WILMINGTON, Del.--(BUSINESS WIRE)--AstraZeneca today announced the US Food and Drug Administration (FDA) has accepted a supplemental New Drug Application (sNDA) and granted Priority Review for BRILINTA (ticagrelor) for the reduction of subsequent stroke in patients who experienced an acute ischemic stroke or transient ischemic attack (TIA).
The Prescription Drug User Fee Act date, the FDA action date for this supplemental application, is scheduled for the fourth quarter of 2020.
The sNDA was based on results from the Phase III THALES trial, which showed aspirin plus BRILINTA 90mg used twice daily for 30 days, resulted in a statistically significant and clinically meaningful reduction in the risk of the primary composite endpoint of stroke and death, compared to aspirin alone.1 The results were in line with the known safety profile of BRILINTA.1
Mene Pangalos, Executive Vice President, BioPharmaceuticals R&D, said: “Patients who have had an acute ischemic stroke or transient ischemic attack are at high risk of experiencing a subsequent stroke, which may be disabling or fatal. Today’s Priority Review reflects BRILINTA’s potential as a much-needed treatment option to reduce the rate of subsequent stroke for these patients and we look forward to working with the FDA to make BRILINTA available as soon as possible.”
The data from the THALES trial will be published in a peer-reviewed journal and presented at an forthcoming medical congress.
BRILINTA is not indicated in patients with minor acute ischemic stroke or high-risk transient ischemic attack.
BRILINTA is approved in more than 110 countries for the prevention of atherothrombotic events in adult patients with acute coronary syndrome (ACS) and in more than 70 countries for the secondary prevention of cardiovascular events among high-risk patients who have experienced a heart attack. In May 2020, the Food and Drug Administration (FDA) approved a label update for BRILINTA in the US to include the reduction of the risk of a first heart attack or stroke in high-risk patients with coronary artery disease.
BRILINTA is indicated to reduce the risk of cardiovascular death, myocardial infarction (MI), and stroke in patients with acute coronary syndrome (ACS) or a history of myocardial infarction. For at least the first 12 months following ACS, it is superior to clopidogrel. BRILINTA also reduces the risk of stent thrombosis in patients who have been stented for treatment of ACS.
BRILINTA is indicated to reduce the risk of a first MI or stroke in patients with coronary artery disease (CAD) at high risk for such events. While use is not limited to this setting, the efficacy of ticagrelor was established in a population with type 2 diabetes.
In the management of ACS, initiate BRILINTA treatment with a 180-mg loading dose. Administer 90 mg twice daily during the first year after an ACS event. After one year administer 60 mg twice daily.
In patients with CAD but no prior stroke or MI, administer 60 mg twice daily.
Use BRILINTA with a daily maintenance dose of aspirin of 75-100 mg.
IMPORTANT SAFETY INFORMATION FOR BRILINTA® (ticagrelor) 60-MG AND 90-MG TABLETS
A. BLEEDING RISK
- BRILINTA, like other antiplatelet agents, can cause significant, sometimes fatal bleeding
- Do not use BRILINTA in patients with active pathological bleeding or a history of intracranial hemorrhage
- Do not start BRILINTA in patients undergoing urgent coronary artery bypass graft surgery
- If possible, manage bleeding without discontinuing BRILINTA. Stopping BRILINTA increases the risk of subsequent cardiovascular events
B. ASPIRIN DOSE AND BRILINTA EFFECTIVENESS
- Maintenance doses of aspirin above 100 mg reduce the effectiveness of BRILINTA and should be avoided
- BRILINTA is contraindicated in patients with a history of intracranial hemorrhage or active pathological bleeding such as peptic ulcer or intracranial hemorrhage. BRILINTA is also contraindicated in patients with hypersensitivity (eg, angioedema) to ticagrelor or any component of the product.
WARNINGS AND PRECAUTIONS
- Dyspnea was reported more frequently with BRILINTA than in patients treated with control agents. Dyspnea from BRILINTA is often self-limiting
- Discontinuation of BRILINTA will increase the risk of MI, stroke, and death. When possible, interrupt therapy with BRILINTA for 5 days prior to surgery that has a major risk of bleeding. If BRILINTA must be temporarily discontinued, restart as soon as possible
- Ticagrelor can cause ventricular pauses. Bradyarrhythmias including AV block have been reported in the post-marketing setting. Clinical trials excluded patients at increased risk of bradyarrhythmias not protected by a pacemaker, and they may be at increased risk of developing bradyarrhythmias
- Avoid use of BRILINTA in patients with severe hepatic impairment. Severe hepatic impairment is likely to increase serum concentration of ticagrelor and there are no studies of BRILINTA in these patients
- In patients with Heparin Induced Thrombocytopenia (HIT): False negative results for HIT-related platelet functional tests, including the heparin-induced platelet aggregation (HIPA) assay, have been reported with BRILINTA. BRILINTA is not expected to impact PF4 antibody testing for HIT
- The most common adverse reactions (>5%) associated with the use of BRILINTA included bleeding and dyspnea
- Avoid use with strong CYP3A inhibitors and strong CYP3A inducers. BRILINTA is metabolized by CYP3A4/5. Strong inhibitors substantially increase ticagrelor exposure and so increase the risk of adverse events. Strong inducers substantially reduce ticagrelor exposure and so decrease the efficacy of ticagrelor
- As with other oral P2Y12 inhibitors, co-administration of opioid agonists delay and reduce the absorption of ticagrelor. Consider use of a parenteral anti-platelet in ACS patients requiring co-administration
- Patients receiving more than 40 mg per day of simvastatin or lovastatin may be at increased risk of statin-related adverse events
- Monitor digoxin levels with initiation of, or change in, BRILINTA therapy
- Lactation: Breastfeeding not recommended
Please read full Prescribing Information, including Boxed WARNINGS, and Medication Guide.
Stroke is the second leading cause of death worldwide, with 6.2 million stroke-related deaths in 2017, from which 2.7 million were due to ischemic stroke.2 Patients who experience an acute ischemic stroke or TIA are at high risk of developing subsequent ischemic events, with particularly high risk within 30 days after the initial event and the highest risk period being the first 24 hours after the initial event.3
THALES is an AstraZeneca-sponsored, randomized, placebo-controlled, double-blinded, international, multicenter, event-driven trial involving more than 11,000 patients from 28 countries. It tested the hypothesis whether aspirin plus BRILINTA is superior to aspirin alone in preventing the composite of stroke and death in patients with non-cardioembolic minor acute ischemic stroke or high-risk TIA. Patients were randomized within 24 hours of onset of acute ischemic stroke or high-risk TIA symptoms and followed-up for 30 days of treatment. Trial treatments were BRILINTA 180mg loading dose on day 1 as soon as possible after randomization, followed by 90mg twice daily on days 2-30, or matching placebo. All patients received open-label aspirin 300-325mg on day 1, followed by 75-100mg once daily on days 2-30. The primary efficacy outcome was the time to the composite endpoint of stroke and death at 30 days. The primary safety outcome is time to first severe bleeding event according to the Global Utilization of Streptokinase and Tissue Plasminogen Activator for Occluded Coronary Arteries (GUSTO) definition, which includes fatal bleedings, intracranial hemorrhage; and bleeding causing hemodynamic compromise requiring intervention. Patients were followed for an additional 30 days on standard of care.
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- AstraZeneca: https://otp.tools.investis.com/clients/uk/astrazeneca/rns/regulatory-story.aspx?cid=1343&newsid=1361096.
- Roth GA et al. Global, regional, and national age-sex-specific mortality for 282 causes of death in 195 countries and territories, 1980–2017: A systematic analysis for the Global Burden of Disease Study 2017. The Lancet 2018; 392(10159):1736–88.
- Khanevski AN, et al. Thirty-day recurrence after ischemic stroke or TIA. Brain Behav 2018; 8(10):e01108.