Matthew Killeen, Ph.D.
The anticoagulant market will undergo a sustained period of significant growth over the next 10 years as a series of new oral agents, with vastly superior clinical profiles to warfarin, launch for lucrative indications, such as stroke prevention in atrial fibrillation (SPAF) and venous thromboembolism treatment. The race for dominance in the SPAF market is already underway; dabigatran became the first of a wave of new agents to launch for this indication in October 2010 and rivaroxaban is poised for launch later this year. Although the positive results from Phase III trials of dabigatran and rivaroxaban for SPAF have already established high barriers to entry to this indication, apixaban’s astounding performance in its pivotal ARISTOTLE trial have secured its ability to effectively compete in this arena.
ARISTOTLE, a double-blind Phase III trial of apixaban versus warfarin showed, unequivocally, that apixaban has several major advantages over warfarin that set it apart from rivals. The trial’s primary efficacy end point, ischemic or hemorrhagic stroke or systemic embolism, occurred in 212 patients given apixaban compared to 265 assigned to warfarin (P=0.01). Additionally, the rate of death from any cause was significantly lower in the apixaban arm of the study (603 vs. 669 warfarin-treated patients; P=0.047). While both dabigatran’s and rivaroxaban’s mortality data trended towards statistical significance, thus far only apixaban can claim a clear mortality benefit over warfarin. With regards to safety, apixaban’s data were equally impressive; rates of major bleeding were significantly lower with apixaban, relative to warfarin (major bleeding was documented in 327 vs. 462 patients, respectively; P<0.001)
How do the data from the ARISTOTLE study align with the clinical expectations for new oral anticoagulants for SPAF? A 2011 study by Decision Resources surveyed U.S. cardiologists to develop physician-built target product profiles based on a major drug development opportunity: an anticoagulant with a lower rate of major bleeding than warfarin (1). Our results showed that, at a price point similar to that of dabigatran, physicians would expect major improvements over warfarin’s efficacy in addition to less major bleeding. Based on the results from ARISTOTLE, apixaban is the only oral anticoagulant to satisfy the vast majority of these clinical expectations.
Given apixaban’s powerful Phase III data, how will the SPAF landscape evolve and how will the fortunes of dabigatran and rivaroxaban be impacted? In a forthcoming study, Decision Resources surveyed over 120 U.S. cardiologists and pharmacy directors to gauge perceptions towards Phase III data of the new oral anticoagulants and to determine potential prescribing trends and formulary placement for these agents (2). Our study showed that, by 2012, apixaban’s superior stroke prevention efficacy and significantly lower rates of major bleeding compared to warfarin would fuel its uptake and profoundly impact the use of dabigatran and rivaroxaban. Additionally, our payer research indicated that this clinical profile would result in the most favorable tier placement on formularies of all of the new oral anticoagulants.
With the combined results from the ARISTOTLE and AVERROES trials, apixaban represents an important step-change in therapeutic options for AF patients. We believe that these powerful data will enable apixaban to surpass dabigatran and rivaroxaban to emerge as the sales-leading new oral anticoagulant for SPAF following its launch in 2012.
(1) Atrial Fibrillation: Opportunity Exists for New Antiarrhythmics That Reduce Mortality and Can Be Used in Patients With Heart Failure. DecisionBase, Decision Resources, 2011.
(2) Pradaxa, Xarelto, and Apixban for Atrial Fibrillation: How Have Phase III Data Informed Physicians and Payer Perceptions of These New Anticoagulants? A Survey of Non-Interventional Cardiologists and Managed Care Organization Pharmacy Directors. Physician & Payer Forum, Decision Resources, September 2011.