Basel/Switzerland and Bridgewater NJ/USA, 17 June 2008 -- Speedel Holding Ltd. (Swiss:SPPN.SW - News) highlighted today that Novartis is to expand the clinical trial programme with SPP100 (aliskiren; Rasilez/Tekturna[1]) to study organ protection potential beyond the already shown powerful reduction of blood pressure. Novartis announced details of two new long-term outcome studies in its landmark ASPIRE HIGHER clinical trial programme. This series of trials now form the largest and most far-reaching cardio-renal outcomes programme worldwide.
The two new studies are to evaluate the organ protection potential of the first-in-class direct renin inhibitor SPP100 (aliskiren; Rasilez/Tekturna[1]) for the treatment of heart failure and prevention of cardiovascular disease in the elderly, a patient segment that is predicted to more than double between 2000 and 2030[2]. A third trial already under way is studying cardio-renal outcomes in diabetes.
Approximately one billion people worldwide today are affected by high blood pressure. This figure is estimated to further increase in the future[3]. The medical need for adequate treatments is obvious, as high blood pressure is a sign that many organs in the body could be under threat[4]. SPP100 (aliskiren; Rasilez/Tekturna[1]) works by directly inhibiting renin, an enzyme that triggers a process leading to high blood pressure and organ damage. By inhibiting renin at the point of activation, SPP100 (aliskiren; Rasilez/Tekturna[1]) effectively reduces blood pressure and may also lead to greater protection against complications such as organ damage[5],[6].
Dr. J. Chris Jensen, Head of Scientific Affairs comments: " We are excited to see that Novartis is investigating the benefits of renin inhibition on top of effective blood pressure reduction in a wide variety of patient populations and clinical conditions. We expect the results of this outstanding landmark programme with SPP100 (aliskiren; Rasilez/Tekturna[1]) to show the benefits of renin inhibition beyond blood pressure control in medical practice. Ultimately, we see a new gold standard in antihypertensive treatment - based upon organ-protective effects. Speedel’s next generation of renin inhibitors are specifically designed to improve these organ-protective effects, e.g. to aid kidney protection.”
The ASPIRE HIGHER programme
This clinical programme includes three major outcome studies:
* ALTITUDE will determine whether Rasilez/Tekturna[1], added to conventional therapy, delays heart and kidney complications in around 8,600 patients with type 2 diabetes at high risk for cardiovascular and renal events. The study began in late 2007 with completion anticipated by 2012.
* ATMOSPHERE will evaluate the effects of Rasilez/Tekturna[1] on cardiovascular morbidity and mortality in patients with acute and chronic congestive heart failure on top of standard therapy.
* APOLLO will assess the effectiveness of Rasilez/Tekturna[1] in preventing cardiovascular morbidity and mortality in elderly patients with or without high blood pressure and other risk factors.
In addition to these megatrials, the ASPIRE HIGHER programme includes a comprehensive range of short-to-medium term studies to assess the potential organ protection benefits of Rasilez/Tekturna[1] across a broad range of cardio-renal conditions including heart failure, post-acute coronary syndromes, post-myocardial infarction, left ventricular hypertrophy, coronary artery disease and diabetic nephropathy. Other studies are designed to further confirm the powerful blood pressure lowering effect of Rasilez/Tekturna[1].
The findings from three earlier studies in the ASPIRE HIGHER programme have already been reported. The AVOID study that has recently been published in the New England Journal of Medicine showed that treatment with SPP100 (aliskiren; Rasilez/Tekturna[1]) reduced albuminuria, a key indicator of kidney disease, in type 2 diabetic patients with kidney disease and high blood pressure[7]. The ALOFT study showed that treatment with SPP100 (aliskiren; Rasilez/Tekturna[1]) reduced BNP, a marker of heart failure severity[8]. In the ALLAY study, the combination of SPP100 (aliskiren; Rasilez/Tekturna[1]) and the angiotensin receptor blocker (ARB) losartan achieved a numerically greater reduction in left ventricular hypertrophy (LVH) than losartan alone, although the result was not statistically significant[9]. LVH is a marker of cardiac damage associated with an increased risk of cardiovascular events.
About SPP100 (aliskiren, Tekturna/Rasilez[1])
SPP100 (aliskiren, Tekturna/Rasilez[1]) is the first-in-class oral direct renin inhibitor. The development of SPP100 is the result of over 20 years of research on renin. Renin is the rate-limiting enzyme at the top of the Renin Angiotensin System (RAS), a process leading to high blood pressure and organ damage. The RAS is a cascade, starting with renin, leading to angiotensin I and finally to angiotensin II. Angiotensin-converting enzyme inhibitors (ACE-Is) and angiotensin II receptor antagonists (ARBs) have been developed to block this system “down stream” and have shown clinical efficacy in patients with hypertension and other cardiovascular diseases.
By inhibiting renin at the top of the RAS, SPP100 decreases the system’s activity, as measured by plasma renin activity (PRA). Lowering PRA is believed to be very important in end-organ protection (e.g. heart and kidney). PRA is an independent risk factor and direct surrogate marker for several cardio-renal diseases, such as myocardial infarction and chronic renal disease. Direct renin inhibitors lower PRA whereas most current leading anti-hypertensive drug classes such as ACE-Is and ARBs increase PRA levels.
Speedel in-licensed SPP100 from Novartis in 1999 and successfully completed 18 clinical trials, through Phase I and II in about 500 patients and healthy volunteers. Based on the results generated during this programme, Novartis exercised a license-back option in 2002, and subsequently Novartis started trials with SPP100 in Phase III as monotherapy for hypertension and in Phase IIb as combination therapy. Regulatory approval was given by the US FDA in March 2007 and by the EU in August 2007. A first fixed-dose combination of SPP100 and the diuretic HCT was approved in the US in January 2008.
Speedel believes that it is the first company to establish successfully a clinical proof of concept in Phase II and to have developed and filed for patent protection a commercially viable manufacturing process for a renin inhibitor, an area of industry research for over 20 years. In a Phase II study of 200 patients conducted by Speedel, it was demonstrated that SPP100 achieves dose-dependent blood pressure reduction. The study also showed that 150mg and 300mg SPP100 once daily were comparable to Losartan 100mg, which is double the usual starting dose of this ARB[10].
About Speedel
Speedel is a public biopharmaceutical company that seeks to create value for patients, partners and investors by developing innovative therapies for cardiovascular and metabolic diseases. Speedel is a world leader in renin inhibition, a promising new approach with significant potential for treating cardiovascular diseases. Our lead compound SPP100, Aliskiren (Tekturna/Rasilez[1])the first-in-class direct renin inhibitor, was in-licensed from Novartis in 1999 and licensed-back to Novartis Pharma in 2002 for further development and commercialisation; SPP100 was approved by the FDA in the US in March 2007, and by the EMEA in the EU in August 2007. Our pipeline covers four different modes of action, and in addition to SPP100, includes SPP301 (an endothelin receptor A antagonist) in Phase II, SPP200 (a direct thrombin inhibitor) in Phase II, the next generation renin inhibitors SPP635 (in Phase Il), SPP1148 and SPP676 (both in Phase I) and several pre-clinical projects, including SPP2475 (aldosterone synthase inhibitor).
Speedel develops novel product candidates through focused innovation and smart drug development from lead identification to the end of Phase II. We either partner with big pharma for Phase III and commercialisation in primary-care indications, or we may ourselves complete Phase III development in specialist indications. Candidate compounds for development and the company’s intellectual property come from our late-stage research unit Speedel Experimenta and from in-licensing. Our team of approximately 80 employees, including over 30 experienced pharmaceutical scientists, is located at our headquarters and laboratories in Basel, Switzerland and at offices in New Jersey, USA and Tokyo, Japan.
Speedel was founded in 1998 as a private company. In September 2005 the company’s shares were listed on the SWX Swiss Exchange under the symbol SPPN. Further information is available at www.speedel.com.
Forward looking statements
This press release includes forward-looking statements that involve substantial risks and uncertainties. These forward-looking statements are based on our current expectations and projections about future events. All statements, other than statements of historical facts, regarding our strategy, future operations, future financial position, future revenues, projected costs, prospects, plans and objectives of management are forward-looking statements. The word “may” and similar expressions are intended to identify forward-looking statements, although not all forward-looking statements contain these identifying words. We may not actually achieve the plans, intentions or expectations described in these forward-looking statements and you should not place undue reliance on them. There can be no assurance that actual results of our research and development activities and our results of operations will not differ materially from these expectations. Factors that could cause actual results to differ from expectations include, among others: our or our partners’ ability to develop safe and efficacious products; our or our partners’ ability to achieve positive results in clinical trials; our or our partners’ ability to obtain marketing approval and market acceptance for our product candidates; our ability to enter into future collaboration and licensing agreements; the impact of competition and technological change; existing and future regulations affecting our business; changes in governmental oversight of pharmaceutical product development; the future scope of our patent coverage or that of third parties; the effects of any future litigation; general economic and business conditions, both internationally and within our industry, including exchange rate variations; and our future financing plans.
[1] Tekturna/Rasilez® are Novartis trademarks.
[2] Sigg R. A Global Overview of Social Security in the Age of Longevity. Available at: www.un.org/esa/population/meetings/EGMPopAge/ Paper 6. Accessed 12 June 2008.
[3] Kearney P et al. Global Burden of Hypertension: Analysis of Worldwide Data. Lancet 2005;365:217-23.
[4] International Society of Hypertension. Frequently Asked Questions on Hypertension and its Treatment. Available at: http://www.ish-world.com/default.aspx?FAQs. Accessed 4 June 2008.
[5] Müller D, Luft F. Direct Renin Inhibition with Aliskiren in Hypertension and Target Organ Damage. Clin J Am Soc of Nephrol. 1:22-228, 2006.
[6] Shafiq MM, Menon DV, Victor RG. Oral Direct Inhibition: Premise, Promise, and Potential Limitations of a New Antihypertensive Drug. Am J Med. 2008 Apr;121(4):265-71.
[7] Parving H-H et al. Aliskiren Combined with Losartan in Type 2 Diabetes and Nephropathy. N Eng J Med June 5, 2008; 358:2433-46.
[8] McMurray J, Pitt B, Latini R, et al. Effects of the Oral Direct Inhibitor Aliskiren in Patients with Symptomatic Heart Failure. Circulation: Heart Failure. 2008;1:17-24.
[9] Solomon S, Appelbaum E, Manning WJ, et al. Effect of the Direct Renin Inhibitor Aliskiren, Either Alone or in Combination With Losartan, Compared to Losartan, on Left Ventricular Mass in Patients With Hypertension and Left Ventricular Hypertrophy: The Aliskiren Left Ventricular Assessment of Hypertrophy (ALLAY) Trial. Late Breaker presentation at American College of Cardiology 57th Scientific Sessions 2008.
[10] Stanton A, Jensen C, Nussberger J, O’Brien E. Blood pressure lowering in essential hypertension with an oral renin inhibitor, aliskiren. Hypertension 2003; 42: 1137-1143.
For further information please contact:
Dr. Harald F. Schaefer Director Communications & Investor Relations Speedel Hirschgässlein 11 CH - 4051 Basel Switzerland
T +41 (0) 61 206 40 00 D +41 (0) 61 206 40 14 F +41 (0) 61 206 40 01 M +41 (0) 79 629 76 71 E harald.schaefer@speedel.com http://www.speedel.com
Frank LaSaracina Managing Director Speedel Pharmaceuticals Inc 1661 Route 22 West P.O. Box 6532 Bridgewater, NJ 08807 United States of America
T +1 732 537 2290 F +1 732 537 2292 M +1 908 338 0501 E frank.lasaracina@speedel.com http://www.speedel.com
Press Release (PDF): http://hugin.info/135077/R/1228457/260522.pdf
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Contact: Source: Speedel Holding AG
