Brilique: Withdrawal of the application to change the marketing authorisation

Brilique is a medicine used together with aspirin to prevent problems caused by blood clots such as heart attacks or strokes (atherothrombotic events). It is used in adults with acute coronary syndrome, where blood flow in the vessels supplying the heart is blocked, causing problems such as heart attack and unstable angina (a severe type of chest pain). Brilique is also used in adults who had a heart attack at least a year ago and are at a high risk of an atherothrombotic event.

Brilique has been authorised in the EU since December 2010. It contains the active substance ticagrelor and is available as tablets.

The company applied for an extension of indication to add the use of Brilique, together with aspirin, to prevent stroke in adults who have had a mild to moderate acute ischaemic stroke (when a blood clot blocks the blood supply to part of the brain and causes a stroke) or high-risk TIA (when a blood clot temporarily blocks the blood supply to part of the brain, causing short-lasting stroke-like symptoms).

People who have had an acute ischaemic stroke or high-risk TIA may suffer disability and are at high risk of suffering a subsequent stroke in the period immediately after the event, which may cause further disability or death.

The active substance in Brilique, ticagrelor, is an inhibitor of platelet aggregation. This means that it helps to prevent blood clots from forming. Blood clots form due to cell fragments in the blood called platelets aggregating (sticking together). Ticagrelor stops the platelets aggregating by blocking the action of a substance called adenosine diphosphate (ADP) when it attaches to the surface of the platelets. This stops the platelets clumping together, reducing the risk of a blood clot forming and helping to prevent a stroke or heart attack.

In the prevention of stroke in adults who have had an acute ischaemic stroke or TIA, Brilique is expected to work in the same way as it does in its existing uses.

The company presented the results of a study involving over 11,000 patients who had had a mild to moderate acute ischaemic stroke or a high-risk TIA. Patients were given either Brilique or placebo (a dummy treatment), both taken in combination with aspirin. The study looked at the number of patients who had a stroke or died after 30 days of treatment. The study also looked at the number of patients with disability, measured with a standard disability scale, after 30 days of treatment.

The application was withdrawn after the European Medicines Agency had evaluated the information from the company and had prepared questions for the company. After the Agency had assessed the company’s responses to the questions, there were still some unresolved issues.

Based on the review of the information and the company’s response to the Agency’s questions, at the time of the withdrawal, the Agency was of the opinion that the requested change to Brilique’s marketing authorisation to add the prevention of stroke in adults after an acute ischaemic stroke or TIA could not be granted.

The Agency was concerned that the benefits of short-term treatment with Brilique together with aspirin in preventing stroke in patients who have had an acute ischaemic stroke or TIA did not clearly outweigh the risks of fatal and non-fatal bleeding. In addition, the study did not show a reduction in disability.

Therefore, the Agency’s opinion was that the benefits of Brilique in the prevention of stroke in adults after an acute ischaemic stroke or TIA did not outweigh its risks.

In its letter notifying the Agency of the withdrawal of application, the company stated that the withdrawal was based on EMA’s request for further detailed analysis to justify the use of Brilique in the target population.