Pradaxa Bleeding Risk Info Withheld From FDA, Docs Show

New documents released as part of the ongoing Pradaxa litigation suggest that the makers of the controversial anticoagulant were not wholly forthcoming with government regulators about the science behind the drug, raising even more questions about the approval of Pradaxa and how Boehringer Ingelheim has handled the medication.  

Boehringer Ingelheim currently faces more than 2,000 Pradaxa lawsuits filed by former users of the drug who allege that they experienced uncontrolled bleeding, or that family members bled to death after using the drug.

As part of discovery process in the litigation, records have been released that seem to indicate that Boehringer Ingelheim failed to disclose a data analysis to the FDA that showed an increase in the rate of Pradaxa bleeding deaths after the drug hit the market.

According to a report by Bloomberg News, the drug maker provided data and an analysis to the FDA that indicated the fatal bleeding rate with Pradaxa was less than expected after the drug was introduced in 2010. That analysis was based on an estimated rate of fatal bleeding incidents predicted from clinical trials before the drug was approved, and painted a rosy picture of the drug’s performance.

However, while the company gave the FDA all of the data, it withheld an analysis of the data that reportedly showed the death rate was actually higher, Bloomberg News reports.

Company officials did not deny withholding the analysis, but instead claim they gave the FDA the most appropriate comparison.

Internal Documents Show Questionable Practices

The documents are the latest in a string of revelations that raise serious questions about how Boehringer Ingelheim introduced Pradaxa onto the market.

Pradaxa (dabigatran) was approved in October 2010 as the first of several new blood thinners designed to prevent stroke in patients with atrial fibrillation. The company billed the drug as safer and easier to use than warfarin, also known as Coumadin, which has been on the market for decades. Pradaxa requires less blood tests and monitoring during treatment, and was promoted as being just as effective.

The lawsuits filed over Pradaxa center around the drug makers failure to warn about the bleeding risk and the lack of a reversal agent that could allow doctors to stop hemorrhages that may develop. While the anticoagulant effects of warfarin can be quickly countered with vitamin K, Pradaxa has no approved antidote.

Complaints allege that withholding important safety information about Pradaxa left doctors without a strategy for stopping Pradaxa bleeding events. While some studies have shown that the chances of bleeding may be about the same with the two drugs, evidence continues to emerge highlighting how Pradaxa bleeding problems may pose a more serious risk, since hemorrhages are typically harder to stop.

In recent months, the entire premise for Pradaxa requiring less testing has come into question. Other Boehringer Ingelheim documents released earlier this month suggest that company officials knew that some patients needed more medical monitoring than others, but attempted to cover up the clinical data. The documents showed that the drug maker had clinical data indicating that some patients metabolize Pradaxa differently but urged a company clinical program director to keep those conclusions from the public.

Questions have also been raised about the very clinical trial that led to Pradaxa’s approval. The study, known as RE-LY, was so rife with errors that it alarmed FDA reviewers, who initially rejected Pradaxa and sent the study back, approving it eight months later after the problems appeared to be fixed.

“Although we recognized that there will be some errors in the data sets from large trials, the errors found by relatively unsophisticated means in clinically important data sets during preliminary review called into question the overall quality of those data sets and our confidence in them,” FDA reviewers wrote.

Other researchers from the University of British Columbia looked at RE-LY in 2011 and said Pradaxa should have never been approved, and called for an independent audit of the clinical trial that should look for “irregularities in conduct” as well as sources of bias and questionable data.

Pradaxa Litigation

Since August 2012, the federal Pradaxa litigation has been consolidated as part of an MDL, which is centralized before U.S. District Judge David R. Herndon in the Southern District of Illinois to reduce duplicative discovery, avoid conflicting rulings from different judges and to serve the convenience of the parties, witnesses and the courts. The company also faces Pradaxa lawsuits in state courts in Illinois, California and Connecticut.

Boehringer Ingelheim’s questionable conduct has continued throughout the litigation process. In December 2013, Judge Herndon fined the company nearly $1 million for inappropriately destroying or withholding important documents, saying that the company had acted in “bad faith” during discovery. The judge has indicated that juries may be told about the companies actions and given an instruction about inferences they may take from the company’s failure to maintain documents.

As part of the coordinated management of the cases in the federal court system, Judge Herndon has scheduled a series of early trial dates in the Pradaxa MDL, known as bellwether cases. These trials are set to begin between August 2014 and February 2015, with the outcomes designed to help the parties gauge how juries are likely respond to certain evidence and testimony that may be repeated throughout a large number of cases.