A recent clinical study intended to demonstrate the superiority of Xarelto (rivaroxaban) to aspirin in the prevention of secondary stroke has been abandoned by its sponsors, Bayer and Johnson & Johnson.
The study, known as NAVIGATOR-ESUS, involved 7,000 participants, but failed to give the drug makers the validation they were seeking for their product. Started in 2014 and scheduled to end this coming January, the study was canceled after the data monitoring committee came to the conclusion that there was no appreciable difference in effectiveness when it came to protecting patients at risk for secondary stroke following an “embolic stroke of undetermined origin” (ESUS).
In fact, the rate of bleeding was actually higher for subjects receiving Xarelto than those who were treated with low-dose aspirin, which is often prescribed for this purpose. The committee concluded there was “very little chance of showing overall benefit” of Xarelto over aspirin were the trial to continue to the end.
This is not good news for either Bayer or J&J. For several years, Xarelto was the leading new generation anticoagulant among a field of competitors that included Eliquis (apixaban) and Pradaxa (dabigatran). This year, however, Eliquis sales have overtaken those of Xarelto since an analysis of Medicare claims demonstrated a clear superiority over the latter in terms of efficacy and cost-effectiveness. It should be noted that said analysis was sponsored by Eliquis manufacturers Bristol-Meyers Squibb and Pfizer.
An earlier study, EINSTEIN CHOICE, did show that Xarelto was better than aspirin in the prevention of recurrent thrombotic embolism (blood clotting). Bayer and J&J are also optimistic about the results from a current study, COMPASS, which they hope will demonstrate that use of Xarelto as an adjunct treatment to aspirin therapy is more effective in preventing heart attacks and strokes than taking aspirin alone. Again, it bears mentioning that the former study was paid for by Bayer, while the latter is funded by J&J subsidiary Janssen Pharmaceuticals. Bayer and J&J have announced their intention to seek FDA approval for this indication before the end of 2017. According to analysts, such approval could boost Xarelto sales by $1.5 billion.
In the meantime, Bayer and J&J continue to face lawsuits over Xarelto. Plaintiffs allege that the medication was responsible for their bleeding injuries and that the manufacturers were aware of the lack of an antidote, failing in their duty to warn physicians and patients of the dangers.
So far, the defendants have prevailed in the first three bellwether trials. However, Xarelto litigation is just getting underway; 37 more bellwether trials are scheduled in the coming months, and over 18,600 lawsuits have been filed. In addition, there have been doubts about the accuracy and objectivity of the initial study comparing Xarelto’s efficacy to that of warfarin, the standard treatment for patients at risk of embolism since the early 1950s.
Currently, there is no approved antidote for new generation, or “novel oral anticoagulants” (NOACs) such as Xarelto and Eliquis. A reversal agent has been in development at a small San Francisco biotech firm for some time, but it has yet to get a green light from the FDA. The federal regulatory agency is expected to make a decision in February.