Eliquis stacks up better than Pradaxa or Xarelto
It looks as though Eliquis, the new bloodthinner being developed by Bristol-Myers Squibb and Pfizer, has lived up to all the hype. Data from a closely watched clinical trial, presented at a cardiology meeting in Paris last weekend, demonstrated in convincing fashion that the drug is superior in efficacy and bleeding profile to standard warfarin therapy.
Among patients with atrial fibrillation, Eliquis (apixaban) bested warfarin in preventing strokes while also reducing the risk of bleeding by a statistically significant 31%. What's more, Eliquis cut the risk of death from any cause by 11%, making it the first of a new crop of anticoagulants to significantly move the needle on mortality.
Those data points, from a trial called Aristotle, are likely to form a solid case for FDA approval to prevent strokes in atrial fibrillation (a condition called SPAF), and a very compelling sales narrative for the drug in the market against the other warfarin substitutes, Boehringer Ingelheim's Pradaxa (dabigatran) and Johnson & Johnson/Bayer's Xarelto (rivaroxaban), whose approval for SPAF is pending.
Eliquis' efficacy in preventing strokes proved about as good as Pradaxa's and slightly better than Xarelto's. Pradaxa, which like Eliquis is dosed twice daily, demonstrated superior efficacy but not safety vs. warfarin, and Xarelto was non-inferior to warfarin on efficacy and safety, with once-daily dosing.
While a New England Journal of Medicine editorial accompanying the journal's publication of the study noted that all three drugs have about a 10% mortality risk reduction from any cause compared to warfarin, expect Pfizer/BMS reps to hammer home the point that their Eliquis is the only one to show it with statistical significance (see table below).
| Comparing the new anticoagulants
|Risk of stroke or embolism (efficacy)
|Risk of death (all-cause mortality)
|Risk of major bleeds (safety)
|* Not statistically significant
|Sources: RE-LY (Pradaxa), ROCKET-AF (Xarelto) and Aristotle (Eliquis) trial data; Mark Schoenebaum/ISI Group|
But it's Eliquis' steep reduction in bleeding risk, as shown in the trial, that will drive commercial uptake, said ISI Group analyst Mark Schoenebaum. "Don't focus on efficacy; bleeding profile is what sets the drug apart," he said. "Medically speaking, it's hard to see why physicians wouldn't reach for this drug as a first choice."
One reason they might choose something else is cost. Warfarin and aspirin, because of their low cost, will retain 20% of the non-valvular AF market, Schoenebaum predicts. The other 80% amounts to a $6.5 billion opportunity ($3.5 billion US), of which Eliquis will grab some 60%, or $4 billion, by 2020 (the year Pradaxa goes off patent), he said.
Seamus Fernandez of Leerink Swann put peak Eliquis sales at $4.2 billion in 2017. In his estimation, Pfizer's and Bristol's marketing pedigree, which includes Lipitor and Plavix (the two biggest cardiovascular blockbusters) should help them deliver on Eliquis' potential to replace warfarin in AF, or to help those who cannot tolerate the older drug. Other indications could be worth $3 billion to $6 billion worldwide.
Bernstein analyst Tim Anderson said the side-by-side data should help Eliquis compensate for its likely third-to-market timing in SPAF, behind Pradaxa and Xarelto, whose approval in the AF setting will be discussed Sept. 8th at an FDA advisory committee meeting (Anderson expects approval). Anderson modeled Eliquis sales of $2 billion in 2015, an increase from his earlier $1.4 billion forecast issued after BMS and Pfizer previewed Aristotle results in June. He is maintaining his $1.9 billion worldwide sales forecast in 2015 for Xarelto.
A dark horse at this point is edoxaban, another factor Xa inhibitor in development by Daiichi-Sankyo. A phase III study of edoxaban, called Engage, is due to read out in mid-2012. And Portola Pharmaceuticals' betrixaban is in phase II. Time will tell whether either of these drugs challenges Eliquis' leadership in SPAF.