June 20111
Practical considerations :antidote for dabigatran
June 2011Disclaimer: Dabigatran etexilate is only approved for clinical use in stroke prevention in atrial fibrillation in certain countries. Please be aware that there may be national differences between countries regarding specific medical information, including licensed uses, so please check local prescribing information for further details
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)
van Ryn et al. ACC 2011; abstract 1142–367 2
June 2011Disclaimer: Dabigatran etexilate is only approved for clinical use in stroke prevention in atrial fibrillation in certain countries. Please be aware that there may be national differences between countries regarding specific medical information, including licensed uses, so please check local prescribing information for further details
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
van Ryn et al. ACC 2011; abstract 1142–367 3
Kd = dissociation constant; IC50 = half maximal inhibitory concentration
June 2011Disclaimer: Dabigatran etexilate is only approved for clinical use in stroke prevention in atrial fibrillation in certain countries. Please be aware that there may be national differences between countries regarding specific medical information, including licensed uses, so please check local prescribing information for further details
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
4van Ryn et al. ACC 2011; abstract 1142–367
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