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Genzyme and Isis Present KYNAMRO® Clinical Data at the American Heart AssociationCAMBRIDGE, Mass. & CARLSBAD, Calif. --(Business Wire)-- Genzyme, a Sanofi company, and Isis Pharmaceuticals Inc. (NASDAQ: ISIS), today announced that new two-year data from a phase 3 long-term extension study of KYNAMRO® (mipomersen sodium) injection was presented at a scientific session at the annual American Heart Association meeting in Chicago, IL. In the study, a retrospective analysis showed that patients treated with KYNAMRO for a mean of two years had a significant reduction in Major Adverse Cardiovascular Events (MACE) compared to two years prior to therapy. "This analysis is very encouraging as the rate of MACE declined sevenfold after two years of treatment with KYNAMRO in patients with homozygous and heterozygous familial hypercholesterolemia (FH)," said Dr. John Kastelein, M.D., Ph.D., professor of medicine, chairman of the department of vascular medicine, Academic Medical Center, University of Amsterdam. "This analysis represents an important finding and supports the potential for further study of the therapeutic benefit of KYNAMRO in patients." This retrospective analysis included 104 patients who enrolled in the long-term extension study of KYNAMRO after having completed one of the KYNAMRO phase 3 blinded, randomized, placebo-controlled 6-month trials in patients with homozygous and heterozygous FH. All patients who completed at least two years of treatment with KYNAMRO were included in the analysis. The rate of MACE in patients treated with KYNAMRO for two years were adjudicated by an independent committee and compared to the rate of MACE in the same patients based on their medical history prior to treatment with KYNAMRO. In this analysis, MACE were identified in 62% of patients during two years prior to KYNAMRO treatment, and 9% of patients during a mean of 24.4 months after initiation of treatment with KYNAMRO. MACE were defined as myocardial infarction (MI), stroke, unstable angina (UA) and revascularization procedures (PCI (News - Alert)/CABG).
The marked reduction in MACE coincided with the absolute mean reductions in LDL cholesterol levels (-49 to -113 mg/dL) reported for the phase 3 FH clinical trials. "Patients with homozygous FH have extreme cholesterol levels and are at significant risk for cardiovascular events. KYNAMRO is approved for use in these patients in the U.S. to reduce LDL-cholesterol, apoB, total cholesterol and non-HDL cholesterol as an adjunct to lipid lowering medication and diet. The data presented today are encouraging and add to the broad lipid lowering profile observed in these patients," said Dr. Sotirios Tsimikas, M.D., professor of medicine and director of vascular medicine at the University of California, San Diego and vice president of clinical development and leader of the cardiovascular franchise at Isis. KYNAMRO contains a Boxed Warning citing the risk of hepatic toxicity. Patients taking KYNAMRO should have liver enzyme testing before starting the drug and periodically thereafter. See below for Important Safety Information about KYNAMRO. The safety and effectiveness of KYNAMRO have not been established in patients with hypercholesterolemia who do not have HoFH. The effect of KYNAMRO on cardiovascular morbidity and mortality has not been determined. Because of the risk of hepatotoxicity, KYNAMRO is available only through a Risk Evaluation and Mitigation Strategy (REMS) called the KYNAMRO REMS. The goals of the KYNAMRO REMS are:
IMPORTANT SAFETY INFORMATION WARNING: RISK OF HEPATOTOXICITY KYNAMRO can cause elevations in transaminases. In the KYNAMRO clinical trial in patients with HoFH, 4 (12%) of the 34 patients treated with KYNAMRO compared with 0% of the 17 patients treated with placebo had at least one elevation in alanine aminotransferase (ALT) =3x upper limit of normal (ULN). There were no concomitant clinically meaningful elevations of total bilirubin, international normalized ratio (INR) or partial thromboplastin time (PTT). KYNAMRO also increases hepatic fat, with or without concomitant increases in transaminases. In the trials in patients with heterozygous familial hypercholesterolemia (HeFH) and hyperlipidemia, the median absolute increase in hepatic fat was 10% after 26 weeks of treatment, from 0% at baseline, measured by magnetic resonance imaging (MRI). Hepatic steatosis is a risk factor for advanced liver disease; including steatohepatitis and cirrhosis. Measure ALT, AST, alkaline phosphatase, and total bilirubin before initiating treatment and then ALT, AST regularly as recommended. During treatment, withhold the dose of KYNAMRO if the ALT or AST are =3x ULN. Discontinue KYNAMRO for clinically significant liver toxicity. Because of the risk of hepatotoxicity, KYNAMRO is available only through a restricted program under a Risk Evaluation and Mitigation Strategy (REMS) called the KYNAMRO REMS. CONTRAINDICATIONS KYNAMRO is contraindicated in the following conditions:
WARNINGS AND PRECAUTIONS KYNAMRO can cause elevations in transaminases and hepatic steatosis. Prior to initiation of treatment with KYNAMRO, measure a full liver panel to include ALT, AST, total bilirubin, and alkaline phosphatase. If the baseline liver-related tests are abnormal, consider initiating KYNAMRO after an appropriate work-up and the baseline abnormalities are explained or resolved. During the first year, conduct liver-related tests monthly (ALT and AST, at a minimum). After the first year, conduct these tests at least every 3 months. Discontinue KYNAMRO for persistent or clinically significant elevations. If transaminase elevations are accompanied by clinical symptoms of liver injury (e.g., nausea, vomiting, abdominal pain, fever, jaundice, lethargy, flu-like symptoms), increases in bilirubin =2x ULN, or active liver disease, discontinue treatment with KYNAMRO and identify the probable cause. Alcohol may increase levels of hepatic fat and induce or exacerbate liver injury. It is recommended that patients taking KYNAMRO should consume no more than one alcoholic drink per day. Caution should be exercised when KYNAMRO is used with other medications known to have potential for hepatotoxicity, for example isotretinoin, amiodarone, acetaminophen (>4 g/day for =3 days/week), methotrexate, tetracyclines, and tamoxifen. The effect of concomitant administration of KYNAMRO with other hepatotoxic medications is unknown. More frequent monitoring of liver-related tests may be warranted. KYNAMRO has not been studied concomitantly with other LDL-lowering agents that can also increase hepatic fat. Therefore, the combined use of such agents is not recommended. Injection site reactions have been reported in 84% of patients receiving KYNAMRO therapy. These local reactions typically consist of one or more of the following: erythema, pain, tenderness, pruritus and local swelling. To minimize the potential for injection site reactions, proper technique for subcutaneous administration should be followed. Injection site reactions do not occur with all injections but resulted in discontinuation of therapy in 5% of patients in pooled Phase 3 trials. Flu-like symptoms have been reported in 30% of patients receiving KYNAMRO therapy and include one or more of the following: influenza-like illness, pyrexia, chills, myalgia, arthralgia, malaise or fatigue. Flu-like symptoms, which typically occur within 2 days after an injection, do not occur with all injections but resulted in discontinuation of therapy in 3% of patients in pooled Phase 3 trials. USE IN SPECIFIC POPULATIONS Pregnancy Category B: There are no adequate and well-controlled studies in pregnant women. KYNAMRO should be used during pregnancy only if clearly needed. Nursing Mothers: It is not known whether KYNAMRO is excreted in human milk. Because many drugs are excreted in human milk a decision should be made whether to discontinue nursing or discontinue the drug, taking into account the importance of the drug to the mother. Pediatric Use: Safety and effectiveness have not been established in pediatric patients. Females of Reproductive Potential: KYNAMRO may cause fetal harm. Females who become pregnant during KYNAMRO therapy should notify their healthcare provider. Females of reproductive potential should use effective contraception during KYNAMRO therapy. Renal Impairment: The safety and efficacy of KYNAMRO treatment in patients with known renal impairment or in patients undergoing renal dialysis have not been established. Due to the lack of clinical data and KYNAMRO's renal safety profile, KYNAMRO is not recommended in patients with severe renal impairment, clinically significant proteinuria, or on renal dialysis. ADVERSE REACTIONS In clinical trials the most commonly-reported adverse reactions were injection site reactions (84%), flu-like symptoms (30%), nausea (14%), headache (12%), and elevations in serum transaminases, specifically ALT (10%). See full Prescribing Information and Medication Guide, including Boxed Warning, for more details.
About KYNAMRO® (mipomersen sodium) injection
About Homozygous Familial Hypercholesterolemia (HoFH)
About Genzyme, a Sanofi Company
About Sanofi
About Isis Pharmaceuticals, Inc. Isis Pharmaceuticals® is a registered trademark of Isis Pharmaceuticals, Inc. Genzyme® and KYNAMRO® are registered trademarks of Genzyme Corporation. All rights reserved.
Sanofi Forward Looking Statements
Isis Forward Looking Statement In this press release, unless the context requires otherwise, "Isis," "Company," "we," "our," and "us" refers to Isis Pharmaceuticals and its subsidiaries.
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