WILMINGTON, Del., Dec. 15 The U.S. Food and Drug Administration (FDA) Endocrinologic and Metabolic Drugs Advisory Committee (EMDAC) today voted 12 yes, 4 no, and 1 abstention that AstraZeneca has established sufficient benefit to offset the observed risks to support the use of CRESTORŪ (rosuvastatin calcium) in individuals meeting the following criteria:
The review, based on results of the JUPITER (Justification for the Use of statins in Prevention: an Intervention Trial Evaluating Rosuvastatin) study, is part of the FDA's evaluation of the supplemental New Drug Application (sNDA) filed by AstraZeneca in April 2009 to update the CRESTOR Prescribing Information with information about the impact of CRESTOR on reducing the risk of cardiovascular events.
"AstraZeneca welcomes the Advisory Committee's positive vote," said Howard Hutchinson, M.D., Chief Medical Officer, AstraZeneca. "Today's discussions will help guide our ongoing dialogue with the FDA regarding our request for an indication that supports the use of CRESTOR for the prevention of cardiovascular disease in patients with an increased risk of experiencing cardiovascular events."
The FDA Advisory Committee also discussed four non-voting items related to a range of other observations in JUPITER, including adverse events and whether the JUPITER trial identified an appropriate new target patient population.
The FDA frequently convenes advisory committee meetings to obtain independent expert guidance and opinions on clinical matters. While the FDA is not required to follow this guidance, the agency usually takes the advice into consideration when rendering its final decisions on pending applications and other public health matters.
Results from JUPITER (Justification for the Use of statins in Prevention: an Intervention Trial Evaluating Rosuvastatin) were originally presented in November 2008 at the American Heart Association's Annual Scientific Sessions, and published by the New England Journal of Medicine, evaluated the impact of rosuvastatin 20 mg on reducing CV events (combined risk of myocardial infarction, stroke, arterial revascularization, hospitalization for unstable angina, or death from CV causes).
JUPITER was a long-term, randomized, double-blind, placebo-controlled, large-scale study of 17,802 patients designed to determine if rosuvastatin 20 mg decreases the risk of myocardial infarction, stroke and other cardiovascular events in patients with LDL-C < 130 mg/dL but at increased cardiovascular risk as identified by age and elevated high-sensitivity C-reactive protein (hsCRP). The majority of patients had at least one other risk factor including hypertension, low HDL-C, family history of premature coronary heart disease (CHD) or smoking. hsCRP is a recognized marker of inflammation which is associated with an increased risk of atherosclerotic cardiovascular events.
JUPITER is a part of AstraZeneca's extensive GALAXY clinical trials program, designed to address important unanswered questions in statin research. Currently, more than 65,000 patients have been recruited from 55 countries worldwide to participate in the GALAXY Program.
ABOUT CRESTOR (ROSUVASTATIN CALCIUM):
CRESTOR is indicated as an adjunct to diet to reduce elevated Total-C, LDL-C, ApoB, non-HDL-C, and TG levels and to increase HDL-C in patients with primary hyperlipidemia and mixed dyslipidemia. CRESTOR is also indicated as an adjunct to diet to slow the progression of atherosclerosis in adult patients as part of a treatment strategy to lower Total-C and LDL-C to target levels. CRESTOR is not approved to reduce cardiovascular morbidity and mortality.
IMPORTANT SAFETY INFORMATION:
CRESTOR is contraindicated in patients with a known hypersensitivity to any component of this product, in patients with active liver disease, which may include unexplained persistent elevations of hepatic transaminase levels, in women who are pregnant or may become pregnant, and in nursing mothers.
Cases of myopathy and rhabdomyolysis with acute renal failure secondary to myoglobinuria have been reported with HMG-CoA reductase inhibitors, including CRESTOR. These risks can occur at any dose level, but are increased at the highest dose (40 mg).
CRESTOR should be prescribed with caution in patients with predisposing factors for myopathy (eg, age greater than or equal to 65 years, inadequately treated hypothyroidism, renal impairment). The risk of myopathy during treatment with CRESTOR may be increased with concurrent administration of some other lipid-lowering therapies (fibrates or niacin), gemfibrozil, cyclosporine, or lopinavir/ritonavir.
Therapy with CRESTOR should be discontinued if markedly elevated CK levels occur or myopathy is diagnosed or suspected. All patients should be advised to promptly report unexplained muscle pain, tenderness, or weakness, particularly if accompanied by malaise or fever. It is recommended that liver enzyme tests be performed before and at 12 weeks following both the initiation of therapy and any elevation of dose, and periodically (e.g., semiannually) thereafter. Should an increase in ALT or AST of >3 times ULN persist, reduction of dose or withdrawal of CRESTOR is recommended. CRESTOR should be used with caution in patients who consume substantial quantities of alcohol.
CRESTOR 40 mg should be used only for those patients not achieving their LDL-C goal with 20 mg. Patients initiating CRESTOR therapy or switching from another statin should begin treatment with CRESTOR at the appropriate starting dose.
In the controlled clinical trials database, the most common adverse reactions were headache (3.7%), myalgia (3.1%), abdominal pain (2.6%), asthenia (2.5%), and nausea (2.2%).
Please see accompanying full Prescribing Information. If you have any questions concerning CRESTOR, please contact AstraZeneca at 1-800-237-8898. CRESTOR is a registered trademark of the AstraZeneca group of companies.
AstraZeneca (NYSE: AZN) is engaged in the research, development, manufacturing and marketing of meaningful prescription medicines and in the supply of healthcare services. AstraZeneca is one of the world's leading pharmaceutical companies with global healthcare sales of $31.6 billion and is a leader in gastrointestinal, cardiovascular, neuroscience, respiratory, oncology and infectious disease medicines. In the United States, AstraZeneca is a $13.5 billion dollar healthcare business.
For more information about AstraZeneca in the US or our AZ&Me(TM) Prescription Savings programs, please visit: www.astrazeneca-us.com.
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-- Men greater than or equal to 50 years, women greater than or equal to 60 years; -- Fasting LDL < 130 mg/dL; hsCRP greater than or equal to 2.0 mg/L; Triglycerides <500 mg/dL; -- No prior history of cardiovascular or cerebrovascular events or coronary heart disease (CHD) risk equivalent as defined by NCEP ATP-III guidelines.