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Study Shows LIVALO(R) is not Affected by Co-Administration of Itraconazole

September 2, 2009

BARCELONA, Spain, Sept. 2 /PRNewswire/ — LIVALO (pitavastatin) may have the potential for fewer drug-drug interactions, versus other statins, as evidenced by a new study that evaluated the effects of itraconazole, an antifungal medication, on the pharmacokinetics of LIVALO in healthy volunteers. The data were presented by Kowa at the European Society of Cardiology (ESC) Congress in Barcelona, Spain.

Many statins currently prescribed in the United States, such as atorvastatin and simvastatin, are metabolized by the cytochrome P450 system, particularly through the 3A4 pathway. Strong inhibitors of this pathway, such as itraconazole and grapefruit juice, can influence drug exposure levels that may result in other clinical complications, such as hospitalizations due to severe muscle problems.(1)

“Many patients taking statins require additional medications to address other cardiovascular risk factors or comorbid diagnoses, which can result in drug-drug interactions and subsequent noncompliance,” said Peter P. Toth, M.D., Ph.D., Director of Preventive Cardiology, Sterling Rock Falls Clinic, Ltd. “While statins are the mainstay of dyslipidemia management, there is still an unmet need among these patients who take multiple medications. These data suggest that LIVALO is a clinically effective and well-tolerated statin that has less potential for these types of interactions.”

The open-label study was conducted to determine the potential pharmacokinetic interaction of itraconazole (200 mg), an antifungal agent that strongly inhibits CYP3A4, on the pharmacokinetics of LIVALO (4 mg). The secondary objective assessed the safety of LIVALO 4 mg with the addition of itraconazole. Eighteen healthy males (aged 18 to 55 years) received LIVALO 4 mg once daily on days 1 and 8, and itraconazole 200 mg once daily on days 5 to 9. The results of this study showed that itraconazole did not increase plasma concentrations of LIVALO or its main metabolite pitavastatin lactone, potentially reducing the incidence of adverse events.

Additionally, LIVALO was shown to be well tolerated both as monotherapy and when combined with itraconazole and was not associated with any moderate or severe adverse events or clinically relevant changes in laboratory, vital or physical signs or ECG. No subjects withdrew from the study.

“This study suggests that, compared with other commonly prescribed statins, LIVALO’s metabolic route may offer a favorable tolerability profile when administered with drugs that inhibit CYP3A4,” said Roger E. Morgan, M.D., Chief Medical Officer, Kowa Research Institute. “Combined with LIVALO’s safety and efficacy profile, the low incidence of drug-drug interactions represents a benefit in the long-term treatment of patients with dyslipidemia.”

These results support previous LIVALO studies showing that grapefruit juice did not have a significant effect on plasma concentrations (<15%).( )

About LIVALO

LIVALO(R) was approved by the U.S. Food and Drug Administration in August 2009 as an adjunctive therapy to diet to reduce elevated total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), apolipoprotein B (Apo B), triglycerides (TG), and to increase HDL-C in adult patients with primary hyperlipidemia or mixed dyslipidemia.

LIVALO is a fully synthetic and highly potent statin that differs from other, currently available statins in the United States in that it has a unique cyclopropyl group on the base structure. This cyclopropyl group contributes to a more effective inhibition of the HMG-CoA reductase enzyme to inhibit cholesterol production, and potentially affords greater LDL-C clearance and reduction of plasma cholesterol. Importantly, LIVALO is only minimally metabolized by the liver through the cytochrome P450 pathway, a common pathway for the metabolism of many other medications.

In pivotal Phase III trials, LIVALO effectively reduced LDL-C and improved other parameters of lipid metabolism in special patient populations, including the elderly, patients with diabetes and patients at higher cardiovascular risk. The overall safety and tolerability of LIVALO are consistent with other commonly prescribed statins.

Since its launch in Japan, South Korea, Thailand and China, LIVALO has been successfully used in these countries to treat primary hypercholesterolemia and combined dyslipidemia, and has accumulated millions of patient-years of exposure. It is frequently prescribed in these countries as first-line therapy for a broad range of patients, including the elderly, patients with diabetes and those whose treatment is complicated by concurrent disease and concomitant medications. Kowa also filed for approval of LIVALO in Europe in August 2008, using the decentralized authorization procedure.

About Dyslipidemia and Hypercholesterolemia

Dyslipidemia refers to abnormal levels of fatty substances in the blood, or a disorder of the production or breakdown process of lipoprotein. Dyslipidemia may be marked by an elevation of TC, LDL-C, and TG concentrations and a decrease in HDL-C in the blood. An elevated level of cholesterol in the blood is called hypercholesterolemia, commonly referred to as high cholesterol.

Dyslipidemia is well established as one of the strongest independent predictors of cardiovascular morbidity and mortality. Despite the availability of treatments in the United States, there is still a need for better control of and treatment for dyslipidemia. According to the American Heart Association, approximately one out of every three American adults has an LDL-C level of 130 mg/dL or higher, which is a major risk factor for coronary heart disease (CHD) and stroke. In addition, less than half of patients who qualify for any kind of lipid-modifying treatment( )for CHD risk reduction are receiving it, and only about( )one-third of patients who are on treatment are achieving their LDL-C( )goals.

About Kowa Company Ltd., Kowa Pharmaceuticals America, Inc. and Kowa Research Institute, Inc.

Kowa Company, Ltd. (KCL) is a privately held multinational company headquartered in Nagoya, Japan. Established in 1894, KCL is actively engaged in various manufacturing and commercial activities in the fields of pharmaceutical, life science, information technology, textiles, machinery and various consumer products. KCL’s pharmaceutical division is focused on cardiovascular therapeutics, with sales of the company’s flagship product, LIVALO, totaling $340 million (12% market share) in Japan during the 2008 fiscal year and expected to exceed $500 million in the near future.

Kowa Pharmaceuticals America, Inc. (KPA) is a specialty pharmaceutical company focused primarily in the area of cardiometabolic therapeutics. The company, started in 2001 as ProEthic Pharmaceuticals, Inc., was acquired by KCL in September of 2008. A privately held company, KPA focuses its efforts on the acquisition, development, licensing and marketing of pharmaceutical products. Its lead product, LIPOFEN(R) (fenofibrate capsules), is indicated as adjunctive therapy to diet to reduce elevated TG and to increase HDL-C in adult patients with primary hypercholesterolemia or mixed dyslipidemia.

Kowa Research Institute, Inc. (KRI), a division of KCL located in the Research Triangle Park area of North Carolina, is responsible for the clinical development of drug candidates in the United States for KCL. KRI was established in California in 1997 and began operations at its current location in 2003.

For more information about Kowa, please visit www.kowapharma.com.

References

(1) Cziraky MJ et al Am J Cardiol 2006;97:61C-68C

SOURCE Kowa Company Ltd., Kowa Pharmaceuticals America, Inc., and Kowa Research Institute, Inc.


Source: newswire



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