Pitavastatin is non-inferior to atorvastatin and simvastatin and demonstrates sustained efficacy and tolerability over 52 weeks

Pitavastatin represents long-term treatment option for patients with primary hypercholesterolaemia or combined dyslipidaemia

Milan, 21 September 2009 – New phase III data presented at the European Society of Cardiology congress (ESC) demonstrated that pitavastatin is non-inferior to atorvastatin and simvastatin at usual therapeutic doses in patients with primary hypercholesterolemia or combined dyslipidemia, as measured by reduction of low density lipoprotein cholesterol (LDL-C) from baseline. 

LDL-C target attainment data was similar when comparing pitavastatin to first-line drugs atorvastatin and simvastatin, although pitavastatin demonstrated significantly higher LDL-C target attainment compared to simvastatin in the lower dose study-arm (pitavastatin 2 mg vs simvastatin 20 mg) (p=0.047).  Furthermore, continued gradual increases in high density lipoprotein cholesterol (HDL-C) were observed over the long-term, supported by data from a 52 week extension study. Pitavastatin also demonstrated a favourable safety and tolerability profile to 52 weeks, the latter exemplified by a low rate of discontinuations due to adverse events, which were comparable to those with simvastatin or atorvastatin.

“This study confirms that pitavastatin is an effective and well tolerated long-term treatment option for patients with hypercholesterolemia or combined dyslipidemia,” commented Dr. Leiv Ose, MD PhD, Rikshospitalet, Oslo University Hospital, Norway, and Study Investigator. “Many patients do not reach LDL-C targets with current therapies due to a number of factors, especially non-compliance, and a statin which has the potential to improve long-term treatment compliance is welcomed.”

The primary objective of the two phase III, double blind, active-controlled studies was to demonstrate non-inferiority of pitavastatin to atorvastatin and simvastatin, as measured by the reduction of LDL-C. After a 6-8 week wash-out period, patients with primary hypercholesterolemia or combined dyslipidemia who had an average LDL-C >4.2 mmol/L (160 mg/dL) and >5.7 mmol/L (220 mg/dL) and a triglycerides (TG) level of >4.6 mmol/L (400 mg/dL) were treated for 12-week duration as follows:

• Study 1: 830 patients (46% males; mean 58 years) were randomised to one of four treatment groups, pitavastatin 2 mg, pitavastatin 4 mg, atorvastatin 10 mg or atorvastatin 20 mg (all doses QD) using up-titration for higher doses.
• Study 2: 857 patients (39% males; mean 58 years) were randomised to one of four treatment groups, pitavastatin 2 mg, pitavastatin 4 mg, simvastatin 20 mg or simvastatin 40 mg (all doses QD) using up-titration for higher doses.

Secondary objectives were to assess National Cholesterol Education Program (NCEP) and European Atherosclerosis Society (EAS) LDL-C target attainment, other lipid and lipoprotein fractions, safety and tolerability. 

1355 patients (42.5% males; mean age 58.6 years) who completed the two initial studies took part in an open-label extension to assess the long-term safety and tolerability of pitavastatin 4 mg (QD) for up to 52 weeks. Secondary objectives were to assess NCEP and EAS LDL-C target attainment, other lipid and lipoprotein fractions.

Pitavastatin was well tolerated to 52 weeks; no serious treatment-emergent adverse event (TEAE) was related to pitavastatin, with the most commonly reported TEAEs being increased blood creatinine kinase (5.8%), nasopharyngitis (5.4%) and myalgia (4.1%). Additionally, there were no clinically significant abnormalities in routine laboratory variables, urinalysis, vital signs or 12-lead ECG. Continued gradual increases in HDL-C were observed over 52 weeks and reductions in LDL-C were sustained over 52 weeks thus demonstrating sustained efficacy of pitavastatin over the long-term.

“Data from these pivotal, phase III studies show that pitavastatin has a robust efficacy, safety and tolerability profile, and in terms of LDL-C reduction, stands up to atorvastatin and simvastatin at usual therapeutic doses,” said Dr Neil Hounslow, Vice President of scientific affairs, Kowa Research Europe. “With sustained efficacy, low rates of discontinuations due to adverse events and continued increases in HDL-C observed over 52 weeks, pitavastatin shows great promise for the long-term treatment of patients with hypercholesterolemia or combined dyslipidemia.”

Notes to editors

Methodology:
• In the two 12-week studies, pitavastatin was considered non-inferior if the lower bound on the 95% confidence limit for the percent change in low density lipoprotein cholesterol (LDL-C) from baseline was >-6%, for all doses.

Results:
• Pitavastatin (PIT) was non-inferior to atorvastatin (ATO) in terms of the reduction in LDL-C (PIT 2 mg -37.9%; ATO 10 mg -37.8%: PIT 4 mg -44.6%; ATO 20 mg -43.5%).
• The LDL-C reduction was greater with pitavastatin 2 mg than simvastatin 20 mg (PIT 2 mg -38.99%; SIM 20 mg -34.97%). PIT 4 mg was non-inferior to SIM 40 mg in terms of the LDL-C reduction (PIT 4mg -43.97%; SIM 40mg -42.84%)
• The proportion of patients that met the EAS LDL-C target was significantly greater with pitavastatin
2 mg; 62.9% compared with simvastatin 20 mg; 52.1% (p=0.047). Total cholesterol (TC), and non-HDL-C showed significant decreases with pitavastatin 2 mg compared with simvastatin 20 mg (p=<0.05).
• Continued gradual increases in HDL-C were observed over 52 weeks (57.0 mg/dL at week 52 compared with 52.9 mg/dL at the end of the double-blind phase). Non-HDL-C, hs-CRP and oxidised LDL showed a sustained decrease at week 52.
• The number of patients who achieved NCEP and EAS LDL-C at 52 weeks was 74.0% and 73.5% respectively, up from 71.5% and 69.4% at the end of the double-blind phase. Similarly, reductions in LDL-C were sustained over 52 weeks (104.3 mg/dL at week 52 compared with 105.6 mg/dL at the end of the double-blind phase).

Lipid and lipoprotein fractions assessed:
Total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), non-HDL-C, TC:HDL-C ratio, non HDL-C:HDL-C ratio, triglycerides (TG), apolipoprotein B (Apo-B) and apolipoprotein A1 (Apo-A1), Apo-B:Apo-A1 ratio, high sensitivity C-reactive protein (hs-CRP), oxidised LDL.

About pitavastatin
Pitavastatin (a statin) is a fully synthetic and highly potent inhibitor of HMG-CoA reductase used for primary hypercholesterolaemia and combined dyslipidaemia. Pitavastatin has a unique cyclopropyl group on the base structure common to the statin class.  Since its 2003 launch in Japan, pitavastatin has accumulated millions of patient-years of exposure. Many of these patients have comorbidities and are taking multiple medications. Kowa received FDA approval of pitavastatin  for the primary treatment of hypercholesterolemia and combined dyslipidemia in August 2009, and is expected to launch in the U.S. during Q1 of 2010. Additionally, Kowa filed in Europe in August 2008 using the decentralised authorisation procedure. In Europe, pitavastatin will be marketed by Recordati. Pitavastatin will be available in three dosage strengths (1, 2 and 4 mg).

About Recordati
Recordati, established in 1926, is a European pharmaceutical group, listed on the Italian Stock Exchange (Reuters RECI.MI, Bloomberg REC IM, ISIN IT 0003828271),with a total staff of over 2,950, dedicated to the research, development, manufacturing and marketing of pharmaceuticals. It has headquarters in Milan, Italy, operations in the main European countries, and a growing presence in the new markets of Central and Eastern Europe.  A European field force of over 1,450 medical representatives promotes a wide range of innovative pharmaceuticals, both proprietary and under license, in a number of therapeutic areas including a specialized business dedicated to treatments for rare diseases. Recordati’s current and growing coverage of the European pharmaceutical market makes it a partner of choice for new product licenses from companies which do not have European marketing organizations.  Recordati is committed to the research and development of new drug entities within the cardiovascular and urogenital therapeutic areas and of treatments for rare diseases.  Consolidated revenue for 2008 was € 689.6 million, operating income was € 144.7 million and net income was € 100.4 million.

For further information:

Recordati website: www.recordati.com

About Kowa
Since its establishment in 1894, Kowa has grown into a multinational Japanese company actively engaged in various manufacturing and trading activities in the fields of pharmaceutical, life science and information technology, textiles, machinery and various consumer products. Kowa focuses its efforts on the acquisition, development, licensing and marketing of pharmaceutical products. During its long history, Kowa has consistently strived to meet the changing needs of the global market, and with its continuing entrepreneurial initiative, is determined to meet the needs of future generations. It is this commitment to consistency and initiative in an ever-changing world that Kowa vows to carry forward through each generation.

For more information about Kowa, please visit www.kowa.com.
CONTACT:
Laura Anderson
+44 (0)207 861 3033
l.anderson@bellpottingerhealth.com

Statements contained in this release, other than historical facts, are "forward-looking statements" (as such term is defined in the Private Securities Litigation Reform Act of 1995). These statements are based on currently available information, on current best estimates, and on assumptions believed to be reasonable. This information, these estimates and assumptions may prove to be incomplete or erroneous, and involve numerous risks and uncertainties, beyond the Company’s control. Hence, actual results may differ materially from those expressed or implied by such forward-looking statements. All mentions and descriptions of Recordati products are intended solely as information on the general nature of the company’s activities and are not intended to indicate the advisability of administering any product in any particular instance.