Boehringer Ingelheim withheld Pradaxa data from FDA, lawsuit files show

Drugmakers should clean out their data closets and turn over to regulators every bit of research and analysis they have, according to some healthcare experts. They argue that it is the only way the FDA and others can make informed decisions. Advocates of the tell-all approach are pointing to documents released in litigation against Boehringer Ingelheim, with the company's blockbuster anticoagulant Pradaxa as prime evidence.

Approved in 2010, Pradaxa has been a big seller for the drugmaker. It generated €612 million ($811 million) for the privately held German company in the first half of 2013, a jump of nearly 28%. It was the first approved alternative to warfarin, the standard blood-thinner treatment for lowering cardiovascular risks in some conditions but a product that requires constant monitoring because of its own risks. Studies have indicated Pradaxa has no more bleeding risk than warfarin, but the two ranked first and second on the last list of adverse-event reports. It was Pradaxa's bleeding risks the FDA wanted to evaluate when it sought data from Boehringer Ingelheim.

According to Bloomberg, the documents show that when asked for an analysis of bleeding events tied to the drug, the German drugmaker first provided the FDA one that showed 6.1 patients in 10,000 died from fatal bleeding after it was approved. When asked for data from before approval, the drugmaker turned out two analyses. One showed deaths from bleeding had actually been lower before approval, running 5.8 in 10,000. The second showed that people who had a major bleeding event and died for any reason ran 19.5 in 10,000. The drugmaker gave the FDA all of the underlying data but only the analysis which indicated the risks of bleeding had declined since approval.

Company spokeswoman Marjorie Moeling told Bloomberg that was because Boehringer Ingelheim did not have the same data for analysis in the postapproval group. "The company is completely confident that all of the facts will show that Boehringer Ingelheim acted appropriately and responsibly," she said.

But Harlan Krumholz, a Yale University cardiologist who heads an effort to get companies and researchers to share all their findings, said there is no reason not to provide both reports. "The fact that different analyses of the same data can yield different conclusions makes it imperative that we promote an opportunity for independent analyses through data sharing so that these issues will be out in the open," he told Bloomberg.

The disclosure of the documents comes at a tricky time for Boehringer Ingelheim. The FDA said last month it was going to take yet another look at the bleeding risks for Pradaxa compared to warfarin with a data dive into an electronic healthcare database of more than 100 million patients. Other anticoagulants have come into the market in recent years, like Xarelto from Bayer and Johnson & Johnson ($JNJ) and Eliquis from Pfizer ($PFE) and Bristol-Myers Squibb ($BMY), but the FDA is not including them in its review.

Boehringer Ingelheim recently disclosed that it faces about 2,000 lawsuits accusing it of not being forthright about the severe and fatal bleeding risks it knew Pradaxa presented. Other documents released in the litigation showed marketing managers wanted to downplay a company-produced study showing that the drug would be safer for some patients if their blood levels were routinely monitored. The convenience of not having such monitoring is one of Pradaxa's selling points. The company responded to the disclosures by The New York Times by saying the documents "represent small fragments of the robust discussion and debate that is a vital component in all scientific inquiry."

- read the Bloomberg story
- here's the NYT article (sub. req.)

Editor's Note: An earlier version of this story mis-stated the death rates in one of two Pradaxa studies. It was 19.5 per 10,000, not 19.5% per 10,000.  

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