Today we will be discussing a new drug called idarucizumab, which was developed to reverse the anticoagulant effects of dabigatran.
Dr. Charles who is leading a multi-center, prospective study of idarucizumab describes dabigatran:
“Dabigatran is a direct oral anticoagulant that works by inhibiting the function of factor IIa, thrombin, and it’s been licensed for the prevention of stroke and systemic embolism in patients with nonvalvular atrial fibrillation and also for the treatment and prevention of venous thromboembolic disease.”
Compared to warfarin, patients taking dabigatran have a lower risk of intracranial hemorrhage, but they are still at risk for major bleeding or may require urgent surgery. However, there are currently no licensed therapeutics for reversal of non-vitamin K oral anticoagulants such as dabigatran.
Idarucizumab is a monoclonal antibody fragment with a high affinity for dabigatran. Preclinical studies have shown that the drug effectively removes the anticoagulant effect of dabigatran, and idarucizumab is now under review in an ongoing, prospective cohort study called RE-VERSE AD (referring to reversal of “active dabigatran”). Dr. Pollack describes the study groups:
“The ones we call Group A are patients taking dabigatran who have serious or life-threatening bleeding and…warrant immediate reversal of the dabigatran effects. The other group, the ones we call group B, are pre-procedural patients who are taking dabigatran and who need an urgent surgical or other invasive procedure. So we’re looking at those two groups receiving a standard dose of 5 grams of idarucizumab.”
Although the study has not been completed, an interim analysis of the first 90 patients, which includes 51 Group A patients who were bleeding and 39 pre-procedural Group B patients, has recently been published in The New England Journal of Medicine. Idarucizumab reversed the anticoagulant effects of dabigatran in all of the patients within 4 hours, and 80% were still reversed 24 hours later. In spite of idarucizumab’s effective removal of dabigatran, there is still a risk of bleeding due to other etiologies, such as damaged blood vessels, concomitant antiplatelet therapy, or other coagulopathy.
Here again is Dr. Pollack.
“The FDA specifically gave idarucizumab this sort of new status called ‘breakthrough therapy’ designation, which means that the FDA is willing to look at data before the phase III trial is even complete because they recognize that this fills a current gap in practice. The FDA and subsequently also the EMA, have given expedited review to idarucizumab.”
We’ll be back again with another edition of Transfusion News on September 15th. Thanks for joining us.
- Pollack CV, Reilly PA, Eikelboom J, Glund S, Verhamme P, Bernstein RA, Dubiel R, Huisman MV, Hylek EM, Kamphuisen PW, Kreuzer J, Levy JH, Sellke FW, Stangier J, Steiner T, Wang B, Kam CW, Weitz JI. Idarucizumab for dabigatran reversal. The New England Journal of Medicine 2015; 373: 511-520.
- Bauer KA. Targeted anti-anticoagulants. The New England Journal of Medicine 2015; 373: 569-571.