New Formulation Provides Effective Treatment for Patients with Cholesterol, Triglyceride and other Lipid Disorders
EAST HANOVER, New Jersey - Novartis Pharmaceuticals Corporation today announced approval by the U.S. Food and Drug Administration for LESCOL® XL (fluvastatin sodium) 80 mg, an extended-release tablet formulation of fluvastatin, a therapy that provides effective management of all major lipid parameters for patients with a variety of lipid disorders that place them at risk for heart disease. Phase III clinical trials demonstrate that LESCOL XL 80 mg produced up to 38 percent median decrease in low-density lipoprotein cholesterol (LDL-C) in patients with dyslipidemia, and a 25 percent median decrease in triglycerides (TG) and a 13 percent mean increase in high-density lipoprotein cholesterol (HDL-C) in patients with primary mixed dyslipidemia (Fredrickson Type IIb), as compared with LESCOL® (fluvastatin sodium) 40 mg therapy.
"Physicians can use LESCOL XL as a starting dose to help patients effectively manage all major lipid parameters," said Paulo Costa, president and chief executive officer, Novartis Pharmaceuticals Corporation. "Phase III data demonstrate that this new formulation has the potential to bring the majority of patients who require statin therapy to their treatment goals."
For patients who have lipid disorders that place them at risk for heart disease, more than 90 percent can meet their treatment goals, as defined by the clinical application of the National Cholesterol Education Program (NCEP), by achieving a reduction of less than 30 percent in their LDL-C levels, according to empirical data from the National Health and Nutrition Examination Survey (NHANES III). The National Heart, Lung, and Blood Institute created the NCEP to contribute to reducing illness and death from coronary heart disease in the United States by reducing the percent of Americans with high blood cholesterol.
Statins block the enzymatic pathway for cholesterol synthesis in the liver. The reformulated extended-release LESCOL XL 80 mg tablet provides patients with a higher dose of medication, while maintaining safety. With this slow release delivery form of the drug, availability of the statin to the liver is increased while minimizing the risk of systemic exposure to high drug doses throughout the body.
In addition, fluvastatin is not predominantly metabolized by the cytochrome P450 3A4 pathway, thus minimizing the potential for interactions with drugs that patients commonly take on a daily basis that are metabolized through this pathway.
LESCOL XL 80 mg, as recommended as a starting dose, is indicated as an adjunct to diet to reduce patients' elevated total cholesterol, LDL-C, TG and apolipoprotein B (Apo B) levels, and to increase HDL-C in patients with primary hypercholesterolemia and mixed dyslipidemia and to slow the progression of atherosclerosis in patients with coronary heart disease. LESCOL XL 80 mg also has been approved by health authorities in Austria, Brazil, Portugal, Switzerland, Thailand, and the United Kingdom.
The FDA approved LESCOL XL 80mg based on their review of data from five controlled clinical trials that were four to 24 weeks in duration in more than 900 patients with Type IIa or IIb hyperlipoproteinemia. A pooled analysis of three pivotal trials that were 24 weeks in duration showed median LDL-C reductions ranging from 35-38 percent in patients with dyslipidemia. LESCOL XL 80 mg produced a median reduction in TG of 19 percent in patients with dyslipidemia and 25 percent in patients with primary mixed dyslipidemia (Fredrickson Type IIb). In addition, LESCOL XL 80 mg produced HDL-C increases ranging from 0-15 percent (25th -75th percentile: median 7 percent) in patients with dyslipidemia and increases ranging from 3-20 percent (25th -75th percentile: median 11 percent) in patients with primary mixed dyslipidemia (Fredrickson Type IIb). These trials confirmed that a daily dose regimen of LESCOL XL 80 mg provides significantly improved efficacy with a similar safety profile when compared to LESCOL 40 mg.
The current formulation of LESCOL is marketed in more than 90 countries worldwide as an adjunct to diet and exercise for the treatment of elevated total cholesterol, LDL-C, TG and Apo B in patients with primary hypercholesterolemia and mixed dyslipidemia and to slow the progression of atherosclerosis in patients with coronary heart disease. LESCOL has been studied in more than 25,000 patients.
In clinical trials with LESCOL, adverse events were generally mild and similar to placebo. Common adverse events were fatigue, nausea, diarrhea, dyspepsia, abdominal pain and rash. In Phase III clinical trials, the overall incidence of adverse events for LESCOL XL was similar to LESCOL 40 mg, and no cases of myopathy or rhabdomyolysis were observed in these trials.
LESCOL and LESCOL XL should not be used by pregnant or nursing women, in patients who currently have liver disease or unexplained increases in liver enzyme levels, and in patients who are allergic to any ingredient in this medication. It is recommended that liver function tests be performed before the initiation of therapy and at 12 weeks following initiation of treatment or elevation in dose. If serum transaminase levels rise, monitor more often; if they persist at three or more times the upper limit of normal, discontinue LESCOL or LESCOL XL. Treatment with LESCOL and LESCOL XL should be discontinued if myopathy or rhabdomyolysis are diagnosed or suspected. The effect of LESCOL or LESCOL XL on cardiovascular morbidity and mortality has not been determined.
For full LESCOL prescribing information, contact Anna Frable, Novartis Pharmaceuticals Corporation, 59 Route 10, East Hanover, NJ 07936, (973) 781-5388 or via the internet at anna.frable@pharma.novartis.com.
Novartis Pharmaceuticals Corporation researches, develops, manufactures and markets leading innovative prescription drugs used to treat a number of diseases and conditions, including central nervous system disorders, organ transplantation, cardiovascular diseases, dermatological diseases, respiratory disorders, cancer and arthritis. The company's mission is to improve people's lives by pioneering novel healthcare solutions.
Located in East Hanover, New Jersey, Novartis Pharmaceuticals Corporation is an affiliate of the Novartis Group (NYSE: NVS), a world leader in healthcare with core businesses in pharmaceuticals, consumer health, generics, eye-care, and animal health. In 1999, the Group (including Agribusiness) achieved sales of USD 21.7 billion and invested more than USD 2.8 billion in R&D. Headquartered in Basel, Switzerland, Novartis employs about 82,400 people and operates in over 140 countries around the world. The Group plans to spin off its Crop Protection and Seeds sectors and to merge them with the agrochemicals business of AstraZeneca in the fourth quarter of 2000.