Trial investigators released the results from a 351-day, 3,396-patient study, known as Einstein Choice, showing that patients with venous thromboembolism (VTE) taking Xarelto (rivaroxaban) — either 10 mg or 20 mg once daily over an extended time period — had significantly fewer recurrent blood clots and similar rates of major bleeding compared to those taking 100 mg of aspirin once daily. Specifically, 10 mg of Xarelto reduced the risk of recurrent VTE by 74 percent, and 20 mg by 66 percent. The study comprised patients who previously suffered a VTE, and was designed to test Xarelto’s ability to prevent a recurrence. The findings were presented last week during a Joint American College of Cardiology/Journal of the American Medical Association Late-Breaking Clinical Trials session at the American College of Cardiology’s 66th Annual Scientific Session, and published contemporaneously in The New England Journal of Medicine.
VTE, which includes deep vein thrombosis (DVT) and pulmonary embolism (PE), affects more than 900,000 Americans each year, with one-third of these occurrences being fatal. According to the American Heart Association, VTE is the third most common vascular diagnosis behind heart attacks and strokes. According to Philip S. Wells, MD, Professor, Chair and Chief, Department of Medicine, University of Ottawa, and Senior Scientist, The Ottawa Hospital, Ontario, Canada, who presented the work, the study was the first to test Xarelto’s ability to prevent VTEs in a head-to-head contest against aspirin. “How best to extend anticoagulant use beyond the initial treatment window has been a constant source of debate, with physicians carefully balancing patients’ risk of another VTE with the risk of anticoagulant-related bleeding. With Einstein Choice, for the first time we have clinical evidence confirming rivaroxaban is superior to aspirin in reducing recurrent VTE, with no significant impact on safety. These important results have the potential to trigger a paradigm shift in how physicians manage their patients and protect them from VTE recurrence over the long term.”
Notwithstanding the favorable results for Xarelto, its list price of $12.93 per tablet regardless of dose (with accounting for negotiated rebates and discounts), makes it significantly more expensive than aspirin. Moreover, as stated in this firm’s January 27, 2017 blog post (Big Pharma: Xarelto, Eliquis and the Anticoagulant Market), Johnson & Johnson’s Xarelto is one of the three major direct oral anticoagulants (DOACs) poised to replace warfarin, together with Pfizer’s Eliquis and Boehringer Ingelheim’s Pradaxa, and Daiichi’s Savaysa. According to 2016 VTE treatment guidelines from the American College of Cardiology, Xarelto, Pradaxa, Eliquis and Savaysa are recommended in the condition over warfarin. As all patients with VTE are at risk of having another occurrence, guidelines currently recommend anticoagulant therapy with a DOAC for at least three months.
According to data from a study of United States Medicare patient records comparing DOACs with warfarin, Pradaxa patients displayed a similar risk of stroke but a significantly lower risk of major bleeding, Xarelto patients were at a significantly lower risk of stroke but significantly higher risk of major bleeding, and Eliquis patients had a significantly lower risk of both. From a financial perspective, the per patient costs from a major bleeding-related event were as follows: Xarelto – $542, warfarin – $500, Pradaxa – $367, and Eliquis – $286. However, a high percentage of patients still take old standby warfarin given that if bleeding begins while a patient is on warfarin, the effects are easily reversible with Vitamin K and fresh frozen plasma, whereas if bleeding begins when patients are on Xarelto or Eliquis, no reversal agents exist. Pradaxa maintains Praxbind, released in 2016, as its reversal agent.
Despite Xarelto’s apparent success, the drug is still plagued by lawsuits and negative press:
- Pursuant to the Physician Payments Sunshine Act — a 2010 bipartisan bill passed as part of the Affordable Care Act — the public can see which “Big Pharma” manufacturers pay doctors under the guise of promotional speaking fees, consulting fees, travel costs, meals, gifts, and royalties in order to maintain and grow market share for their products. The non-profit organization, ProPublica, conducted studies confirming that doctors who receive payments from drug companies are more than likely to prescribe those brand-name drugs than doctors who do not receive payments. ProPublica’s latest report revealed that, in 2014 and 2015, approximately $2 billion was given to more than 600,000 doctors and another $600 million for each year was given to teaching hospitals. The “Top Ten” list, known as the “Dollars for Docs” Database, has Xarelto at the top of the recipient list with $28.4 million paid to health care providers in order to encourage them to prescribe Xarelto in 2015. That same year, Xarelto sales exceeded $4.3 billion – representing a 1500% return on investment.
- Further, there are presently over 15,000 lawsuits consolidated in multidistrict litigation before Judge Eldon E. Fallon in in the Eastern District of Louisiana (In re: Xarelto Products Liability Litigation, MDL No. 2592). The Xarelto lawsuits allege that the drug’s manufacturers — Bayer Healthcare and Johnson & Johnson subsidiary Janssen Pharmaceuticals — failed to warn about Xarelto’s potential risks, most notably, uncontrollable bleeding. Further, plaintiffs have alleged that they were unaware that Xarelto was brought to market without an effective antidote, or reversing agent, which can help stem a Xarelto bleeding issue that could lead to death, whereas the blood thinning properties of warfarin can be reversed through the use of Vitamin K. Further, plaintiffs maintain it was irresponsible of the manufacturers to claim less monitoring of patients on Xarelto was needed when, in the absence of an antidote, more monitoring would be required.