WILMINGTON, Del., Dec. 11 Today, the U.S. Food and Drug Administration (FDA) posted briefing materials in advance of the December 15(th) Endocrinologic and Metabolic Drugs Advisory Committee (EMDAC) to discuss the supplemental New Drug Application (sNDA) filed by AstraZeneca (NYSE: AZN). The briefing materials can be found on the FDA web site.
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In July, AstraZeneca announced that it had filed an sNDA with the FDA which seeks to incorporate outcomes data from the JUPITER study into the CRESTOR(®) (rosuvastatin calcium) Prescribing Information. As noted in the FDA briefing materials, the sNDA filed by AstraZeneca includes a proposed draft indication based on the JUPITER study as follows:
"For the prevention of cardiovascular disease in adult patients with an increased risk of cardiovascular disease based on the presence of cardiovascular disease risk markers such as an elevated hsCRP level, age, hypertension, low HDL-C, smoking or a family history of premature coronary heart disease, CRESTOR is indicated to:
Although included in the FDA briefing materials, the Advisory Committee is not expected to vote on the indication proposed by AstraZeneca.
According to the FDA briefing materials, the FDA Advisory Committee will vote on whether there is sufficient evidence of a favorable benefit-to-risk profile for rosuvastatin for the primary prevention of CVD in middle and older aged low-to-moderate cardiovascular disease (CVD) risk individuals with levels of LDL-C <130 mg/dL and hsCRP greater than or equal to 2 mg/L. The FDA Advisory Committee will also discuss three non-voting questions related to imbalances in gastrointestinal-related deaths and confusional state as well as the investigator-reported diabetes as observed in JUPITER.
AstraZeneca looks forward to presenting and discussing the data on December 15(th) and to continuing to work with the FDA to progress the sNDA towards the approval of an indication that supports the appropriate use of CRESTOR on the basis of this data.
In adults, CRESTOR is prescribed along with diet for lowering high cholesterol. CRESTOR is also prescribed along with diet to slow the progression of atherosclerosis (the build-up of plaque in arteries) as part of a treatment plan to lower cholesterol to goal. The approved indications are not scheduled to be part of the discussion at the upcoming meeting.
Results from the primary analysis of 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 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.
-- reduce the risk of total mortality -- reduce the risk of cardiovascular death -- reduce the risk of stroke -- reduce the risk of myocardial infarction -- reduce the risk of arterial revascularization -- reduce the risk of unstable angina"