AstraZeneca is celebrating after finally getting the green light from US regulators for its bloodthinner Brilinta, a drug that is widely-viewed as vital to the Anglo-Swedish drugmaker's future success.

The US Food and Drug Administration has approved Brilinta (ticagrelor) to reduce cardiovascular death and heart attack in patients with acute coronary syndromes (ACS). The thumbs-up is based on data from the 18,624 patient-PLATO study which revealed that treatment with Brilinta led to a greater reduction in the primary endpoint – a composite of cardiovascular death, myocardial infarction or stroke – compared to patients who received Sanofi/Bristol-Myers Squibb's blockbuster Plavix (clopidogrel).

Boxed warning about high-aspirin dosage

Brilinta has been studied in combination with aspirin and, as expected, will come with a boxed warning that aspirin doses above 100mg per day decrease the effectiveness of the medication. Norman Stockbridge, director of the Division of Cardiovascular and Renal Products in the FDA’s Center for Drug Evaluation and Research, noted that in clinical trials, Brilinta was more effective than Plavix in preventing heart attacks and death, "but that advantage was seen with aspirin maintenance doses of 75 to 100mg once-daily".

Brilinta has been approved with a risk evaluation and mitigation strategy which will see AstraZeneca conduct "educational outreach" to doctors to alert them about the risk of using higher doses of aspirin.

The high-dose aspirin restriction could limit Brilinta's commercial opportunity but AstraZeneca chief executive David Brennan is delighted. He said the approval "represents a significant milestone" and noted that there are over one million people affected by ACS in the USA each year. He went on to say "the fact that physicians have a new and more effective treatment option than clopidogrel to help reduce the rate of heart attack and cardiovascular death in these patients is an important advance".

Tough path to approval in USA

Good news then for patients and great news for the company which has been under pressure to get new drugs approved to soften the severe impact of generic competition on a number of its key products. Brilinta was approved in the European Union in December, as Brilique, but approval has been far from straightforward across the Atlantic.

Last December, the FDA issued a complete response letter and requested additional analyses of data from PLATO, expressing concern about the difference in treatment effect observed in the US and non-US patient subsets. AstraZeneca responded, saying the difference "is most likely a reflection of an underlying interaction between ticagrelor and higher doses of aspirin".

The Brilinta green light is particularly welcome now, coming as it does a day after the FDA's Endocrinologic and Metabolic Drugs Advisory Committee voted 9-6 against recommending approval of dapagliflozin, a diabetes drug that has been co-developed with Bristol-Myers Squibb.