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FDA Approves AstraZeneca PLC (AZN) Heart Drug Brilinta



7/20/2011 4:25:10 PM

WILMINGTON, Del., Jul 20, 2011 (BUSINESS WIRE) -- AstraZeneca AZN +1.21% announced today that the US Food and Drug Administration (FDA) has approved BRILINTA(TM) (ticagrelor) tablets to reduce the rate of heart attack (myocardial infarction [MI]) and cardiovascular (CV) death in adult patients with acute coronary syndrome (ACS), compared to clopidogrel.

BRILINTA, a new oral antiplatelet medicine, is indicated to reduce the rate of thrombotic cardiovascular events in patients with ACS (unstable angina [UA] non-ST-elevation myocardial infarction [NSTEMI], or ST-elevation myocardial infarction [STEMI]). BRILINTA has been shown to reduce the rate of a combined endpoint of CV death, MI or stroke compared to clopidogrel. The difference between treatments was driven by CV death and MI with no difference in stroke. In patients treated with an artery-opening procedure known as percutaneous coronary intervention (PCI), BRILINTA reduces the rate of stent thrombosis. BRILINTA has been studied in ACS in combination with aspirin. Maintenance doses of aspirin above 100 mg decreased the effectiveness of BRILINTA. Avoid maintenance doses of aspirin above 100 mg daily.

David Brennan, Chief Executive Officer, AstraZeneca said: "The FDA approval of BRILINTA is good news for patients in the United States and represents a significant milestone as we seek to help ensure ACS patients around the world have access to this innovative medicine. With over one million people affected by ACS in the US each year, 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."

Now that BRILINTA is approved in the US, AstraZeneca will begin the process of working with hospital formularies, protocol committees, government and managed care reimbursement bodies to bring this medicine to patients. Navigating these steps, which are necessary before BRILINTA will be available to a substantial number of incident ACS patients, will be a key focus for the next 12 months.

The FDA approval is based upon data from the landmark PLATO (A Study of PLATelet Inhibition and Patient Outcomes) study, a superiority trial that compared treatment with BRILINTA to clopidogrel in 18,624 ACS patients worldwide.

BRILINTA, like other antiplatelet agents, can cause significant, sometimes fatal, bleeding. In PLATO, there was no statistical difference in patients treated with BRILINTA compared to patients treated with clopidogrel in total major bleeding events (11.6% vs. 11.2%), including fatal and fatal/life-threatening bleeding events.(2) Non-CABG (coronary artery bypass graft) major + minor bleeding events (8.7% vs. 7%) were more common with BRILINTA versus clopidogrel.

The most commonly observed adverse reactions associated with the use of BRILINTA vs. clopidogrel were bleeding (11.6% vs.11.2%) and a feeling of breathlessness called dyspnea (14% vs. 8%).

As with all AstraZeneca products, the company will work to ensure that physicians and patients understand both the benefits and risks associated with BRILINTA. For BRILINTA, one of the ways AstraZeneca will help ensure physicians and patients are appropriately informed about bleeding risk and the impact of aspirin dose on the effectiveness of BRILINTA is through a Risk Evaluation Mitigation Strategy (REMS).

According to the American Heart Association, over one million Americans are hospitalized with ACS every year. It is estimated that up to one in three patients could have a recurrent heart attack, or die within one year of their first CV event.(1)

BRILINTA is now approved in 39 countries, including the US, Brazil, Australia, and Canada under the trade name BRILINTA and in the European Union under the trade name BRILIQUE(TM). BRILINTA is currently under regulatory review in an additional 45 countries, including Russia, India and China. BRILINTA is currently reimbursed in 7 countries.

ABOUT PLATO

PLATO was a large (18,624 patients in 43 countries) head-to-head patient outcomes study of ticagrelor versus clopidogrel, both given in combination with aspirin and other standard therapy, designed to establish whether ticagrelor could achieve a clinically meaningful reduction in cardiovascular end points in ACS patients, above and beyond those afforded by clopidogrel.

The study demonstrated that treatment with BRILINTA led to a greater reduction in the primary end point -- a composite of CV death, MI, or stroke -- compared to patients who received clopidogrel (9.8% vs. 11.7% at 12 months; 1.9% absolute risk reduction [ARR]; 16% relative risk reduction [RRR]; 95% CI, 0.77 to 0.92; P<0.001). The difference in treatments was driven by CV death and MI with no difference in stroke. In PLATO, the absolute difference in treatment benefit versus clopidogrel was seen at 30 days and the Kaplan-Meier survival curves continue to diverge throughout the 12 month treatment period.

The study also demonstrated that treatment with BRILINTA for 12 months was associated with a 21 percent RRR in CV death (4% vs. 5.1%; 1.1% ARR; P=0.001) and a 16 percent RRR in MI compared to clopidogrel at 12 months (5.8% vs. 6.9%; 1.1% ARR; P<0.005).

In a post hoc analysis of PLATO, it was determined that more than 80 percent of patients worldwide, including more than 40 percent of patients in the US, received low maintenance doses of aspirin (100 mg or less). Results for US and non-US patients taking BRILINTA with these low maintenance doses of aspirin were similar. Maintenance doses of aspirin above 100 mg reduced the effectiveness of BRILINTA, and should be avoided. After any initial dose, BRILINTA should be used with maintenance aspirin doses of 75-100 mg per day. As with any unplanned subset analysis, the post hoc analysis should be treated with caution.

IMPORTANT SAFETY INFORMATION ABOUT BRILINTA (TICAGRELOR) TABLETS

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 planned to undergo urgent coronary artery bypass graft surgery (CABG). When possible, discontinue BRILINTA at least 5 days prior to any surgery.

Suspect bleeding in any patient who is hypotensive and has recently undergone coronary angiography, percutaneous coronary intervention (PCI), CABG, or other surgical procedures in the setting of BRILINTA.

If possible, manage bleeding without discontinuing BRILINTA. Stopping BRILINTA increases the risk of subsequent cardiovascular events.

ASPIRIN DOSE AND BRILINTA EFFECTIVENESS

Maintenance doses of aspirin above 100 mg reduce the effectiveness of BRILINTA and should be avoided. After any initial dose, use with aspirin 75-100 mg per day.

Risk factors for bleeding include older age, a history of bleeding disorders, performance of percutaneous invasive procedures and concomitant use of medications that increase the risk of bleeding.

If BRILINTA must be temporarily discontinued, it should be restarted as soon as possible.

The use of BRILINTA is also contraindicated in severe hepatic impairment. BRILINTA has not been studied in patients with moderate hepatic impairment. Consider the risks and benefits of treatment, noting the probable increase in exposure to ticagrelor.

Dyspnea was reported in 14% of patients treated with BRILINTA and in 8% of patients treated with clopidogrel. If dyspnea is determined to be related to BRILINTA, no specific treatment is required; continue BRILINTA without interruption.

BRILINTA is metabolized by CYP3A4/5. Avoid use with strong CYP3A inhibitors and potent CYP3A inducers.

Avoid simvastatin and lovastatin doses greater than 40 mg. BRILINTA will result in higher serum concentrations of simvastatin and lovastatin because these drugs are metabolized by CYP3A4.

Monitor digoxin levels with initiation of or any change in BRILINTA therapy, because of inhibition of the P-glycoprotein transporter.

There is limited clinical experience in patients at increased risk of symptomatic bradycardic events. In PLATO, syncope, pre-syncope and loss of consciousness were reported by 1.7% and 1.5% of BRILINTA and clopidogrel patients, respectively. In a Holter substudy of about 3,000 patients in PLATO, more patients had ventricular pauses with BRILINTA (6%) than with clopidogrel (3.5%), in the acute phase; rates were 2.2% and 1.6% respectively after one month.

The most commonly observed adverse reactions associated with the use of BRILINTA vs. clopidogrel were bleeding (11.6% vs.11.2%) and dyspnea (14% vs. 8%).

Please see full US Full Prescribing Information including BOXED WARNINGS and Medication Guide at www1.astrazeneca-us.com/pi/brilinta.pdf .

NOTES TO EDITORS:

About BRILINTA (ticagrelor)

BRILINTA is an oral antiplatelet treatment for acute coronary syndrome (ACS) in a new chemical class called cyclopentyltriazolopyrimidines (CPTPs). BRILINTA works by preventing the formation of new blood clots and maintaining blood flow in the body to help reduce a patient's risk of another cardiovascular event (called atherothrombotic events) such as a heart attack or cardiovascular death. BRILINTA is a reversibly-binding oral adenosine diphosphate (ADP) receptor antagonist.

BRILINTA will be available in 90 mg tablets to be administered with a single 180 mg oral loading dose (two 90 mg tablets) followed by a twice daily, 90 mg maintenance dose. Following an initial loading dose of aspirin, BRILINTA should be used with a maintenance dose of 75-100 mg aspirin once daily; for most patients an 81 mg aspirin dose is likely to be used.

BRILINTA and BRILIQUE are trademarks of the AstraZeneca group of companies.

About Acute Coronary Syndrome (ACS)

ACS is an umbrella term for conditions that result from insufficient blood supply to the heart muscle. These conditions range from unstable angina (unremitting chest pain that threatens a heart attack) to heart attack.

About AstraZeneca

AstraZeneca is a global, innovation-driven biopharmaceutical business with a primary focus on the discovery, development and commercialization of prescription medicines for gastrointestinal, cardiovascular, neuroscience, respiratory and inflammation, oncology and infectious disease. AstraZeneca operates in over 100 countries and its innovative medicines are used by millions of patients worldwide.

For more information about AstraZeneca in the US or our AZ&Me(TM) Prescription Savings programs, please visit: www.astrazeneca-us.com or call 1-800-AZandMe (292-6363).

References

(1)Roger, Go, Lloyd-Jones, et al. Heart Disease and Stroke Statistics2011 Update: A Report From the American Heart Association. Circulation 2011;123;e18-e209. (2)Wallentin, Becker, Budaj, et al Ticagrelor versus Clopidogrel in Patients with Acute Coronary Syndromes. N Engl J Med 2009;361:1045-57.

Photos/Multimedia Gallery Available: http://www.businesswire.com/cgi-bin/mmg.cgi?eid=6801457&lang=en

SOURCE: AstraZeneca

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