Last week saw yet another blow dealt to AstraZeneca’s hopes for their antiplatelet agent Brilinta (ticagrelor). The October 4th company press release revealed that Brilinta had failed to demonstrate a benefit over clopidogrel in peripheral artery disease (PAD) patients. This news follows in the footsteps of the March 2016 announcement that Brilinta had failed to meet its primary end point in the SOCRATES trial assessing the drug in patients with acute ischemic stroke or transient ischemic attack (see my April 2016 blog). This now leaves Brilinta’s success rate in the PARTHENON clinical development program at 2 - 2, with one trial still in play.
The PARTHENON clinical development program comprises five randomized, controlled, cardiovascular outcome studies, investigating Brilinta in a spectrum of patients with atherothrombotic disease. While the results of two of these trials demonstrated a benefit for Brilinta in patients with acute coronary syndrome (PLATO) and in patients with a history of myocardial infarction (PEGASUS-TIMI 54), both SOCRATES and EUCLID have failed. That leaves the THEMIS trial, which is investigating Brilinta in patients in patients with type 2 diabetes (T2D) at high risk of cardiovascular events. This trial is due to complete in January 2018.
With a diagnosed prevalence of approximately 12 million PAD patients across the G7 markets (United States, France, Germany, Italy, Spain, United Kingdom, and Japan), success in the EUCLID trial would have represented a significant win for Brilinta. Indeed, the evidence supporting use of clopidogrel in PAD comes from a subpopulation analysis, and interviewed thought leaders are eager for an antithrombotic agent to prove its worth in a PAD-specific trial.
“In PAD there's no good data from a single large trial to support any antiplatelet therapy. So everything is based on these compilations of these other trials - many trials together. The data for aspirin is very weak. Clopidogrel is based on a substudy of a larger trial. So I think PAD is a really great opportunity because there's just no single trial that shows: “these patients do well with drug X.” If anything, the best results are for clopidogrel from a substudy. So if you beat clopidogrel, I think that you’d be pretty good for market share.”
- Cardiologist, United States
Annual Brilinta sales in 2015 were $619 million. AstraZeneca has now stated that their annual sales goal of $3.5 billion by 2023 is unattainable. We at DRG still forecast significant sales growth for Brilinta, but see this latest news as a significant setback. Indeed, approximately one-third of branded clopidogrel’s annual sales were estimated to come from its use in PAD and stroke patients. Nevertheless, that still leaves two-thirds of clopidogrel’s annual sales for Brilinta to exploit (annual sales of branded clopidogrel peaked at just over $7 billion in 2011).
We look forward to hearing the full results from EUCLID, expected at the American Heart Association annual meeting in New Orleans in November. We expect that prescribers will be reassured by the safety data from EUCLID, which was reported as being consistent with the known safety profile, and that use in acute coronary syndrome and post-myocardial infarction patients will continue to rise. We also keenly await the results of the THEMIS trial in 2018.