UPDATED: FDA returns for look at risk of Boehringer Ingelheim's Pradaxa

The sometimes-fatal bleeding risk of Pradaxa, the popular anticoagulant and alternative to warfarin, has been a concern to the FDA since the drug was approved in 2010. FDA and clinical reviews have not found the chances of bleeding to be any greater for the Boehringer Ingelheim drug than for warfarin, but it continues to top the list for adverse reaction reports, and the FDA has decided to do another data dive into how the two compare.

The agency is seeking comment on the protocol for an "assessment of selected safety outcomes in adults with atrial fibrillation who are new users of dabigatran or warfarin." Dabigatran is the generic name for Pradaxa. The review will be done by the agency's Mini-Sentinel program, which monitors the safety of FDA-regulated medical products by assessing electronic healthcare data. It currently can tap a database of more than 100 million patients, points out Forbes blog contributor Larry Husten. 

In an email statement, Boehringer Ingelheim said, "It is important to note that the protocol currently posted on the Mini-Sentinel site states that the fact that FDA requests and receives data on a particular product through Mini-Sentinel does not necessarily mean there is a safety issue with the product. The protocol also provides rationale for the focus of the FDA's assessment on dabigatran, noting that the use of other alternative anticoagulants (e.g., rivaroxaban or apixaban) is "expected to be too uncommon for an adequately powered analysis during the assessment period."

Warfarin is a cumbersome drug. It is difficult to dose, requires ongoing monitoring and comes with significant bleeding risks of its own. It ranked No. 2 last year for adverse events. So the new anticoagulants have found a receptive market. EvaluatePharma's World Preview report last year predicted that the market for anticoagulant drugs will expand by 11.5% annually through 2018, hitting $15.3 billion in sales. That makes it the fastest growing therapeutic area. Pradaxa was the first alternative approved and has been a big seller. It generated €612 million ($811 million) for the privately held German company in the first half of 2013, a jump of nearly 28%. It was followed into the market by other anticoagulants like Xarelto from Bayer and Johnson & Johnson ($JNJ) and Eliquis from Pfizer ($PFE) and Bristol-Myers Squibb ($BMY).

While warfarin is not as easy to use as those alternatives, it possesses an advantage over its competitors when it comes to bleeding risks. It has a quick-acting antidote, vitamin K. Pradaxa, Xarelto and Eliquis have no antidote, although the makers of those drugs are working with partners to develop one.

At this point, the FDA is only looking at the bleeding risks for Pradaxa, Husten notes. And this is not the first time the agency has turned to Sentinel to take a look at the drug. In 2012, FDA staffers reviewed insurance claims and other data from an early version of the safety-monitoring system. That review determined that the bleeding reports for Pradaxa were about the same as those for warfarin. Results of a long-term study of Pradaxa released by Boehringer Ingelheim at the same time confirmed that finding.

- here's the protocol announcement
- more from the Forbes blog post