WOKINGHAM, England, June 12, 2012 /PRNewswire/ --

Two papers published in the European Journal of Preventive Cardiology ^(1,2) complete the publication of data from the pitavastatin development programme by Japanese-headquartered company, Kowa.

Kowa now has clinical study data from nearly 25,000 patients for its novel and potent statin, pitavastatin, showing its efficacy and pharmacokinetics are consistent across the world.  The last tranche of primary data show pitavastatin is as effective as other commonly used statins at lowering low density lipoprotein cholesterol (LDL-C), with excellent tolerability. ^(3,4,5,6,7)

Pitavastatin is also effective at elevating high density lipoprotein (HDL-C) levels, reducing triglyceride (TG) levels, ^(8,5) and appears to have less effect on glycaemic control, ⁽³⁾ than some other statins.

Comparisons to simvastatin in patients with dyslipidemia at high risk of coronary heart disease showed the two statins to be equivalent. In one study, 355 patients were randomised between pitavastatin and simvastatin: both drugs were equally effective at reducing LDL-C but pitavastatin increased HDL-C by 6.8%, compared to 4.5% in the simvastatin arm, and was better than simvastatin at reducing triglycerides (TG). ⁽⁵⁾ This may make pitavastatin a good choice for the management of dyslipidemic patients at high cardiovascular risk.

An extension of this study over 44 weeks showed that pitavastatin's effects were sustained and while both treatments were generally well tolerated, fewer pitavastatin patients stopped treatment because of adverse events, although this was not statistically significant. ⁽⁴⁾

Another head to head comparison, in 857 patients with either primary hypercholesterolaemia or combined dyslipidemia, showed that pitavastatin was superior to simvastatin in terms of percentage reduction of LDL-C, at lower doses (pitavastatin 2 mg/day v. simvastatin 20 mg/day) and proved to be equivalent to simvastatin in percentage reduction of LDL-C at higher-doses (pitavastatin 4 mg/day v. simvastatin 40 mg/day). ⁽⁶⁾

Comparisons to atorvastatin showed reductions in LDL-C were not significantly different between the two treatments and attainment of National Cholesterol Education Program (NCEP) and European Atherosclerosis Society targets for LDL-C was similarly high for both treatment groups.^(3,7) Both treatments were well tolerated, including in patients with diabetes, but atorvastatin increased fasting blood glucose in patients with diabetes from baseline (+7.2%; p<0.05), whereas pitavastatin had no significant effect (+2.1%). The difference between treatments was significant (p=0.005).⁽³⁾

A comparison of the full range of doses of pitavastatin (1, 2, 4 mg) against the lowest doses of the best tolerated statin, pravastatin (10, 20, 40 mg) in elderly patients showed pitavastatin was as well tolerated as pravastatin.  Differing clinical outcomes were observed: pitavastatin was statistically, significantly better than pravastatin for all comparisons in total cholesterol and Apo-B reduction, in the medium- and high-dose group for HDL-C elevation, and in the low- and high-dose groups for TG reduction. ⁽¹⁾

This study was extended for 60 weeks to assess the safety and tolerability of pitavastatin 2 mg once daily or 4 mg if required. The majority of patients attained NCEP treatment targets on the 2 mg dose and only 17% required up titration to 4 mg daily.⁽²⁾ Only 15.6% subjects discontinued treatment during this time, but only half of them because of adverse events.⁽²⁾ There were no cases of severe myalgia, myopathy, myositis or rhabdomyolysis, and no significant findings on urinalysis, vital signs or 12-lead ECG.⁽²⁾

Other safety and tolerability studies of pitavastatin at its highest dose, 4 mg, show that efficacious LDL-C lowering is not associated with treatment- limiting side effects.⁽⁸⁾ In a study of 1,353 patients the reduction in LDL-C levels seen during double-blind studies was sustained, while HDL-C levels rose continually during follow up, ultimately increasing by 14.3% over the initial baseline at 52 weeks. ⁽⁸⁾ Changes in other lipid parameters (TG, total cholesterol, non-HDL-C, Apo-A1 and Apo-B, high sensitivity C-reactive protein, oxidised LDL) and ratios (total cholesterol: HDL-C, non-HDL-C:HDL-C and Apo-B:Apo-A1) were sustained during 52-weeks treatment.⁽⁸⁾

Pitavastatin was well tolerated: only 4.1% of patients withdrew from the study because of side effects and none of the serious adverse events were considered treatment-related.⁽⁸⁾

About LIVAZO

LIVAZO (pitavastatin) is a HMG-CoA reductase inhibitor indicated for patients with primary hyperlipidemia and mixed dyslipidemia as an adjunctive therapy to diet to reduce elevated TC, LDL-C, Apo B, TG, and to increase HDL-C. LIVAZO is predominantly metabolized via glucuronidation and is only minimally metabolized by CYP system, which may help reduce its potential for CYP-mediated drug-drug interactions.

LIVAZO, also known as LIVALO and ALIPZA in some markets, has been available in Japan  since 2003 and is available in South Korea, Thailand, China, Taiwan, the US, Portugal, Spain, Lebanon, Mexico, and Indonesia . It is approved in Australia and an application for licence has been filed in Central and South America.

About Kowa

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 was founded in 1947, and is focused on cardiovascular therapeutics, with sales of the company's flagship product,  pitavastatin (known as LIVALO, LIVAZO and ALIPZA in different markets)  totalling $520 million (14.3% market share) in Japan during 2010 and expected to exceed $700 million in the near future.

Kowa Research Europe Ltd. (KRE), established in 1999 in the United Kingdom, is responsible for European clinical trials for Kowa's strategic global pharmaceutical development.

Kowa Pharmaceutical Europe (KPE) Co. Ltd, established in 2000, is a specialty pharmaceutical company located in Wokingham, UK, focused primarily on cardiometabolic therapeutics. Working in harmony with KRE, these European pharmaceutical divisions of Japanese Kowa Company, Ltd. are committed to ground-breaking research, development and marketing to ensure quality products are made available to people around the world, enabling them to enjoy a better standard of health and a more comfortable life.

Visit our New Website: http://www.Kowapharmaceuticals.eu/

References

(1) Stender S, Budinski D, Hounslow N. Pitavastatin shows greater lipid lowering efficacy over 12 weeks than pravastatin in elderly patients with primary hypercholesterolemia or combined dyslipidaemia.  Eur J Prev Cardiol.

2012 Jun 8. [Epub ahead of print].

(2) Stender S, Budinski D, Hounslow N. Pitavastatin demonstrates long-term efficacy, safety and tolerability in elderly patients with primary hypercholesterolaemia or combined (mixed) dyslipidaemia. Eur J Prev Cardiol. 2012 Jan 23. [Epub ahead of print].

(3) Gumprecht J, Gosho M, Budinski D, Hounslow N. Comparative long-term efficacy and tolerability of pitavastatin 4 mg and atorvastatin 20-40 mg in patients with type 2 diabetes mellitus and combined (mixed) dyslipidaemia. Diabetes Obes Metab. 2011;13:1047-55.

(4) Eriksson M, Budinski D, Hounslow N. Long-term efficacy of pitavastatin versus simvastatin. Adv Ther. 2011;28:799-810.

(5) Eriksson M, Budinski D, Hounslow N. Comparative efficacy of pitavastatin and simvastatin in high-risk patients: a randomized controlled trial. Adv Ther. 2011;28:811-23.

(6) Ose L, Budinski D, Hounslow N, Arneson V. Comparison of pitavastatin with simvastatin in primary hypercholesterolaemia or combined dyslipidaemia. Curr Med Res Opin. 2009;25:2755-64.

(7) Budinski D, Arneson A, Hounslow N, Gratsiansky N. Pitavastatin compared with atorvastatin in primary hypercholesterolemia or combined dyslipidemia. Clinical Lipidology. 2009;3:291-302.

(8) Ose L, Budinski D, Hounslow N, Arneson V. Long-term treatment with pitavastatin is effective and well tolerated by patients with primary hypercholesterolemia or combined dyslipidemia. Atherosclerosis. 2010;210:202-8.

SOURCE Kowa Company, Ltd.