BMJ targets Pradaxa safety, scolding Boehringer, FDA and EMA alike

Pradaxa is under fire again.

The BMJ has set off a kerfuffle--and a Twitter campaign--over the safety of Boehringer Ingelheim's blockbuster anticoagulant Pradaxa. With three articles and an editorial devoted to the drug in its latest issue, the journal not only advocates regular blood tests for Pradaxa patients, but accuses the company of burying data that would have backed that testing from the get-go.

Meanwhile, the journal doesn't limit its barbs to Boehringer and the drug. It scolds U.S. and European regulators for their oversight, saying that the FDA rushed Pradaxa to market, and both agencies failed to follow up adequately when reports of serious bleeding started pouring in.

Following up on earlier calls for blood-level testing on Pradaxa patients, the BMJ teamed up with the Institute for Safe Medication Practices and the University of Ottawa to probe safety data. They concluded that serious, even fatal bleeding could be reduced by 40% if Pradaxa patients' blood levels were monitored and doses adjusted accordingly.

Problem is, one of Pradaxa's selling points against its older competitor warfarin is that it doesn't require close monitoring and dose tweaking. And the BMJ alleges that Boehringer withheld an internal analysis that advocated the testing, precisely because it wanted to keep that marketing advantage.

Boehringer came out swinging as soon as the BMJ articles hit, accusing the journal of "biased" reporting. The German drugmaker also said that it has already fully addressed "many of the allegations made by BMJ," because they were "reported months ago in the media."

"Our company has provided regulators with the complete data set and analyses of clinical evidence demonstrating Pradaxa's benefits and safety, and FDA and EMA have affirmed RE-LY's conclusions," the company said in a statement. "BMJ was provided this information by Boehringer Ingelheim, but chose not to include it."

And with a story on the debate airing on TV Wednesday in the U.K., the company also took to Twitter to defend itself, issuing a series of tweets via its U.K. handle, PMLive reports. Among them were reminders that the FDA performed its own review of Pradaxa safety, and ended by backing the drug as more effective as warfarin, and safer in most ways.

The BMJ articles do spotlight some previous Pradaxa arguments reported in the media, including FiercePharma. Allegations that Boehringer cherry-picked data, for instance, which surfaced in court fights over Pradaxa patients who died or suffered serious bleeding while using the drug. Boehringer recently agreed to pay $650 million to settle 4,000 of those cases.

The journal says the reporting also depends on BMJ's own research, including data unearthed in U.S. litigation over Pradaxa. Besides advocating testing and questioning Pradaxa's path to approval, the journal chastised the FDA and EMA for failing to require blood tests--despite the fact that they knew plasma levels of the drug varied dramatically.

"Most patients could benefit from a lower dose and reduced bleeding risk with no loss off efficacy," one of the BMJ studies concludes, urging regulators to set an acceptable blood-level range and recommend dose adjustments.

Boehringer maintains that testing isn't needed, and that no diagnostic tool is validated to assess the risk of bleeding in any case. But the company agreed with one point in the BMJ editorial: that doctors and patients need to weigh the risk of bleeding against the reduced risk of stroke. And as one of the study authors notes, the only way to really determine which anticoagulant is safest and/or most effective is to put them all in a head-to-head study.

- read the Medscape story (reg.req.)
- get more from PMLive
- see the MedPage piece

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