AstraZeneca acknowledged today that its marketed heart disease treatment Brilinta/Brilique (ticagrelor) missed its primary endpoint in a Phase III trial intended to generate data supporting a potential new indication as a stroke treatment.
Brilinta/Brilique failed to meet the trial’s primary efficacy endpoint of time to first occurrence of any event from the composite of stroke (ischemic or hemorrhagic), myocardial infarction, and death, the company said.
While fewer events were seen in patients taking Brilinta/Brilique compared with aspirin, AstraZeneca added that the trend did not reach statistical significance.
The trial—called Acute Stroke Or Transient IsChaemic Attack TReated with Aspirin or Ticagrelor and Patient OutcomES (SOCRATES)—was designed to assess the efficacy of Brilinta/Brilique 90-mg tablets twice daily, compared to aspirin 100 mg once daily in patients 40 years of age or older with an acute ischemic stroke or transient ischemic attack, with symptom onset within 24 hours.
SOCRATES assessed 13,600 patients in 33 countries.
“We will present the full analysis of the trial results, including subgroups, at a forthcoming stroke congress and will engage with regulatory agencies on the interpretation of the data,” Sean Bohen, AstraZeneca’s evp, global medicines development and CMO, said in a statement.
Ticagrelor is marketed as Brilinta in the U.S. and as Brilique elsewhere in the world. Brilinta/Brilique is a direct-acting P2Y12 receptor antagonist designed to work by inhibiting platelet activation.
The SOCRATES trial failure dents AstraZeneca’s hopes of raising Brilinta/Brilique sales from $619 million reported for last year (up 44% from 2014) to $3.5 billion by 2023—a chunk of the $45 billion in annual revenues projected for that year by the company when it successfully fought a takeover attempt by Pfizer in 2014.
“It's a setback but at this stage we are not providing any new guidance on the overall ($3.5 billion) number,” Ludovic Helfgott, head of AstraZeneca's Brilinta business, told Reuters.
The SOCRATES trial is part of PARTHENON, the largest ever AstraZeneca cardiovascular disease clinical program, involving nearly 80,000 patients at high risk of cardiovascular events. Data is expected in the second half of this year from another PARTHENON-related trial, EUCLID, assessing Brilinta/Brilique in patients with peripheral arterial disease, the company said. Other trials are in progress involving the drug in patients with coronary artery disease (PEGASUS-TIMI 54) and patients with type 2 diabetes at high risk of cardiovascular events (THEMIS).
Bohen added that the SOCRATES trial enrolled a patient population that differed from those for which Brilinta/Brilique is now indicated.
Brilinta/Brilique 90 mg is indicated to reduce the rate of thrombotic cardiovascular events in patients with acute coronary syndromes (ACS)—unstable angina (UA), non–ST-elevation myocardial infarction, or ST-elevation myocardial infarction. Brilinta/Brilique 60 mg is indicated for patients who have suffered a heart attack at least 1 year earlier and are at high risk of developing a further atherothrombotic event. Treatment with Brilinta/Brilique 60 mg may be started as continuation therapy after an initial 1-year treatment with Brilinta/Brilique 90 mg and aspirin or other dual antiplatelet therapy.
