Brilinta Boost For AZ In Stroke Study
Outperforms Aspirin Alone In 11,000-Patient Trial
Sales of AstraZeneca PLC's Brilinta are set to expand after the anticoagulant finally demonstrated benefit over aspirin in preventing stroke in a large late-stage trial.
The UK firm has announced topline results from the Phase III THALES study which showed that Brilinta (ticagrelor) 90mg, used twice daily and taken with aspirin for 30 days, reached a significant and clinically meaningful reduction in the risk of the primary endpoint of stroke and death, compared with aspirin alone. The trial included more than 11,000 patients with minor acute ischemic stroke or high-risk transient ischemic attack (TIA) randomized to treatment within 24 hours of symptom onset
The full THALES results will be presented at a forthcoming medical meeting but they represent something of a turnaround in fortune for Brilinta in stroke.
Some four years ago, the SOCRATES trial evaluated treatment with Brilinta alone compared with aspirin in the same type of patients as THALES but over a longer period (90 days). The primary efficacy endpoint of time to first occurrence of an event such as stroke, heart attack or death was not met in SOCRATES. (Also see "Brilinta No Better Than Aspirin In Stroke Trial" - Scrip, 24 Mar, 2016.)
AstraZeneca had better luck with the THEMIS trial. That study, presented at the European Society of Cardiology annual congress in Paris in September 2019, showed that the Brilinta/aspirin combination reduced the relative risk of a composite endpoint event (cardiovascular death, heart attack, or stroke) by 10% compared with aspirin alone; a subgroup of patients with previous percutaneous coronary intervention (PCI) saw a better than average response, with a 15% reduction on the endpoint. (Also see "AstraZeneca Aiming To Extend Brilinta Use In PCI patients" - Scrip, 2 Sep, 2019.)
The THALES results went down well with analysts and SVB Leerink issued a note on 27 January stating that the preliminary safety data were consistent with the known safety profile for the drug. While there was an increased bleeding rate in the treatment arm, "we view Brilinta success in stroke as an important addition to the label."
Over at Jefferies, analyst Peter Welford issued a note saying that there are about 2.2 million ischemic stroke patients in major markets, "a substantial expansion over the current acute coronary syndrome indication" for the P2Y12 receptor agonist of about 4.3 million patients. He forecast $2.5bn in worldwide peak sales, assuming patent expiry by 2024.
Bryan Garnier analyst Eric Le Berrigaud noted that the THALES success was far from being taken for granted given the SOCRATES failure, but testing a slightly different hypothesis using the Brilinta/aspirin combo for a shorter duration of time has paid off. He added that detailed results of the increased incidence of bleeding events "will have to be factored in to get a full assessment of the market opportunity."
Brilinta, which is also indicated for patients with a history of myocardial infarction and a high risk of developing an atherothrombotic event, is a big earner for AstraZeneca and third quarter revenues rose 27% to $416m. However, the drug has not reached the commercial potential set out by CEO Pascal Soriot when he was fighting off the attentions of Pfizer back in 2014. (Also see "AstraZeneca Makes Case For Independence With $23 Bil. Pipeline Potential" - Pink Sheet, 6 May, 2014.) (Also see "Game over as AstraZeneca rejects final $119bn Pfizer bid" - Scrip, 19 May, 2014.)
Nearly six years ago, Soriot said AstraZeneca forecast that Brilinta would have sales of $3.5bn in 2023 but the firm admitted in 2016 that the target was unattainable. The lowering of guidance came after the SOCRATES blow and results from the EUCLID trial where Brilinta did not show a benefit compared with the older, generic blood thinner clopidogrel in treating peripheral artery disease. (Also see "AstraZeneca Says $3.5bn Brilinta Sales Forecast By 2023 Now Unattainable" - Scrip, 4 Oct, 2016.)
Nevertheless, Brilinta is still a key driver for AstraZeneca's CVRM (cardiovascular/renal medicine) franchise. One of the other products for which the firm has high hopes in that area is the diabetes pill Farxiga (dapagliflozin) for the treatment of heart failure and the US Food and Drug Administration recently granted a priority review for the therapy for the reduction of cardiovascular death or worsening of heart failure in adults with reduced ejection fraction both with and without type 2 diabetes. (Also see "AZ’s Farxiga Gets FDA Priority Review For Heart Failure" - Scrip, 6 Jan, 2020.)
In an interview with Scrip at the J.P. Morgan Healthcare conference in San Francisco last month, AstraZeneca biopharmaceuticals president Ruud Dobber noted that "there is a lot of attention [on] the breakthroughs in oncology but we need to understand the number one killer in the world is still cardiovascular disease by far."
AstraZeneca noted that stroke is the second leading cause of death worldwide, with 6.2 million stroke-related deaths in 2017.