Boehringer Ingelheim: Benefits and Safety of Pradaxa Repeatedly Confirmed
Ridgefield, CT, July 23, 2014 – Boehringer Ingelheim (BI) wants to set the record straight following misleading statements that the British Medical Journal (BMJ) published today regarding Pradaxa® (dabigatran etexilate mesylate). We are concerned that this publication may alarm patients and prompt them to stop taking Pradaxa, thereby increasing their risk of stroke.
To be clear, many of the allegations made by BMJ were reported months ago in the media and have been previously addressed in full by BI.
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 and state that Pradaxa provides an important health benefit when used as directed.
BMJ was provided this information by Boehringer Ingelheim, but chose not to include it.
Contrary to the BMJ’s accusation that BI withheld analyses, here are the facts: in 2012, our scientists performed preliminary, exploratory simulations with mathematical models to understand whether dose adjustments based on plasma concentrations might further improve Pradaxa’s benefits and safety. Because the simulations did not offer reliable predictions of actual patient outcomes, they were not provided to regulators. However, all of the data that was used for the simulations had already been provided.
It is inappropriate to provide regulators simulations that are unreliable and have limitations. Post-hoc exploratory analyses are commonly performed to generate or test hypotheses and are not structured to direct patient management. Thus, they generally are not shared with regulators and first need to be tested in a clinical trial, as many hypotheses, such as the one discussed here, prove to be incorrect.
“Boehringer Ingelheim made a robust effort to find ways to utilize plasma levels to further improve the risk/benefit profile of Pradaxa and it is irrational to suggest otherwise,” said Sabine Luik, M.D., senior vice president, Medicine & Regulatory Affairs, Boehringer Ingelheim Pharmaceuticals, Inc. “The truth is the totality of scientific evidence does not support dosing decisions for Pradaxa based on blood levels. The research shows that individual patient characteristics, such as kidney function and certain medications, are critical factors in contributing to the risk of bleeding.”
We are deeply concerned that the BMJ’s biased reports could compromise the health and safety of people who may benefit from Pradaxa to reduce their risk of thrombotic events.
Further, innuendos that we should have done more than one trial are false. The pivotal RE-LY trial was intensively discussed and agreed to with regulatory authorities. RE-LY included more than 18,000 patients in over 40 countries, and is one of the largest trials ever conducted in non-valvular atrial fibrillation patients to assess stroke risk reduction. Post-market data assessments from FDA reinforce the favorable risk/benefit profile shown in RE-LY.
FDA published a perspective on the findings from a Mini-Sentinel study in the New England Journal of Medicine in 2013. On May 13, 2014, FDA once again reaffirmed Pradaxa’s positive benefit-risk profile when it issued a Drug Safety Communication that included results from a Medicare study comparing new users of Pradaxa and warfarin who had received a diagnosis of atrial fibrillation. This included more than 134,000 Medicare patients, who were 65 years or older. The new study found that, among new users of blood-thinning drugs, PRADAXA was associated with a lower risk of clot-related strokes, bleeding in the brain and death compared to warfarin. The study also found an increased risk of major gastrointestinal bleeding with use of Pradaxa as compared to warfarin, but unlike in RE-LY, no increased risk of MI compared to warfarin.
BMJ also failed to inform its readers that earlier this month, an FDA director authored an article describing atrial fibrillation (AFib), the important role of anticoagulation and novel oral anticoagulants (NOACs) like PRADAXA, rationale behind why the NOACs were approved without an antidote and how the FDA conducts its post-marketing surveillance on all NOACs. The FDA director specifically stated that Pradaxa provides an important health benefit when used as directed.
As with any anticoagulant, there needs to be a balanced consideration of stroke risk reduction and bleeding risk. Patients should not stop taking their anticoagulant medication without first talking to their health care providers. Discontinuing anticoagulation therapy puts a patient at increased risk of stroke.
About Boehringer Ingelheim Pharmaceuticals, Inc.
Boehringer Ingelheim Pharmaceuticals, Inc., based in Ridgefield, CT, is the largest U.S. subsidiary of Boehringer Ingelheim Corporation (Ridgefield, CT) and a member of the Boehringer Ingelheim group of companies.
The Boehringer Ingelheim group is one of the world’s 20 leading pharmaceutical companies. Headquartered in Ingelheim, Germany, it operates globally with 142 affiliates and more than 47,400 employees. Since it was founded in 1885, the family-owned company has been committed to researching, developing, manufacturing and marketing novel medications of high therapeutic value for human and veterinary medicine.
Social responsibility is a central element of Boehringer Ingelheim's culture. Involvement in social projects, caring for employees and their families, and providing equal opportunities for all employees form the foundation of the global operations. Mutual cooperation and respect, as well as environmental protection and sustainability are intrinsic factors in all of Boehringer Ingelheim’s endeavors.
In 2013, Boehringer Ingelheim achieved net sales of about $18.7 billion (14.1 billion euro). R&D expenditure in the Prescription Medicines business corresponds to 19.5% of its net sales.
Source: Boehringer Ingelheim
Posted: July 2014