Boehringer's "gross inadequacy"

Boehringer Fined $931,000 Over Lost Pradaxa Files

Boehringer Ingelheim GmbH, which markets and manufactures Pradaxa, has been charged with a nearly $1 million fine, according to a recent ruling. The fine was levied for the drug maker’s withholding or failing to preserve files sought in Pradaxa litigation, according to the judge’s ruling.

The “countless” files were sought by patients who have brought lawsuits over the blood thinner, Pradaxa, Bloomberg News reports. U.S. District Judge David Herndon, located in East St. Louis, Illinois, is overseeing more than 1,700 consolidated lawsuits that have been filed over allegations that Pradaxa caused excessive and, in some cases, fatal bleeds. Judge Herndon concluded that Boehringer executives acted “in bad faith” when they neglected to ensure that the documents and files in question, which involved the development and marketing of Pradaxa, were preserved.

“The wrongs here are egregious,” Judge Herndon said in the ruling. “The gross inadequacy” of the company’s efforts to protect the documents warranted a sanction of more than $931,000 against Boehringer, the judge added, according toBloomberg News. Boehringer is preparing for the first federal court trial filed over allegations that it hid bleeding risks associated with Pradaxa. The first consolidated case was set by Judge Herndon for trial in August; other cases remain pending in Delaware, California, and Illinois, Bloomberg News reports.

“Boehringer Ingelheim has acknowledged that we have had unintentional and unexpected problems with discovery in this litigation,” Mary Lewis, a spokeswoman for the drug maker, wrote in an emailed statement, according to Bloomberg News.Meanwhile, patients and their families allege that Boehringer executives were aware that Pradaxa posed deadly risks to some consumers when the drug was released to the United States market October 2010, writes Bloomberg News. Pradaxa is unlike other blood thinners because there is no antidote to its effects, which can lead to deadly bleeding events.

For some 50 years, the anticoagulant, Coumadin (warfarin), has been prescribed to patients diagnosed with atrial fibrillation (AF), an irregularity of the heartbeat. The drug is also prescribed to people at increased risk for developing potentially fatal blood clots.

The blood thinner, Pradaxa, is used to reduce risks of stroke and blood clots in patients with non-valvular AF, which is a common heart rhythm abnormality. Pradaxa is not cleared for use in patients diagnosed with AF caused by heart valve problems. The drug inhibits thrombin, which is, according to News-Medical, the central coagulation activator in the body’s blood clotting system.

While Pradaxa and warfarin can both cause internal bleeding, there are antidotes readily available for warfarin bleeds. Mounting Pradaxa bleeding lawsuits allege the drug caused serious, uncontrollable bleeding side effects such GI bleeding and cerebral hemorrhaging for which there is no possible reversal or reversal agent.

Plaintiffs’ attorneys allege that Boehringer officials marketed the drug as better than other blood thinners, yet were aware that Pradaxa was no better than similar drugs. Meanwhile, Pradaxa has been tied more than 500 deaths in the U.S. over a two-year period and, U.S .Food and Drug Administration (FDA) officials say, Pradaxa has been involved in 542 reports of fatalities and 3,781 side-effect incidents in 2011.

Boehringer executives must either provide the files sought by plaintiffs’ attorneys that are in their possession or officially advise the court that they are “unable to comply with the order,” Judge Herndon said. He also said he may consider additional sanctions over the missing files, according to Bloomberg News.

http://www.newsinferno.com/boehringer-fined-931000-over-lost-pradaxa-files/?

Is Pradaxa Worth the Risks? | NewsInferno

Pradaxa, a new type of blood thinner approved by U.S. regulators in October 2011, may not be living up to its promise. According to a report from The Cleveland Plain Dealer, at least one study published this year has linked Pradaxa to a higher risk of heart attacks. Meanwhile, concerns are mounting about Pradaxa’s bleeding side effects, which are often irreversible.

Pradaxa is used to prevent strokes in people with atrial fibrillation. It was expected to be adopted as a replacement for warfarin, which can have dangerous interactions with certain foods. According to the Plain Dealer, warfarin also requires frequent blood tests to monitor how well the blood is clotting.

Pradaxa was approved by the U.S. Food & Drug Administration (FDA) based on the results of the RE-LY trial, which showed it was effective in preventing strokes, but also hinted at a possible risk of heart attacks linked to Pradaxa, according to The Plain Dealer. In January, a study published in the Archives of Internal Medicine, which pooled data for six smaller trials, found that patients in the Pradaxa groups had a 33 percent increased chance of having a heart attack. Overall, there were 237 coronary events among the 20,000 combined trial participants taking Pradaxa compared with 83 of 10,514 taking warfarin, the Plain Dealer said.

Another problem with Pradaxa is bleeding, a common side effect of all blood thinners, including warfarin. Warfarin bleeding can be stopped with the administration of vitamin K, but there is no similar antidote or Pradaxa bleeding. Earlier this month, a study in the Journal of Neurosurgery highlighted this risk, detailing the worsening condition, and ultimate death, of an 83-year-old Pradaxa patient following a minor fall. Within two hours of his arrival at the hospital, scans showed extensive progression of brain hemorrhaging. His doctors administered intravenous fluids and a protein called recombinant factor VIIa to stop the bleed, but nothing worked. The man fell into a deep coma, and died shortly after.

That incident was just latest report to raise concerns about Pradaxa bleeding side effects. Last year, Boehringer Ingelheim acknowledged that since March 2008, it had received 260 reports of bleeding-related deaths in patients taking Pradaxa. The FDA launched a review of Pradaxa in December over reports of bleeding-related side effects, while regulators in Europe and Japan have also directed Boehringer Ingelheim to strengthen warnings for the Pradaxa.

“What we’ve seen is that the amount of people having death from hemorrhagic events in the brain is higher than expected,” epidemiologist Adrian Hernandez told the Plain Dealer. “That’s another part that’s being played out now as part of this risk-benefit.”

via newsinferno.com

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Boehringer Kept Pradaxa Analysis From FDA, Records Show

Boehringer Ingelheim GmbH didn’t disclose a data analysis to U.S. regulators that indicated the blood-thinner Pradaxa may have caused more fatal bleeding after it was cleared for sale than the drug did in a study used to win approval, unsealed court filings show.

Boehringer gave U.S. regulators one analysis of data gathered after the drug’s October 2010 approval that showed the number of people who died from bleeding was less than expected, according to internal documents made public in lawsuits over the product. The company didn’t share a second analysis showing a higher death rate, the documents show.

The Food and Drug Administration was reviewing the bleeding as part of a safety check spurred by results seen in adverse incident reports sent to the agency. Andreas Clemens, an executive who oversees Pradaxa, acknowledged the Ingelheim, Germany-based company shared only one of the analyses and said he couldn’t say why, according to the unsealed court filings.

“Having run an analysis in several ways, there is no good reason not to disclose all the results,” said Harlan Krumholz, a Yale University cardiologist in New Haven,Connecticut, who is leading an effort to get companies and researchers to share their findings fully.

Boehringer gave the FDA the underlying data and provided an analysis using what the drugmaker considered to be the most appropriate comparison, said Marjorie Moeling, a company spokeswoman, in an e-mailed response to questions. “The company is completely confident that all of the facts will show that Boehringer Ingelheim acted appropriately and responsibly.”

2,000 Lawsuits

A company filing this month said Boehringer faces more than 2,000 suits involving Pradaxa, a treatment used to prevent strokes in patients who suffer from atrial fibrillation, a heart-rhythm disorder. Regulators cleared the drug, which generated $1.4 billion in 2012 sales, as the first alternative to warfarin, a product sold by Bristol-Myers Squibb Co. under the brand name Coumadin that’s been used for 50 years to avert strokes caused by blood clots.

Patient lawsuits contend Boehringer knew the drug posed a deadly risk when it won FDA approval. While warfarin offers a way to counteract excessive bleeding, there’s no approved antidote available yet for those on Pradaxa. In November, the company released data from the first human study of an antidote in 145 healthy volunteers.

Boehringer’s decision to provide only one analysis on Pradaxa’s use after the drug’s approval may complicate the company’s defense as it prepares to face the first trial of claims that it hid the medication’s health risks.

‘Selective Presentation’

“It is important to resist selective presentation of results, especially when the finding depends on which analysis is done,” said Krumholz, who isn’t involved in any of the Pradaxa lawsuits, by telephone. “The fact that different analyses of the same data can yield different conclusions makes it imperative that we promote an opportunity for independent analyses through data sharing so that these issues will be out in the open.”

In the Pradaxa case, the regulators asked Boehringer to compare fatal bleeding reports received by the FDA against the number of patients using the drug in order to establish a death rate. The request was made to allow the FDA to “evaluate the need for modifications to the Pradaxa label or future study,” according to a letter made public as part of the court files.

The company reported back that 6.1 of every 10,000 patients who used the drug after approval developed fatal bleeding, the court documents showed. The regulators also asked Boehringer to reanalyze results from an earlier study used to gain approval to see how that rate compared.

Separate Analyses

That effort produced two separate analyses by the company, according to the unsealed court documents. One, looking only at people whose primary cause of death was bleeding, found 5.8 of 10,000 patients died per year. The other, which included anyone who had a major bleeding event and died for any reason, found a rate of 19.5 fatal events per 10,000 patients per year, the documents show.

The report sent to the FDA, though, contained only the analysis indicating the death rate from the earlier research was much higher than the numbers seen after approval, according to the court filings. Potentially, such a finding could head off any after-market action by the FDA because the data showed the drug was safer after it was approved and widely used.

Boehringer’s Clemens, mentioned in the e-mails including in the court documents as one of the executives who decided what information to give the FDA, said it would have been possible to provide both numbers.

‘Number Quality’

He said that Boehringer’s decision to withhold the analysis showing the lower bleeding rate in the pre-approval research may have been driven by concerns about the “quality of this number,” according to the filings.

Moeling, the Boehringer spokeswoman, said the 5.8 per 10,000 number wasn’t an appropriate comparison because it reflected a limited number of cases where doctors determined the bleed was the primary cause of death. Because reports to the FDA aren’t always complete, the company wasn’t able to identify the same specific subgroup after the drug’s approval, she said.

The FDA, meanwhile, hasn’t identified any unrecognized risk factors for bleeding with Pradaxa, said Sandy Walsh, an agency spokeswoman, in an e-mail. The FDA, though, is continuing to evaluate “multiple sources of data in an ongoing safety review,” according to Walsh, who declined to comment on the pending litigation.

Safety Signal

Selective disclosure of Pradaxa information may have camouflaged a serious safety signal, according to an assessment report from European Medicines Agency’s Committee for Medicinal Products for Human Use in August 2012. That agency is the European Union’s drug regulator, equivalent of the U.S. FDA.

“If the reporting rate in the post-marketing phase had been higher than in” Boehringer’s study, “there would clearly have been a safety concern,” agency officials wrote. European drug regulators have Pradaxa under review and American regulators are planning another assessment of the drug’s safety as part of its program to monitor FDA-regulated products.

Boehringer’s conduct regarding Pradaxa may also have a negative impact on future requests for regulatory approvals, said Erik Gordon, a University of Michiganbusiness and law professor who teaches classes about how drugs are developed and regulated in the U.S.

‘Forthright’ Companies

“These are the kinds of drug-company actions that can drive a stake through the heart of an FDA approval process that is based on the idea that companies will be forthright with the data about their products,” Gordon said.

If drugmakers are allowed to continue to select the safety information they share with regulators, consumers can’t be sure the disclosures aren’t being driven by financial concerns, Gordon said in a telephone interview.

This case “should raise some eyebrows,” he said.

Pradaxa suits filed against Boehringer in federal courts across the country have been consolidated for pretrial information exchanges before U.S. District Judge David Herndon in East St. Louis, Illinois. Other cases have been filed in state courts in Delaware, California, Illinois and Connecticut.

Herndon set the first case for trial among the consolidated federal suits for August, according to court dockets. He also ordered Boehringer to pay almost $1 million in fines for withholding or failing to preserve files about the drug’s development and marketing.

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

http://www.bloomberg.com/news/2014-02-25/boehringer-kept-pradaxa-analysis-from-fda-records-show.html?

Clot Wars contd. - More than 2,000 Lawsuits Over Pradaxa Bleeding Risks, Boehringer Confirms

Boehringer Ingelheim, manufacturer of the blood-thinner Pradaxa (dabigatran), has confirmed that it faces more 2,000 lawsuits in the United States alleging that the drug causes severe and fatal bleeding.
The company’s confirmation came after the German newspaper Handelsblatt reported the number. Boehringer said that the company has to weigh the risk of known side effects against the drug’s life saving potential, according to Reuters. “We are certain that we can show in the legal cases that we have worked very carefully and responsibly in research, development and marketing of Pradaxa,” the German drug maker said in a written statement.
Pradaxa is one of a trio of new drugs – along with Xarelto (rivaroxaban), and Eliquis (apixaban) – competing to replace warfarin, a blood thinner in use since the 1950s to prevent strokes in patients suffering from atrial fibrillation, a form of irregular heartbeat common especially among the elderly. While cutting the risk of fatal or debilitating strokes, blood thinners increase the risk of internal bleeding, which can also prove fatal, according to Reuters.
Boehringer’s statement cited a recent study by the U.S. Food and Drug Administration (FDA) as showing that Pradaxa users ran a lower risk of severe bleeding than patients on warfarin, according to Reuters. The New York Times reports that since approval Pradaxa has been prescribed to 850,000 patients, but has also been linked to more than a thousand deaths. According to the Times, Pradaxa sales in 2012 totaled $1.5 billion.
Two weeks ago a federal judge unsealed documents revealing that Boehringer Ingelheim tried to quash an internal study for fear it would damage Pradaxa sales. Judge David Herndon, who released the documents, oversees many of the lawsuits alleging that the drug maker failed to properly warn about Pradaxa’s risks. A key point in Pradaxa’s marketing is that users are not subject to the inconvenience of regular blood tests, as warfarin users are. But the study findings suggested that many Pradaxa users do in fact need blood testing because metabolic differences, especially in older patients, may result in the individual having too little or too much of the drug in their bloodstream, meaning that the patient could be inadequately protected or face increased bleeding risks. This conclusion alarmed Boehringer executives and led to pressure to revise the paper or suppress it altogether.

http://www.newsinferno.com/more-than-2000-lawsuits-over-pradaxa-bleeding-risks-boehringer-confirms/?

Tales From the PMPCA contd. - The Case of the Disparaged Rat Poison

A GP complained that a number of articles about Boehringer Ingelheim’s product Pradaxa (dabigatran) which appeared in the Daily Mail, The Telegraph and the Express on 5 April 2011, referred to the use of the medicine to prevent stroke, an unlicensed indication.  

Pradaxa was indicated for the primary prevention of venous thromboembolic events in adults who had undergone elective total hip or knee replacement surgery.  Boehringer Ingelheim had made an application to the European Medicines Agency (EMA) to extend the licence to prevention of stroke and systemic embolism in atrial fibrillation.

The complainant was concerned that the articles contained exaggerated claims about Pradaxa which had arisen from misleading press releases issued by Boehringer Ingelheim. The coverage contained quotations from UK experts and patient group representatives and it was likely that Boehringer Ingelheim had facilitated access to these individuals and approved this unlicensed promotion of Pradaxa within the UK.

The claims for stroke prevention were based on a retrospective subanalysis of the Randomized Evaluation of Long-Term Anti-coagulant Therapy (RE-LY) study (Connolly et al 2009), which compared the effect of Pradaxa with warfarin in preventing strokes in people with atrial fibrillation.   The complainant noted that this promotion took place after an application was made to the EMA to extend the licence of Pradaxa for the prevention of thromboembolism and stroke in people with atrial fibrillation and the recent approval by the Food and Drug Administration (FDA) for the same.

The complainant also alleged that the press articles disparaged warfarin, a current option, referring to it as a rat poison.   The complainant noted that packs of Pradaxa were also pictured.

The complainant alleged that the promotion to the public of an unlicensed indication was irresponsible and would encourage the public to seek the prescription of Pradaxa for this purpose.

The detailed response from Boehringer Ingelheim is given below.

The Panel noted that the Code prohibited the advertising of prescription only medicines to the public.  However, the Code permitted information about prescription only medicines to be supplied directly or indirectly to the public but such information had to be factual and presented in a balanced way.  It must not raise unfounded hopes of successful treatment or be misleading with respect to the safety of the product.  Statements must not be made for the purpose of encouraging members of the public to ask their health professional to prescribe a specific prescription only medicine.  Complaints about articles in the press were judged on the information provided by the pharmaceutical company or its agent to the journalist and not on the content of the article itself.

The Panel noted that Boehringer Ingelheim had engaged as spokespeople two health professionals and two patient organisation representatives.  At least one of the health professionals was briefed by Boehringer Ingelheim’s media agency, and the company had facilitated the availability of the spokespersons for interviews.  The Panel considered that Boehringer Ingelheim was responsible under the Code for comments made by these spokespersons.  Companies could not use independent experts as a means of avoiding the restrictions in the Code.  The Panel noted that the contract between Boehringer Ingelheim and one health professional spokesperson referred to some of the requirements of the Code, but did not refer either to the prohibition on the promotion of prescription only medicines to the public or the Code requirements on the content of information directed at the public.  The Panel considered that this was a significant omission particularly as the press release was aimed at the consumer press.

The Panel noted that the health professional spokesperson briefed by Boehringer Ingelheim’s media agency was quoted in the press release issued by Boehringer Ingelheim to the consumer press and that some of the press articles included further quotes from him and other spokespersons.  The Panel was concerned that this health professional spokesperson was quoted in The Telegraph article describing Pradaxa as preventing ‘clots better than warfarin but with less bleeding which is pretty much the holy grail for such drugs’.  

The Panel noted that the press release discussed the comparative data in relation to stroke prevention from Flaker et al (2011) a sub-group analysis of the RE-LY study, Connelly et al (2009) the RE-LY study and Connelly et al (2010a) newly identified events in the RE-LY study.  The press release included quotations from the same health professional which described Pradaxa as an ‘invaluable option’ for patients.  The press release did not include the pack shot.
 
The press release stated that, compared to well-controlled warfarin, 150mg dabigatran twice daily showed a 39% reduction in the risk of stroke in patients with paroxysmal atrial fibrillation, 36% reduction in the risk of stroke in patients with persistent atrial fibrillation and a 30% reduction in the risk of stroke in patients with permanent atrial fibrillation. There was no mention of major haemorrhage or any other adverse event in the press release. The Panel noted that Pradaxa was not authorized for use in atrial fibrillation.  The Panel questioned whether in the absence of information in the consumer press release about side effects the press release was balanced.

The Panel noted that the press release mentioned warfarin solely in relation to its use as a comparator in Flaker et al and the RE-LY studies.  It did not refer to warfarin as rat poison and otherwise made no disparaging remarks about the medicine.  The Panel had no evidence about how warfarin had been described by Boehringer Ingelheim’s spokespersons or at any press conference.  No breach of the Code was ruled in that regard.

The Panel was concerned about the very positive statements in the ‘Notes to Editors’ section of the press release which described Pradaxa as ‘leading the way in new oral anticoagulants/direct thrombin inhibitors …targeting a high unmet medical need’ and queried whether this was a fair reflection of the evidence.  The press release did not refer to Pradaxa as a ‘super pill’ or as a ‘revolutionary drug’.  These phrases only appeared in the press articles.

Overall the Panel was very concerned about the content of the press release and the briefing material for spokespersons.  The Panel considered that these would in effect encourage members of the public to ask their health professional to prescribe a specific prescription only medicine.  The Panel was concerned about the lack of information in a consumer press release relating to side effects.  A breach of the Code was ruled.  The press release advertised a prescription only medicine to the public for an unlicensed indication.  The Panel ruled a breach of the Code in that regard.  The Panel considered that promotion of Pradaxa for an unlicensed indication was inconsistent with the terms of its marketing authorization.  A further breach of the Code was ruled.

The Panel considered that high standards had not been maintained and ruled a breach of the Code.  The material promoted a prescription only medicine to the public in an indication that was not yet licensed.  The Panel noted that promotion prior to the grant of a marketing authorization was listed as an example of an activity that was likely to be in breach of Clause 2.  Overall the Panel considered that the press release and the material for spokespersons brought discredit upon, and reduced confidence in, the industry.  A breach of Clause 2 was ruled.

via pmcpa.org.uk

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Pradaxa Maker Reaches $650 Million Settlement in State and Federal Litigation

Drug maker Boehringer Ingelheim announced today that it had reached a $650 million settlement of state and federal cases involving the blood thinner Pradaxa (dabigatran).

Though the company says it “stands resolutely behind” Pradaxa and believes the claims in the lawsuits lack merit, a company news release says the settlement allows BI to avoid the “distraction and uncertainty of lengthy litigation,” according to Insurancenewsnet.com.

This settlement is expected to resolve about 4,000 claims and Boehringer Ingelheim reportedly expects most, if not all, plaintiffs to accept the settlement, Insurancenewsnet reports. The company says Pradaxa is superior to the older blood thinner warfarin in reducing ischemic strokes, while having a similar rate of major bleeding events. Ischemic strokes account for nearly nine out of every 10 strokes caused by atrial fibrillation, a heart rhythm problem.

On May 13, the Food and Drug Administration (FDA) issued a Drug Safety Communication with results from a Medicare study that compared new users of Pradaxa and warfarin. The FDA reports that Pradaxa was associated with a lower risk of clot-related strokes, bleeding in the brain, and death compared to warfarin, but Pradaxa had an increased risk of major gastrointestinal bleeding, according to Insurancenewsnet.com. Vitamin K is an antidote to warfarin bleeding, but there is no antidote for bleeding with Pradaxa, making such bleeding very dangerous.
Pradaxa belongs to a new class of blood thinners, drugs developed to replace warfarin, which has been prescribed for more than 50 years. While blood thinners reduce the rate of fatal or debilitating strokes, they increase the risk of internal bleeding, which can be fatal, Reuters reports. The new blood thinners have been successful in the market because, thus far, patients using them have not needed the regular blood testing and dietary restrictions necessary with warfarin. But The New York Times reports that new studies suggest that Pradaxa users may need blood testing because individuals’ metabolic differences can leave then with too little or too much of the drug in their bloodstream. Too little diminishes the drug’s effectiveness in preventing strokes and too much increases the bleeding risk.

http://www.newsinferno.com/pradaxa-maker-reaches-650-million-settlement-in-state-and-federal-litigation/?

Clot Wars contd. - Boehringer says about 260 deaths related to Pradaxa | Reuters

Nov 12 (Reuters) - Boehringer Ingelheim said that 260 cases of fatal bleeding have been linked to its new stroke prevention pill Pradaxa so far, adding that the risk of death was still below the rate that emerged in the clinical trial that led to the drug's approval.

In early November, the German drugmaker had said that 50 reported deaths were a "reasonable order of magnitude".

The company on Saturday confirmed in a statement the new global number more than five times higher than the previous one, initially reported by magazines Der Spiegel and Die Zeit.

Like other anti-blood-clotting treatments, Pradaxa's benefit of cutting the rate of fatal or debilitating strokes comes at the risk of internal bleeding, which can also cost lives.

Unlisted Boehringer also said there have been fewer cases of fatal side effects linked to Pradaxa than what would have been expected if they had been treated by the standard drug warfarin, which Boehringer is trying to replace.

Warfarin has been used for decades but it is difficult to handle because it interacts with certain vegetables and requires frequent blood tests.

Pradaxa, the first in a promising new class of medicines to overcome these drawbacks, is designed to prevent strokes in patients suffering from atrial fibrillation, a form of irregular heartbeat common among the elderly.

Boehringer said in its statement that the risk of deadly bleeding linked to warfarin was more than 40 percent higher than that associated with Pradaxa, citing figures from the RE-LY study that led to the new pill's approval.

Still, some healthcare watchdogs' attention has been heightened.

European regulators last month said that patients about to take Pradaxa should have their kidneys checked, and Japanese regulators told Boehringer in August to issue a strong warning to doctors of potentially deadly bleeding as a result of use of Pradaxa.

Rival anti-clotting drugs include Xarelto from Bayer and Johnson & Johnson, Eliquis from Bristol-Myers Squibb and Pfizer, and Daiichi Sankyo's Lixiana.

The are all vying for a market that analysts estimate at somewhere between $10 billion and $20 billion per year.

Pradaxa won regulatory clearance in the United States for stroke prevention in October 2010, followed by other important markets this year.

Bayer and Johnson & Johnson's Xarelto could make major gains this weekend at the annual American Heart Association meeting in Orlando, where more clinical data is due to be release.

via reuters.com

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Top of the Pops

Investigation: Pradaxa most complained about U.S. drug; blamed for deaths, life-threatening injuries

CLEVELAND - A Five On Your Side Investigation found Pradaxa, a popular blood thinner,  is the most complained about drug in the United States.

Our research found more complaints were filed with the FDA about Pradaxa than any other prescription drug in both 2011 and 2012.

Since it was approved by the FDA in 2010, Pradaxa has been blamed for 1,158 U.S. deaths and 12,494 serious injuries, according to Tom Moore, the senior scientist for drug safety and policy at the Institute for Safe Medication Practices. The ISMP is a non-profit organization that monitors FDA reports.

The drug is used to treat atrial fibrillation, a heart condition that significantly increases the risk of stroke.

"We've found that this drug had a potential benefit in preventing stroke, but it also had extremely high risk of bleeding as do some other anti-coagulants,” said Moore.

Court Order Reveals Hidden Documents

Earlier this month, as the result of an Illinois court order, documents were released that revealed the drug’s manufacturer, Boehringer Ingelheim, performed a study that showed a small minority of patients could have a higher bleeding risk.

The documents also show the German based company knew regular blood tests could help manage the bleeding risk.

However, in an internal e-mail obtained by 5 On Your Side Investigators, a supervisor expressed concern requiring monitoring could hurt sales.

Dr. Jutta Heinrich-Nols writes “Is it really wanted to publish this?” and “This will make any defense of no monitoring . . . extremely difficult . . . and undermine our efforts to compete (with other blood thinners.)”

The FDA approved with no requirement for regular monitoring.

"It's a great tragedy in medicine in the regulation of drugs,” said Moore.

"There was an opportunity to make it safer, instead it appears the commercial instincts to sell more drugs won out,” he said.

“This drug now needs to be reassessed and it's not clear that it is safe,” he said.

Northeast Ohio Patient Discuss Injuries

Inez Brest, 71, agrees. The Amherst grandmorther suffered a severe cerebral hemorrhage last April after taking Pradaxa a few months.

 "All of a sudden, I had this huge, like it sounded like it went ‘Pow!’ It was like my brain exploded, she said.

“My head was on fire. It was a real god awful feeling. It was like it was burning in there,” said Brest.

Brest now uses a walker and has significant memory loss. “I miss my brain,” she said.

Michael Timko, 67, of Lorain also blames Pradaxa for his injuries.

He has become homebound after experiencing a gastrointestinal hemorrhage in April 2012.

"Even my worst enemy, i wouldn't want to put them in the position I'm in right now,” he said

His wife, Jean, said her husband is completely dependent on her and their daughter.

"He can't take our grandson fishing, that's the one thing he's talked about. He'd love to take Mikey fishing and he can't take Mikey fishing,” she said.

"He doesn't deserve the life he's living now,"  she said.

Brest and Timko are among 2,304 former Pradaxa users who have filed lawsuits in federal court against Boehringer Ingelheim for failing to warn them.

http://www.newsnet5.com/news/local-news/investigations/investigation-pradaxa-most-complained-about-us-drug-blamed-for-deaths-life-threatening-injuries?

Boehringer's Pradaxa advertising breaches Code | InPharm

via inpharm.com

Boehringer Ingelheim has fallen foul of the ABPI Code of Practice on five counts in a row over an advertisement for its anti-stroke pill Pradaxa.

The breaches – adjudged by Code watchdog the PMCPA - all come under clause 7, which deals with information, claims and comparisons.

A GP complained that the advertising for Pradaxa (dabigatran) included a claim for therapeutic equivalence with enoxaparin (Sanofi-Aventis’ Lovenox) based on non-inferiority studies regarding the use of both after total hip or total knee replacement respectively.

The PMCPA pointed out that such studies show the difference between two medicines is not considered clinically important.

The thrust of the GP’s argument was that claiming equivalence was misleading, exaggerated the facts, could not be substantiated and endangered patients’ safety by suggesting Pradaxa was as safe as Lovenox.

While the PMCPA panel did not accept that the ad implied Pradaxa’s superiority it did find that the ad, containing an image of perfectly balanced scales, implied Pradaxa “had been shown to be unequivocally equivalent to enoxaparin and that was not so”.

Since that was misleading, it breached clauses 7.2 and 7.3. The claim could also not be substantiated (7.4) and did not reflect the available evidence about the safety of Pradaxa (7.9).

The ad also contravened clause 7.10, which says that a medicine must be presented “objectively and without exaggerating its properties”, and “all-embracing claims must not be made”.

The panel turned down complaints about doses not being stated on the ad although when the complainant appealed against this the PMCPA did reiterate it was “good practice” to include the relevant dosage particulars.

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Boehringer Ingelheim - Pradaxa: results to RELY on?

Boehringer Ingelheim has presented “groundbreaking results” from a huge late-stage study which show that its oral anticoagulant Pradaxa significantly reduced the risk of stroke compared with warfarin, without raising the risk of bleeding.

The Phase III data presented at the European Society of Cardiology meeting in Barcelona and published in the New England Journal of Medicine involved over 18,000 patients in 44 countries. The study, called RE-LY, demonstrated that patients taking 150mg of Pradaxa (dabigatran etexilate) enjoyed a 34% lower risk of stroke and systemic embolism, compared with those taking warfarin, the blood thinner derived from rat poison sold by Bristol-Myers Squibb as Coumadin but now available generically.

Boehringer also noted that patients on 110mg of Pradaxa experienced similar reductions in stroke and systemic embolism compared to warfarin, but also had a 20% reduced risk of major bleeding. The drug also demonstrated superior reductions in haemorrhagic strokes and vascular mortality.

The response to RE-LY from clinicians was overwhelmingly positive. Stuart Connolly of the McMaster University in Hamilton, Canada, and co-principal investigator of the study, said the results “exceeded all our expectations”. He added that “we now have an oral treatment which offers superior protection from stroke with less bleeding and without the need for routine monitoring”.

Even more enthusiastic was Michael Ezekowitz of the Lankenau Institute in Philadelphia and US lead researcher of RE-LY, who hailed the results as “the first breakthrough in 60 years for preventing stroke in patients with atrial fibrillation.” He added that “the magnitude of these results cannot be understated”, noting that Coumadin, while “highly effective” is “very difficult to control” and Pradaxa is “potentially more effective and safer”.

Dr Ezekowitz pointed out that warfarin takes four days to work, while dabigatran acts within two hours, has very few drug-to-drug interactions and does not require patient monitoring. He added that if the dosage of a blood thinner is too high, the patient can experience bleeding and if it is too low, a stroke can occur, but “this trial not only identified a drug that is more effective than Coumadin, it also revealed the precise dosage that needs to be administered”.

The German drugmaker’s chairman, Andreas Barner, said Pradaxa could “revolutionise anticoagulant treatment” and “we look forward to expeditiously submitting these results to regulatory authorities around the world”. The treatment is available in over 40 countries for the primary prevention of venous thromboembolic events in adults who have undergone elective total hip or total knee replacement surgery; an approval in AF should push it into blockbuster territory.

The RE-LY study puts Pradaxa closer to approval in this indication than rival drugs, notably Bayer/Johnson & Johnson's Xarelto (rivaroxaban) and, further down the line, Pfizer/Bristol-Myers Squibb's apixaban and Merck & Co's betrixaban.

By Kevin Grogan
PharmaTimes

Study Finds Risk In New Stroke Drug Pradaxa - WSJ.com

The original Pradaxa study the company used to gain FDA approval suggested a small increased risk of heart attack with the use of the drug compared to warfarin. Researchers since then have been trying to figure out whether there's really an increased risk. The study found the drug cut the risk of strokes by 35%.

According to an analysis by two Cleveland Clinic researchers published online in the Archives of Internal Medicine, Pradaxa boosted the risk of a heart attack and a condition known as acute coronary syndrome by 33%. The analysis involved more than 30,000 patients and compared those on Pradaxa to others in control groups, who received another blood-thinner like warfarin or enoxaparin, or a placebo.

The study's lead researcher Ken Uchino, a Cleveland Clinic neurologist, said the actual increase in the number of heart attacks and acute coronary syndrome events was very small and is outweighed by the benefit of the drug's ability to reduce the number of strokes. These events occurred in 1.19% of the Pradaxa patients, and in 0.79% of the control-group patients. Dr. Uchino and other researchers called for more study of the drug's potential to increase heart-attack risk.

via online.wsj.com

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Boehringer Ingelheim - Pradaxa: anatomy of a product launch contd.

The story so far.

German privately owned pharmaceutical company Boehringer Ingelheim said the Scottish Medicines Consortium (SMC) has accepted its blood-thinning drug Pradaxa for routine use in the National Health Service (NHS) of Scotland.

The drug prevents venous thromboembolic events in adults who have undergone total hip or knee replacement surgery, the company said.

The European Commission granted marketing authorisation for Pradaxa, which rivals Bayer AG.'s Xarelto and Bristol-Myers Squibb Co.'s apixaban, in all 27 EU member states in March 2008.

The company also said the Danish Institute for Rational Pharmacotherapy (IRF), which belongs to the Danish Medicines Agency, has endorsed Pradaxa as a good alternative to low molecular weight heparins (LMWH) both with respect to efficacy and ease of use.

Boehringer Ingelheim said it is still evaluating the efficacy and safety of Pradaxa to prevent strokes, to treat acute venous thromboembolic events and to prevent heart attacks in patients with acute coronary syndrome.

Pradaxa patient's death draws more scrutiny of bleeding risks - FiercePharma

The case of a Pradaxa user who died after a minor fall is raising more questions about the drug's safety. As the FDA investigates a series of deaths in Pradaxa patients, a new report in the Journal of Neurosurgery details an 83-year-old man's death from a small brain hemorrhage that quickly grew, and didn't respond to efforts to stop it.

"In the event of traumatic hemorrhage in patients receiving dabigatran ... there are currently no effective reversal agents," the report said (as quoted by Reuters). Because Boehringer Ingelheim's Pradaxa is cleared by the kidneys, dialysis has been suggested to neutralize its anticoagulant effects. This particular patient wasn't put on dialysis because "it was too late to implement effectively" as his condition rapidly deteriorated, the article states.

via fiercepharma.com

Posted via email from Jack's posterous

Boehringer Ingelheim - Pradaxa: anatomy of a launch contd.

Back story here.

Chandler Chicco Agency offshoot Litmus, based in London, is in charge of the global PR programme for Pradaxa.

The account is led by Camilla Bull, who is well-versed in this area: she used to work on AstraZeneca's Exanta, an anti-VTE drug that was withdrawn two years ago after it was found to cause liver problems.

Wave Healthcare Communications handles media relations for Pradaxa in the UK and Wave founding director Rod Ball leads the account.

Anthony Y. Lauw is the Senior International Product Manager for Pradaxa at Boehringer Ingelheim.

Tales from the PMCPA contd. The Case of the Unsolicited Email

A medical director of a primary care service provider complained that a promotional email about Pradaxa (dabigatran) had been sent by a third party to his NHS account. Pradaxa was Boehringer Ingelheim’s product for prevention of stroke and systemic embolism in certain patients.

The complainant alleged that the email had been sent unsolicited. The complainant did not request any such information and had not given his email address to any party in connection with either Pradaxa or any other medicine. The complainant could not find a link to unsubscribe from the distribution list. The complainant stated that his complaint was about a breach of both UK law and the Code.

The Authority advised that it could only consider complaints within the context of the Code.

The detailed response from Boehringer Ingelheim is given below.

The Panel noted Boehringer Ingelheim’s submission that the database provider obtained consent from the complainant when he completed his registration. An email to the complainant in February 2011 described the registration process for another service and explained that from time to time information would be sent ‘… by e-mail about our associated/affiliated companies and their clients’ product and services, which may include updates on specialist services, conferences and seminars, diagnostic, medical and pharmaceutical promotional materials as well as official information’. This was followed by a new paragraph ‘However, please be advised that we will not share your e-mails with any third parties’. The unsubscribe facility which stated ‘If you do not wish to receive such information please click the box*’ appeared at the very end of the email after the signature and contact details. Additionally, members of the database had been emailed an opt-in policy which included the following: ‘All our e-mail communications to healthcare personnel, in accordance within the Data Protection Act 2001 include an ‘unsubscribe’ option which allows recipients to ‘opt-out’ if they wish. They can ‘opt-out’ of receiving promotional material only and still receive official information. If a recipient chooses to ‘opt-out’ of receiving promotional material we will stop sending messages to that person’. The policy also referred to contact by email and telephone to update and validate information wherein recipients would be told they had opted-in to receive emails from the service provider and their affiliates which might contain promotional information. The Panel did not have a copy of the covering email providing a copy of the policy to the complainant.

The Panel noted that the database was used to email campaigns on behalf of government departments and agencies which many NHS employees would consider important information and want to receive. The Panel considered that it was not at all clear on the registration email sent to the complainant in February 2011 that he could consent to receive official information by email but choose not to receive promotional material. It was not acceptable to rely on the opt-in policy which was sent separately in this regard. Although it was clear on the registration email that the complainant would receive, inter alia, promotional material for medicines on registration, recipients might choose not to unsubscribe given the impression from the wording of the email and the positioning of the unsubscribe option that they would otherwise not receive any material by email including official information. This was not satisfactory and in the Panel’s view should be improved. The Panel queried whether the recipient was given a bona fide choice. Nonetheless the Panel considered that by registering on the site and failing to unsubscribe, the complainant had given prior permission to receive, inter alia, promotional material by email and no breach of the Code was ruled.

The Panel noted Boehringer Ingelheim’s submission that the unsubscribe facility was omitted in error from the Pradaxa email. The Panel noted that the unsubscribe option did not appear in the version of the email certified by the company. This was a serious error. A breach of the Code was ruled as acknowledged by Boehringer Ingelheim.

http://www.pmcpa.org.uk/files/2437%2013%20Dec.pdf

Clot Wars contd. - Xarelto vs Pradaxa, FIGHT!

Back stories here.

The UK's NICE has approved Bayer's anti-clotting treatment Xarelto, bringing it into line with Boehringer Ingelheim's rival Pradaxa.

Xarelto (rivaroxaban) was assessed under NICE's rapid single technology appraisal work programme and found to be a cost effective option for preventing blood clots.

The drug was launched in the UK last year and Bayer predicts it could reach blockbuster status with sales of more than 2 billion euros ($2.8 billion).

Both Xarelto and Pradaxa are indicated for the prevention of venous thrombembolic events (VTE) in adults who have undergone hip or knee replacements.

More

Clot Wars contd. - Boehringer wins first US OK in blood-thinner race | Reuters

Oct 19 (Reuters) - German drugmaker Boehringer Ingelheim won the first U.S. approval for a new stroke-fighting medicine that will compete in an estimated $10 billion market for drugs to replace the 65-year-old blood thinner warfarin.

The Food and Drug Administration cleared Boehringer's drug, Pradaxa, for preventing strokes in patients with a type of irregular heart beat.

The approval gives Boehringer a head start over several other drugmakers, including partners Bayer (BAYGn.DE) and Johnson & Johnson (JNJ.N), and Bristol-Myers Squibb Co (BMY.N) and Pfizer (PFE.N), that are working on competing drugs.

Pradaxa and potential rivals are alternatives to warfarin, a problematic medicine originally developed as rat poison.

Warfarin is the treatment of choice for people at high risk of stroke due to atrial fibrillation, a common form of irregular heart beat. But the drug interacts badly with food and other medicines, carries a high risk of bleeding and requires regular blood tests.

In September, an FDA advisory panel voted 9-0 to recommend approval of Pradaxa, which also carries a risk of serious bleeding.

The warfarin replacement market is expected to be worth more than $10 billion a year and possibly as much as $20 billion.

via reuters.com

Posted via email from Jack's posterous

Boehringer Ingelheim - Pradaxa: anatomy of a launch

A new oral direct thrombin inhibitor Pradaxa® (dabigatran etexilate) was launched in the UK today.

It is approved for the prevention of venous thromboembolic events (VTE) in adults who have undergone elective total hip or total knee replacement surgery.

More information here.

European approval was based on data from the phase III RE-NOVATE and RE-MODEL studies, which indicated that both 150mg and 220mg of Pradaxa were as effective and safe as injectable enoxaparin (40 mg) in preventing VTE and all cause mortality following total hip replacement surgery and total knee replacement surgery in the RE-NOVATE and RE-MODEL trials, respectively.

Both studies reported a low incidence and severity of major bleeding, similar to enoxaparin. In addition, the rates of ALT elevations > 3x times the upper limit of normal were reported to be low and comparable to enoxaparin.

The PR flaks were hard a work.

It made the BBC Breakfast TV show.

And a charity was there ready to welcome it.

The UK charity Lifeblood's medical director, Dr Beverley Hunt, said: "The prevention of blood clots with blood thinners after surgery is not done well in the UK."

"The need for and potential impact of a generally well-tolerated oral anticoagulant that does not require monitoring is profound."

Here's what they're saying about it on their website.

Hmmmm. Watch this space.

Clot Wars contd. - load up!

The market for new blood thinners including Johnson & Johnson and Bayer AG’s Xarelto could eventually reach $12 billion to $15 billion a year, Bayer Chief Executive Officer Werner Wenning said.

Safety and effectiveness will determine how the anti- clotting pill fares against rivals from Pfizer Inc., Bristol- Myers Squibb Co. and Boehringer Ingelheim GmbH, Wenning said at a dinner with journalists at Bayer’s headquarters in Leverkusen, Germany. Xarelto is already competing “very well” against Boehringer’s Pradaxa in hip and knee surgery patients outside the U.S., he said.

“It’s a very important asset,” Wenning said. Xarelto sales could exceed 2 billion euros ($2.6 billion) a year, he said. Wenning didn’t say when he expects the market for blood- thinners to reach his projected peak.

Family owned German drugmaker Boehringer is ahead in the race for U.S. approval of the first alternative to warfarin, a powerful and dangerous blood thinner derived from rat poison. The Food and Drug Administration is scheduled to issue preliminary findings tomorrow on whether Pradaxa should be approved to prevent strokes caused by blood clots in patients with an irregular heartbeat, a use that makes up the majority of the warfarin-replacement market. An advisory panel meets to discuss the drug on Sept. 20.

Positive Recommendation

The panel is likely to recommend Pradaxa be approved, Emmanuel Papadakis, a London-based analyst for Collins Stewart, wrote in a note to investors on Sept. 13.

Doctors rely on warfarin and aspirin to ward off strokes among 2.2 million Americans with atrial fibrillation, an irregular heartbeat that prevents the organ from properly pumping blood out of its upper chamber. The resulting clots may cause a stroke if they get stuck in the artery to the brain.

Bayer has said it will present results of a study of Xarelto in atrial fibrillation patients at the American Heart Association meeting in November. The German drugmaker said Aug. 31 it will seek U.S. regulatory approval next year for Xarelto for hip and knee surgery patients, after the FDA asked for more information about the drug at its initial review in May 2009.

Bristol-Myers and Pfizer are expected to have results next year for apixaban, a third warfarin-replacement candidate for irregular heartbeat patients. The experimental drug beat aspirin at preventing strokes in a study released last month.

via bloomberg.com

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Bayer, Amgen Face Price Cuts as German Panel Expands Drug Review

Bayer AG (BAYN) and Amgen Inc. (AMGN) are among drugmakers who may face price cuts as a German agency begins a broader review of the costs and benefits of medicines already on the market.

Bayer’s blood thinner Xarelto, Amgen’s Prolia for osteoporosis and painkillers like Nucynta from Gruenenthal Pharma GmbH and Johnson & Johnson (JNJ) are among the targeted products, the Federal Joint Committee decided in a meeting today. The review encompasses other treatments in the same category as each of those medicines, meaning that Boehringer Ingelheim GmbH’s blood thinner Pradaxa will also be assessed.

The analysis is the first step down a path that may end in price cuts. The results of each cost-benefit assessment will form a basis for price negotiations between drugmakers and Germany’s statutory insurers, part of a law passed in November 2010 as Chancellor Angela Merkel’s government sought to save more than 2.2 billion euros ($2.87 billion) in spending on medicines.

Though price talks on newly introduced drugs started in 2011, this is the first time the agency has laid out broad plans to target medicines that were on the market before then, Kai Fortelka, an agency spokesman, said in a telephone interview before the meeting.

Bayer had expected Xarelto to be called up for a cost- benefit analysis, and had prepared, the Leverkusen, Germany- based drugmaker said in an e-mailed statement. Bayer declined to comment in more detail until the analysis is finished.

Boehringer spokesman Reinhard Malin said that the Ingelheim, Germany-based company had expected the review, and that it was confident that Pradaxa’s benefits would be shown.

Spokespeople for Amgen, Gruenenthal and J&J weren’t immediately available for comment.

The Federal Joint Committee is scheduled to hold a press conference about the price review today at 4 p.m. in Berlin.

To contact the reporter on this story: Naomi Kresge in Berlin at nkresge@bloomberg.net

To contact the editor responsible for this story: Phil Serafino at pserafino@bloomberg.net

http://www.bloomberg.com/news/2013-04-18/bayer-amgen-face-price-cuts-as-german-panel-expands-drug-review.html?