Eliquis Pushed Amid Bleeding Problems with Xarelto, Pradaxa

Amid mounting concerns about the risk of fatal bleeding on Xarelto and Pradaxa, the makers of Eliquis are pushing forward with aggressive marketing for the third drug in this new class of anticoagulants, which also lacks an approved reversal agent that could allow doctors to stop hemorrhaging or bleeding that may develop among users.

Eliquis (apixaban) is jointly manufactured by Pfizer and Bristol-Myers Squibb (BMS), and approved for prevention of strokes among patients with atrial fibrillation. It was introduced in 2012, as the third member of a new generation of blood thinners, known as direct thrombin inhibitors.

Phizer and BMS have recently kicked off a major increase in direct-to-consumer advertising for the drug, and the FDA has just expanded approval for Eliquis to add indications for the prevention and treatment of blood clot-related problems, such as deep vein thrombosis and pulmonary embolism.

Direct thrombin inhibitors have been aggressively marketed by several drug makers in recent years, promoted as superior alternatives to warfarin, which has been the industry standard for anticoagulation therapy for decades. However, use of warfarin requires close blood monitoring during treatment, which the makers of Eliquis, Xarelto and Pradaxa all indicate is not necessary with this new class of drugs.

Pradaxa (dabigatran) was the first member of this new class of blood thinners, introduced by Boehringer Inegelheim in 2010 for the prevention of strokes associated with atrial fibrillation. Shortly after Pradaxa was introduced, it quickly became a “blockbuster drug”, generating over $1 billion per year in sales. However, it also quickly earned the dubious distinction as one of the prescription medications most commonly associated with adverse event reports submitted to the FDA.

Unlike warfarin, direct thrombin inhibitors lack an approved antidote, or reversal agent, which may allow doctors to reverse the blood thinning effects of the medication. When warfarin users begin to suffer a bleeding event, doctors can give them a dose of vitamin K and fresh frozen plasma to quickly stop the anticoagulant effects of the drug. However, no such antidote has been approved for Eliquis, Pradaxa or Xarelto, and all have similar bleeding risks to warfarin.

Amid thousands of reports involving users who suffered uncontrollable bleeding problems, Boehringer Ingelheim faced Pradaxa lawsuits alleging that inadequate warnings were provided about the lack of an approved reversal agent. Earlier this year, the drug maker agreed to pay  $650 million to settle about 4,000 Pradaxa lawsuits, averaging about $150,000 per case.

Xarelto (rivaroxaban) was the second member of this new class of anticoagulants, introduced about a year after Pradaxa. It quickly became the most widely used of the medications, exceeding sales of Pradaxa last year, as the competitor faced negative media attention and mounting lawsuits.

As the popularity of Xarelto has increased, a growing number of bleeding complications have also been associated with this drug.

This year, a growing number of Xarelto lawsuits are now being pursued against the manufacturers, Bayer and Johnson & Johnson. Plaintiffs raise indicate that the benefits provided by the medication do not justify the risks of uncontrollable bleeding, indicating that the drug makers should issue a Xarelto recall until a reversal agent can be developed.

As concerns surrounding Xarelto are mounting, the makers of Eliquis, the third drug in this class, now appear poised to capitalize, pushing for expanded use of their drug and directly marketing the medication to consumers, despite the fact that Eliquis also lacks an approved reversal agent.

Direct-to-Consumer Marketing

Bristol-Myers Squibb has not disclosed their Eliquis advertising budget, but in a recent conference call to investors, company officials said that they had increased advertising and marketing funding by 9%, with Eliquis being a major focus of new direct-to-consumer advertising.

At the end of 2014, the company had a advertising budget of $254 million for the fourth quarter of that year alone. The transcript of the call was published by Seeking Alpha. 

The direct-to-consumer ads are meant to push Eliquis to what investors once expected could be a $3 billion per year market, but which has fallen very short of even the $1 billion blockbuster mark so far. However, Eliquis’ 2014 second quarter revenue was $171 million, a vast increase over the $12 million it made at the same time last year.

The power of direct-to-consumer ads were highlighted in a recent study in Medical Care, which found that they had a disproportionate effect on doctors’ drug choices and often lead to unnecessary prescriptions.

Boehringer Ingelheim recently announced that the FDA has granted “breakthrough status” to fast-track the approval process for a possible antidote to the blood thinner Pradaxa, and Bayer and Johnson & Johnson indicated last year that they are working with a company called Portola Pharmaceuticals to develop an Xarelto reversal agent.

Of all of the new blood thinners, doctors know the least about stopping Eliquis bleeding events. A recent study published in the Journal of Neurosurgery warned that there is an extreme lack of experimental and clinical data available for doctors who need to stop Eliquis bleeds to save patient lives.

“To date, there are no human studies of reversal agents in patients who require rapid (Eliquis) reversal,” the researchers warned.