Wednesday, 29 June 2016

I dare you to Idarucizumab for dabigatran reversal

The major concern over the new oral anticoagulants (NOAC’s) was the lack of a rapid reversal agent. With some pretty clever science comes what many have been waiting for.

This was a randomized double blind placebo controlled trial of 13,429 patients with severe haemorrhagic complications while on dabigatran (Pradaxa). They were randomized to reversal with idarucizumab (Praxbind) or matching placebo. The primary outcome was mortality at 30 days with secondary outcomes of safety and haemorrhage control.

Just kidding... Such a study would never be feasible and some might argue unethical.

Therefore, this was a small unblinded, uncontrolled interim analysis of a larger observational study. As expected, it was sponsored and mostly written by the drug company that stands to make handsome profits if they return positive results.

90 patients on dabigatran who had serious bleeding or required an urgent procedure were given idarucizumab. Most were found to have elevated thrombin or ecarin clotting times at baseline. Evidently, the study drug normalized the test results in 88 to 98% of the patients rather quickly.

So, it seemed to work.

(I’m not going to dwell on the study’s primary outcome measure of “maximum percentage reversal of the anticoagulant effect” as I believe this overstates the real efficacy of idarucizumab. Ok... it was 100% (95% CI 100 to 100). How close were they trying to make the goal post?)

Despite the profound limitations of this study, I will probably give this reversal agent in the rare event I have a suitable patient that meets indications. I think it makes sense.

It is a monoclonal antibody. Unlike activated clotting factors, it is probably safe and unlikely to cause thrombotic events. However we will need to look at phase IV post marketing experience to be sure.

Some quick comments.

This study led to the approval of idarucizumab by the FDA in October 2015 and TGA in June 2016. As of this writing, it is available in some centres in Australia under the Special Access Scheme until Boehringer Ingelheim can get the proper packaging that will satisfy TGA regulations. In a few months it should cost about $3000 a pop.  

Boehringer is probably loving the fact that they can now market dabigatran as having a rapid reversal agent. Cha-ching!

Not to be outdone, the other NOAC’s (rivaroxaban, apixaban) will probably have reversal agents come to market soon (andexonate alfa).

Oh... and the name “idarucizumab?”

Sometimes I wonder if the drug companies purposely make the generic names as confusing as possible so we resort to using the catchy trade names. Sure “Praxbind” is catchy. But so is “I dare you cizumab.” Since two vials are usually given, “I double dare you cizumab!”

Beat that Praxbind!



Covering:

Pollack CV, Reilly PA, Eikelboom J, et al. Idarucizumab for dabigatran reversal. N Engl J Med 2015;373:511-20.



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