Warfarin may have dominanted the $10 billion market for anticoagulants for the past 50 or so years, but a new class of drugs that works in an entirely new way is quickly relegating warfarin's use to the dustbin. Factor Xa inhibitors that keep blood clots from forming without targeting vitamin K like warfarin are generating billions of dollars per year in sales.
Currently, Bristol-Myers Squibb (NYSE:BMY) and Pfizer Inc.'s (NYSE:PFE) Eliquis is the top-selling factor Xa, but other companies are also fighting for share, including Johnson & Johnson (NYSE:JNJ), which markets the blockbuster Xarelto. Can Eliquis keep Bristol-Myers Squibb and Pfizer on top in this indication?
Although warfarin is effective, it's got a host of drawbacks that create problems with adherence and pose safety risks. Warfarin works by blocking the formation of vitamin K–dependent clotting factors. However, it can be tricky to get the dosing right. Patients must be regularly tested to make sure they're taking the right amount of warfarin to prevent clots but avoid bleeding events. Warfarin also imposes dietary restrictions on patients to reduce vitamin K intake. Warfarin use has also resulted in life-threatening brain hemorrhages.
Clearly, warfarin isn't a perfect drug, and perhaps that's why Eliquis, Xarelto, and other factor Xas are having so much success. Unlike warfarin, this new class of drugs inhibits factor Xa, an important cog in blood coagulation. By targeting factor Xa, instead of vitamin K, these drugs can be as effective as warfarin, without warfarin's drawbacks.
The battle being won
Johnson & Johnson's Xarelto was the first factor Xa drug to hit the market, winning Food and Drug Administration approval in 2011. Eliquis came shortly thereafter in 2012.
Both drugs are approved for similar patient populations. For example, doctors can prescribe either Xarelto or Eliquis to help prevent deep vein thrombosis in patients following knee or hip replacement. Similarly, either drug can be prescribed to help prevent blood clots in patients with non-valvular atrial fibrillation, an irregular heartbeat that can lead to life-threatening blood clots.
In trials, Xarelto and Eliquis demonstrated efficacy that was in line with warfarin. However, Eliquis outperformed warfarin in safety. In trials, Eliquis patients had fewer bleeding events than warfarin patients.
Eliquis outpeforming warfarin may be a big reason why its sales are growing much more rapidly than Xarelto's. In 2016, Xarelto sales jumped 22.5% to $2.3 billion. Meanwhile, sales of Eliquis skyrocketed 80% to $3.3 billion. Eliquis' momentum in the fourth quarter suggests that the gap between the two drugs may widen. In the fourth quarter, Xarelto's sales climbed 21% to $598 million, while Eliquis' sales soared 57% to $948 million. At those rates, Xarelto exited 2016 at a $2.4 billion sales clip, while Eliquis' sales exited 2016 at a $3.8 billion pace.
More room to run?
Warfarin still maintains market share north of 30% and one reason is that there isn't an antidote for factor Xa drugs on the market yet. Until an antidote is approved, these factor Xa medications are unlikely to get used in sick elderly patients, who are most at risk of a bleeding event such as a fall.
Fortunately, an antidote could be on the horizon. With financial help from factor Xa drugmakers, Portola Pharmaceuticals developed AndexXa, a treatment that can reverse the anticoagulation effect of Xarelto and Eliquis. It's not clear when the FDA might weigh in with a decision on AndexXa, but if it gives the antidote a green light, then factor Xa sales should climb.
Given that warfarin continues to hold onto a big share of this market, billions of dollars in sales are still up for grabs for factor Xa drugmakers, and if 2016's results are any indication, it seems Bristol-Myers Squibb and Pfizer are best positioned to benefit.