Oral anticoagulant Eliquis (apixaban) has demonstrated superior efficacy and bleeding profile to standard warfarin therapy. Barring any bombshells, that should be enough for this agent, being developed by Pfizer and Bristol-Myers Squibb, to get US approval and form a compelling sales narrative in the warfarin-alternative market, analysts say.
Despite an FDA panel voting in early September to okay Johnson & Johnson/Bayer's Xarelto (rivaroxaban) for approval to prevent strokes in atrial fibrillation (SPAF), KOLs now view Eliquis as their oral anticoagulant of choice for that indication, according to a Leerink Swann research note.
What most impressed KOLs was data from the Aristotle trial, released in August, showing that Eliquis had an 11% relative risk reduction in mortality and a 31% relative risk reduction in major bleeding. Neither Xarelto nor Boehringer Ingelheim's Pradaxa (dabigatran) can match it in overall mortality or safety.
While a New England Journal of Medicine editorial that accompanied the journal's publication of the Aristotle 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 of the three to actually demonstrate it with statistical significance (see table).
Moreover, if Eliquis secures an FDA nod for SPAF with a mortality benefit, managed care contacts told Leerink that they will not be able to require warfarin to be used first in SPAF, and Eliquis will become the preferred agent, leaving the other two to battle for formulary status.
Meanwhile, once-daily Xarelto's favorable panel vote in September was a cautious “yes,” Leerink notes, suggestive of perhaps a conditional approval, such as a narrower label (in high-risk patients) or as second- or third-line therapy.
Eliquis' steep reduction in bleeding risk will drive commercial uptake, said ISI Group analyst Mark Schoenebaum. “Medically speaking, it's hard to see why physicians wouldn't reach for this drug as a first choice,” he said.
Warfarin and aspirin, because of their low cost, will retain 20% of the non-valvular AF market, Schoenebaum predicted. The other 80% is a $6.5 billion opportunity ($3.5 billion US), of which Eliquis will grab some 60%, or $4 billion, by 2020 (when Pradaxa goes off patent).
Assuming SPAF filing this year and launch early next, Leerink Swann's Seamus Fernandez 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 the potential of Eliquis.
Bernstein analyst Tim Anderson modeled Eliquis sales of $2 billion in 2015, and $1.9 billion worldwide in 2015 for Xarelto.
Other factor Xa inhibitors in development include Daiichi Sankyo's edoxaban, in phase III, and Portola's betrixaban, in phase II.