Xarelto, a best-selling anticoagulant made by German drug maker Bayer, is being investigated by the European drug safety agency, Handelsblatt has learned. Xarelto is the second German anticoagulant to come under the scrutiny of European regulators this week.
Medicine to prevent strokes is a lucrative part of the pharmaceutical industry for Bayer, German rival Boehringer Ingelheim and U.S. leader Pfizer, especially since 2011.
The number of prescriptions for the blood thinners has been skyrocketing. Part of the appeal of the new class of medicine is that patients supposedly do not have to submit to regular, costly blood tests to monitor levels of the drug in the body.
Bayer, the maker of Xarelto, and Boehringer Ingelheim, maker of Pradaxa, each generate more than €1 billion ($1.09 billion) annually with their pills.
But both companies’ products are attracting scrutiny.
“We need a new leader at the FDA who is prepared to stand up to the pharmaceutical companies and work to substantially lower drug prices,” said U.S. Senator Bernie Sanders, a Democrat running for president.
“We need a new leader at the FDA who is prepared to stand up to the pharmaceutical companies and work to substantially lower drug prices”
Bayer shares fell as much as 4.6 percent on Wednesday on the Frankfurt Stock Exchange, touching a seven-week low of €110.65. By early afternoon local time, the stock traded down 1.9 percent at €113.80.
On Monday, Handelsblatt reported that a prosecutor in Mainz was investigating allegations that Boehringer Ingelheim deceived the European Medicines Agency about the safety of Pradaxa. The company has vehemently rejected the accusation, saying its tests show the drug is safe.
According to the criminal complaint, Boehringer Ingelheim reportedly didn’t inform the EMA about the dangers of overdosing and under-dosing of Pradaxa when patients do not submit to physican visits and blood testing.
Regular blood tests aim to prevent such dangerous conditions, but the supposed benefit of drugs like Pradaxa and Xarelto is that such physican visits are not required, which lower overall medical costs and make insurers more likely to reimburse physicians who prescribe the drugs.
Bayer is on the defensive because the European regulator is looking closely at Xarelto. Bayer is said to have used a faulty device in the clinical trials that led to the agency’s approval of Xarelto. The U.S. Food and Drug Administration has already taken up the case.
It could escalate into a nightmare for Bayer.
In the United States alone, Bayer faces more than 1,200 lawsuits from patients and relatives who say Xarelto is responsible for health impairments and deaths.
Boehringer and Pfizer are also being sued in connection with their own anticoagulants. All three companies reject the allegations.
The German Federal Institute for Drugs and Medical Devices, which is part of the European regulatory body, says a faulty device was apparently used in clinical trials to measure blood clotting in patients.
“All the authorities are taking it very seriously,” said a spokesperson for the German institute who declined to be named. He stated that the procedure will be examined thoroughly. Patients taking Xarelto shouldn’t stop taking the drug without first talking with their doctor, he said.
The issue could mushroom.
The European regulator plans to check to see if it should question the validity of the results of the clinical trials.
In the so-called Rocket AF clinical trials, the results of Xarelto patients were compared with people who had taken Warafin, an older class of commonly prescribed blood thinner. Bayer needed to show that its drug was at least as good as Warfarin to gain approval.
The German institute has disclosed that the test device was used only for the Warafin control group, since the effect of Bayer’s Xarelto was supposed to be comparable to the competitor’s product without regular blood tests.
Based on the Rocket AF clinical trials, Xarelto was approved in the United States and in Europe in 2011 for stroke prevention in atrial fibrillation.
The test devices in question are hand-held coagulation analyzers that display results of tests to determine how quickly a patient’s blood clots. The longer the clotting occurs in the prescribed therapeutic range, the less the risk of bleeding or stroke.
Bayer says it’s working with health authorities “to clear up possible questions.”
In addition, the company referred to a series of sensitivity analyses that the firm says confirm the results shown in the Rocket AF studies and Xarelto’s positive use-risk profile for patients with atrial fibrillation.
Moreover, the Duke Clinical Research Institute at Duke University in Durham, North Carolina, came to the conclusion that the device didn’t distort test results.
It’s questionable whether the Duke Clinical Research Institute was the best place for this case since Bayer’s Rocket AF clinical trials were once supervised there – and by nobody less than Robert Califf.
U.S. President Barack Obama recently nominated Mr. Califf for the post of FDA commissioner.
Mr. Califf had raised questions about Warafin. “The prevalence of atrial fibrillation is increasing, and many patients who are at risk for stroke are not currently being managed effectively or optimally,” he said.
Moreover, in the hearing for his nomination, many members of Congress accused him of having too close ties with the pharmaceutical industry. He was a consultant for pharmaceutical companies and drew money from the industry for his research institute.
Mr. Califf has been a paid consultant to the pharmaceutical industry for years. His clients included Janssen Pharmaceuticals, which has the license to market Xarelto in the United States.
The U.S. regulator would only say that it’s aware of the issue with the testing device and is exploring the device’s possible influence on the test outcomes.
The agency had serious doubts about the drug in 2011. An FDA advisory panel at first denied approval but then gave the green light. Back then, irregularities in the control group had been noticed.
Mr. Califf, 64, is one of the most-quoted heart specialists in the United States. Despite his ties to the pharmaceutical industry, he could get the top job at the U.S. regulatory agency. The Senate’s decision is expected in the coming weeks.