The British Medical Journal has published three reports and one editorial criticizing the way Pradaxa (dabigatran) was approved, and is advising drug dosing in the interest of patient safety.
Boehringer Ingelheim’s Pradaxa is prescribed to patients who have nonvalvular atrial fibrillation (AF). The drug was the first new oral anticoagulant to hit the market in an effort to supersede warfarin, an older anticoagulant. One of Pradaxa’s main selling points was that, unlike warfarin, it does not require drug monitoring. The BMJ reports allege that the manufacturer hid information showing that monitoring would significantly benefit the safety profile of the drug in order to maintain this claim.
Concerns about bleeding risks have plagued Pradaxa since it has been on the market. Pradaxa-related bleeding is particularly dangerous because there is no reversal agent, meaning that life-threatening hemorrhages cannot be remedied.
According to the BMJ reports, BI hid evidence from its own analysis showing that patients would have a significantly lower risk of bleeding if they underwent monitoring. Instead of making this information known to regulators, however, the drug maker hid data showing that drug monitoring “has the potential to provide patients an even better efficacy and safety profile than fixed-dose dabigatran and also a better safety and efficacy profile than a matched warfarin group.”
The BMJ reports said there were flaws in the “design and oversight” of the phase 3 trial, RE-LY. The reports also stated that there was “a potentially higher bleeding risk with dabigatran than has been stated” in the trial. The authors criticized the U.S. Food and Drug Administration (FDA) and the European Medicines Agency (EMA), although less severely, for putting Pradaxa on the market through an expedited process or despite incomplete data.
Dr. Deborah Cohen, BMJ editor who authored some of the reports pointed out that “The US agency had concerns over misreporting of events” with Pradaxa and the company’s application for the drug was initially denied.
“The BMJ has learnt that it has taken three reviews of the data [by Boehringer Ingelheim] to calculate the number of major and fatal bleeds among trial participants, and even today there are doubts whether all events have been properly accounted for.” Cohen said.