- Bayer AG and Johnson & Johnson have halted a late-stage clinical study of Xarelto after a third-party review found the stroke drug was unlikely to outperform standard of care.
- While a more complete rundown of the NAVIGATE ESUS trial should come next year, results thus far have shown similar efficacy between Xarelto and aspirin for secondary prevention of stroke and systemic embolism in patients with a recent embolic stroke of undetermined source (ESUS), according to an analysis from an independent data monitoring committee.
- As for safety, the companies said bleeding rates were "very low overall and within the expected range" across the study, yet the experimental arm did demonstrate increased bleeding compared to the aspirin arm. That outcome might have carried less weight under different circumstances, but Bayer and Johnson & Johnson are currently facing a mountain of lawsuits related to Xarelto's internal bleeding risks.
Xarelto (rivaroxaban) used to make up more than half of the novel oral anticoagulant (NOAC) market, but rival therapies have been able to wrestle away some of that share. Eliquis (apixaban), for instance, raked in $1.18 billion for Bristol-Myers Squibb Co. during the second quarter, representing 51% revenue growth year over year. And Boehringer Ingelheim GmBH saw sales of its blood thinner Pradaxa (dabigatran etexilate) rise 8% in 2016 to €1.39 billion (about $1.48 billion).
Bayer and Johnson & Johnson's drug fetched $642 million in the U.S. during the second quarter and $1.16 billion for the first six months of 2016.
Looking to fortify Xarelto against competitors, the companies have worked to rack up indications. The Food and Drug Administration first green lit the medication in 2011 as a prophylaxis for deep vein thrombosis (DVT) in patients undergoing knee or hip replacement surgery. Since then, the agency has approved the drug several more times, including as a general treatment for adults with DVT or pulmonary embolism.
"Xarelto is a highly effective anticoagulant for patients at risk for stroke from atrial fibrillation, as well as for the prevention and treatment of clots in a variety of approved indications," Paul Burton, vice president of medical affairs at Johnson & Johnson's research entity, Janssen Pharmaceuticals Inc., said in an Oct. 5 statement.
It's unclear whether the termination of NAVIGATE ESUS means Bayer and Johnson & Johnson will also stop investigating Xarelto in the corresponding indication. Surely weighing on that decision are two clinical studies assessing Pradaxa and Eliquis in patients with ESUS. Primary completion dates for the studies are set for June and December 2018, respectively.
The large population of ESUS patients may also keep the drugmakers' interested in additional research. Estimates hold that the condition affects roughly half a million people in the U.S. each year, according to Johnson & Johnson.
On the flip side, large cardiovascular trials are often extremely expensive. NAVIGATE ESUS, as an example, enrolled upwards of 7,000 patients and took place at nearly 460 trial sites. Considering the study was curtailed early, the companies may be hesitant to sink more money into another potential failure.
But even if the companies decide not to further pursue ESUS, they are still investigating Xarelto in a medley of diseases, and believe its previous clinical performances — such as the 14,000-patient ROCKET AF study that pitted the drug against dose-adjusted warfarin as a treatment for nonvalvular atrial fibrillation — give it strong legs to stand on.
"Results from ROCKET AF and emerging real-world data continue to show the positive benefit of Xarelto in preventing cardiovascular events, including stroke," Burton said.