Stephan Moll, MD writes… A publication in the New England Journal of Medicine today reports on the use of the Pradaxa® (Dabigatran) antidote Idarucizumab in patients on Pradaxa® who present with major bleeding or require urgent surgery [ref 1].
All patients received the antidote as 2 intravenous bolus injections 15 minutes apart. Primary endpoint was normalization of coagulation tests that are typically prolonged in patients on Pradaxa® – the chromogenic ecarin test (ECT) and dilute thrombin time (dTT). Secondary endpoints were clinical ones: how quickly the bleeding stopped and whether there was more than expected bleeding during the surgery. There was no control group.
The results showed that the antidote was able to completely reverse the anticoagulant effect of Pradaxa® as measured by the coagulation tests mentioned, and that there was not more than expected bleeding in the patients who underwent urgent surgery after the antidote had been given. The drug was well tolerated. The authors’ conclusion is that “Idarucizumab completely reversed the anticoagulant effect of Pradaxa® within minutes”.
The publication presents the data from the first 90 patients treated in the Pradaxa® reversal trial (called RE-VERSE AD; ClinicalTrials.gov identifier: NCT02104947), which aims at eventually enrolling 300 patients. However, the data on these first 90 patients are sufficient for the FDA to review the new drug and approve it within about 6 months, as the drug has been given “accelerated approval status” and “priority review” by the FDA [ref 2,3]. Boerhinger-Ingelheim applied for drug approval in March 2015. Based on the positive results in the present study, the drug is expected to get FDA approval before the end of 2015 and, thus, be available for clinical use by the end of the year. This is, obviously, good news.
Reversal of Other Blood Thinners
A reversal agent (Andexanet) for reversal of the direct oral anti-Xa anticoagulants Xarelto® (Rivaroxaban), Eliquis® (Apixaban), and Savaysa® (Edoxaban) is in development and has just started the key clinical patient trial (called Annexa4; ClinicalTrials.gov identifier: NCT02329327). As this drug also has FDA “accelerated approval status” and “priority review”, the drug will be considered for FDA approval after the first few of the overall anticipated 270 patients in the trial have been enrolled. Andexanet is expected to have enough data from this study to get FDA approval by the middle of 2016 or earlier, if the clinical trial data look good.
- Pollack CV et al. Idarucizumab for dabigatran reversal; N Engl J Med 2015;published June 22, 2015.
- Boehringer-Ingeheim press release: “FDA Grants Priority Review to Boehringer Ingelheim’s Biologics License Application for Idarucizumab”. April 23, 2015 (link here).
- FDA Fast track approval definition (link here)
Last Updated: June 22, 2015