Effective reversal of Pradaxa® in healthy volunteers

Results from a healthy volunteer study investigating the reversal of the anticoagulant effect of dabigatran etexilate (Pradaxa) by its specific reversal agent idarucizumab have been published recently in The Lancet. The study showed that idarucizumab led to immediate, complete and sustained reversal of the anticoagulant effect of dabigatran etexilate.

The data support the specific reversal agent as a highly targeted treatment option if reversal of the anticoagulant effect is needed, eg. for urgent interventions. Idarucizumab was granted Breakthrough Therapy Designation by the US FDA and has recently been submitted for approval to the FDA, EMA and Health Canada.

In the healthy volunteer study now published in The Lancet, participants first received dabigatran etexilate and then idarucizumab. The specific reversal agent was given two hours after the last dose of dabigatran etexilate, when dabigatran concentrations were at peak levels. After a five-minute infusion of idarucizumab, anticoagulation was immediately reversed back to baseline levels. The reversal effect was sustained for more than 24 hours for all doses of 2g and above. Idarucizumab was well tolerated by the study participants.

Idarucizumab is the recommended International Nonproprietary Name (INN). Idarucizumab is an investigational drug, which has not been approved for clinical use, and further safety and efficacy testing will be required.

“The data now published in The Lancet show in an impressive manner how effective idarucizumab was for reversing Pradaxa® in healthy volunteers”, said Professor Jörg Kreuzer, Vice President Medicine Therapeutic Area Cardiovascular, Boehringer Ingelheim. “Once approved, the availability of a specific reversal agent for a NOAC will be yet another landmark in anticoagulation care.”

dabigatran etexilate, a direct thrombin inhibitor (DTI), was the first widely approved drug in a new generation of direct oral anticoagulants, available to target a high unmet medical need in the prevention and treatment of acute and chronic thromboembolic diseases. Potent antithrombotic effects are achieved with direct thrombin inhibitors by specifically blocking the activity of thrombin, the central enzyme in the process responsible for clot (thrombus) formation. In contrast to vitamin-K antagonists, which variably act via different coagulation factors.