With $529 million in Q3 2016 sales, Xarelto (rivaroxaban) is one of Johnson & Johnson’s top pharmaceutical products.
In Q3 2016, Xarelto’s total prescription market share was 17.5%, up 1.7% year over year. Xarelto’s market share growth resulted from the decrease in sales of warfarin, which remains the most prescribed anticoagulant on the market, with a market share of about 55%, down from 62% in Q3 2015. Given Xarelto’s apparent effectiveness, need for less testing, and fewer dietary restrictions than warfarin, Xarelto has experienced double-digit sales growth in every year since launching in 2011, and Q3 2016 sales were up from 14.8% for the same period in 2015.
However, in the United States, Eliquis has become the most preferred oral anticoagulant in the institutional setting, and has also been increasingly prescribed by primary care physicians. Eliquis’ share in the new-to-brand novel oral anticoagulant market is approximately 51.3%, while Xarelto lags behind at 41.7%.
Xarelto is one of the three major direct oral anticoagulants (DOACs) poised to replace warfarin, together with Eliquis and Pradaxa. The Food and Drug Administration (FDA) approved Xarelto for use in patients who had knee or total hip replacement surgery to reduce the risk of blood clots, and also to reduce the risk of stroke in people with atrial fibrillation. Following a fast-track regulatory review, the FDA approved the drug for general treatment of deep vein thrombosis (DVT) and pulmonary embolism (PE). When first released, the manufacturers advertised Xarelto as being the “first and only once-a-day prescription blood thinner”.
A recent study wherein researchers examined the effects of Xarelto, Eliquis, and Pradaxa concluded that all were associated with increased gastrointestinal bleeding, with Xarelto associated with more incidents than the other two. The Mayo Clinic study, published in the medical journal, Gastroenterology, examined data from approximately 57,000 patients with non-valve atrial fibrillation who were prescribed Xarelto, Eliquis or Pradaxa from October 1, 2010 to February 28, 2015 and experienced gastrointestinal bleeding. Incidents of bleeding rose in all groups of patients 75 years-old and older who took any of the three drugs.
Manufacturers of the Xarelto, Eliquis, and Pradaxa claim that the drugs are superior to warfarin in ease of use and reduction in the amount of blood monitoring needed to ascertain that the correct dose of the drug has been prescribed. However, 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. These irreversible bleeding problems can be fatal.
Prior to the 2016 availability of Praxbind — a reversal agent for Pradaxa — Pradaxa faced a number of lawsuits. Following several years of centralized proceedings in a federal multidistrict litigation (MDL), Pradaxa’s manufacturer, Boehringer Ingelheim International GmbH, ultimately settled approximately 4,000 lawsuits for $650 million.
There are over 13,000 Xarelto lawsuits consolidated in federal multidistrict litigation before Judge Eldon E. Fallon in Louisiana (Xarelto Products Liability Litigation, MDL No. 2592). The product liability lawsuits claim that Xarelto manufacturers, Bayer Healthcare and Janssen Pharmaceuticals (owned by Johnson & Johnson), marketed and sold Xarelto with no warning to doctors or patients about the fact that a reversal agent was unavailable. Bellwether trials involving Xarelto will commence in March 2017, which will provide an indication of how juries will respond to evidence and claims likely to be common to all of the filed lawsuits.
Portola Pharmaceuticals has developed a reversal agent for Xarelto and Eliquis, which has been submitted to the FDA for approval. Though the FDA designated Portola’s drug — AndexXa (andexanet alfa) — a Breakthrough Therapy, and granted it expedited review, approval was withheld pending additional information on its manufacture and whether it can be used as a reversal agent for two other blood thinners, Savaysa and Lovenox.