximal inhibitory concentration 3 van Ryn et al. ACC 2011; abstract 1142–367

  4. Dabigatran antidote: conclusions • The engineered antibody clone 22 showed potent and selective reversal of dabigatran anticoagulation, without affecting normal haemostasis • Clone 22 is currently under further development for use in the clinic • May allow rapid and specific reversal of dabigatran where required in the future 4 van Ryn et al. ACC 2011; abstract 1142–367

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