Boehringer Says New Bleeding Cases Found in Pradaxa Study

Boehringer Ingelheim GmbH said a new analysis of a company-funded study used to win approval of the blood thinner Pradaxa found 22 serious bleeding events that weren’t included in the original report.

Additional events were found in patients in each of the three arms of the 18,000-patient study known as RE-LY. Five more complications were seen among those taking a 110-milligram dose of the drug, 11 among those on a 150-mg dose and six in the patients using warfarin. Pradaxa became the first alternative to warfarin, the standard of care for more than five decades for preventing strokes caused by blood clots, when it was approved in 2010 by the U.S. Food and Drug Administration.

Boehringer faces more than 2,000 lawsuits involving Pradaxa, a treatment used to prevent strokes in patients who suffer from atrial fibrillation, a heart-rhythm disorder. The Ingelheim, Germany-based company conducted the review after plaintiff’s attorneys uncovered patients who experienced major bleeding and died while taking Pradaxa who weren’t included in the original trial results.

The additional cases don’t change the conclusion that Pradaxa is a safe and effective drug to prevent stroke in patients with erratic heart rhythms, said John Smith, Boehringer’s regional medical director.

“Given the additional review of the RE-LY data, it demonstrates that the original trial results were quite robust,” Smith said in a telephone interview. “The large number of patients per arm makes it relatively insensitive to random human error, which we see when this number of clinical sites and researchers touch a trial.”

Study Authors

The study was led by researchers at the Population Health Research Institute in Hamilton, Ontario. They also conducted the final review of the potentially missed patients identified by 30 Boehringer staff members who combed through 1,500 cases.

Any correction to the original study, which was published in the New England Journal of Medicine in September 2009, would have to come from the researchers, Smith said. If a correction is made, it would be the second to the trial.

The researchers issued a correction in November 2010, saying they identified several additional events when they were conducting “routine clinical site closure visits.” A broader review at the time found 81 more complications, including clots, major bleeding, a stroke and four heart attacks, in 80 patients.

The additional events didn’t materially change the study results and the researchers’ conclusions about the drug’s benefits outweighing the risks remained unchanged, they said at the time.

Bleeding Risk

Patients and their families contend that Boehringer executives knew Pradaxa posed a deadly risk to consumers when it won U.S. approval. More than 1,400 patients bled to death while taking the medicine through Oct. 2, 2013, Andreas Clemens, an executive who oversaw the drug, said in a deposition unsealed Feb. 19 as part of the lawsuits.

The FDA conducted an analysis of Pradaxa use among 134,000 Medicare patients, finding the drug lowered the risk of strokes, bleeding in the brain and death compared with warfarin. Patients getting the Boehringer drug were more likely to suffer major stomach bleeding, while heart attack rates were similar, the agency said yesterday in a safety announcement.

“As a result of our latest findings, we still consider Pradaxa to have a favorable benefit-to-risk profile and have made no changes to the current label or recommendations for use,” the agency said.

The case is In re Pradaxa Products Liability Litigation, 12-MD-02385, U.S. District Court, Southern District of Illinois (East St. Louis).

(An earlier version of this story corrected the number of bleeding incidents involving patients who received warfarin.)

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