SOURCE: Speedel Holding AG

November 05, 2007 01:07 ET

SPP100 (TEKTURNA/RASILEZ) DECREASES PROTEINURIA IN DIABETIC PATIENTS

- BENEFITS OF RENIN INHIBITORS ON TOP OF STANDARD THERAPY-

BASEL, SWITZERLAND and BRIDGEWATER, NJ--(Marketwire - November 5, 2007) - - BENEFITS OF RENIN INHIBITORS ON TOP OF STANDARD THERAPY-


Basel/Switzerland and Bridgewater NJ/USA, 5 November 2007

Speedel Holding Ltd (SWX: SPPN) today welcomes the promising results of SPP100 (Tekturna/Rasilez[1]) in the AVOID[2] Phase III clinical trial with diabetic patients which were presented on 4 November at the American Society of Nephrology Renal Week Congress in San Francisco, California by Professor Hans-Henrik Parving of the Department of Endocrinology, Righospitalet, Copenhagen, Denmark. The study was sponsored by Novartis and the results show that SPP100, the first-in-class direct renin inhibitor, further lowers proteinuria in diabetic patients, independent of blood pressure, when administered on top of losartan (ARB[3]), a standard therapy used to treat diabetic kidney disease.

SPP100 was approved by the US Food and Drug Administration (FDA) in the US in March 2007 under the trade name Tekturna and by the European Union under the trade name Rasilez in August 2007 to treat hypertension both as monotherapy and in combination with other anti-hypertensives. Novartis announced in July 2007 that it was also approved in Switzerland. Speedel successfully developed SPP100 through Phase I and II clinical trials before Novartis exercised its license-back option in 2002.

Dr. Alice Huxley, CEO, said: "We are encouraged by the potential of this novel class of therapy to provide patients with benefits over and beyond blood pressure lowering. High blood pressure is a co-morbidity found in 74% of diabetes patients[4] and it is clear that new therapies are required to treat this vulnerable patient population. These AVOID study results highlight the possible long-term benefits of using renin inhibitors. Our next generation compounds are specifically designed to further enhance the effects on proteinuria, as we have demonstrated in our preclinical research."

AVOID study results[5]

599 patients were enrolled in this multi-national, randomised, double blind Phase III study. There was a 3-months open-label run-in period with patients receiving losartan 100 mg once per day (OD) in addition to optimal antihypertensive therapy. After these 3 months, patients were randomised to receive 6-months treatment with placebo or aliskiren (150 mg OD for 3 months followed by forced titration to 300 mg OD for another 3 months) on top of losartan. The primary outcome was reduction in early morning urinary albumin creatinine ratio (UACR) from baseline to end of study. UACR is a widely accepted biomarker for measuring the health of a patient's kidneys, and reductions in albuminuria are associated with improved renal function and decreased risk of end stage renal disease.[6]

SPP100 (aliskiren) provided a significant 20% reduction in mean UACR on top of standard therapy compared with placebo after 24 weeks (p= 0.0009, 95% CI: 9-30) and aliskiren also significantly reduced mean urinary albumin excretion rate (UAER) by 21% compared to placebo (p=0.009; 95% CI: 5-30). The number of patients with 50% reduction in UACR at the end of the study was 24.7% for aliskiren treated patients versus 12.5% for placebo (p = 0.0002).

Estimated glomerular filtration rate (eGFR) was preserved by aliskiren during the study. Blood pressure was similar between the two treatment groups and remained controlled throughout the study; changes in albuminuria did not correlate to changes in blood pressure. The total number of adverse events and serious adverse events was similar in the two groups. Single-measurement serum-potassium 6.0mEq/L occurred in 4.7% vs. 1.7% (difference not significant) in the aliskiren and placebo groups respectively.

The AVOID study is the second of a series of trials in ASPIRE HIGHER, an extensive ongoing clinical programme by Novartis studying the 'beyond blood pressure' benefits of SPP100 due to direct renin inhibition. Data in patients with heart failure (ALOFT[7]) were presented earlier this year.

ALTITUDE[8] study commenced to determine long-term benefits of Aliskiren

SPP100 is not currently indicated for the treatment of diabetic kidney disease. Novartis is currently recruiting for the ALTITUDE Phase III clinical trial to investigate whether the addition of aliskiren to conventional therapy provides additional cardio and reno-protection in patients with type 2 diabetes. The study is event driven and will conclude when about 1628 patients meet the primary endpoint, which is estimated to take about 4 years.

Next generation renin inhibitors

With three new renin inhibitors in clinical development, Speedel continues to build its mature pipeline by leveraging its expertise and experience in renin inhibition. This novel mode of action has been validated by the 2007 approval of SPP100 (Tekturna/Rasilez) in the US, EU and Switzerland where it is marketed by Novartis in these markets. Both Speedel and Novartis recently won the Wall Street Journal Gold Award for Technology Innovation, which was given to the companies for their work in discovering and developing SPP100 as an innovative therapy for hypertension. Speedel is developing a family of next generation renin inhibitors, and now has three compounds in the clinic: SPP635 in Phase IIa, SPP676 in Phase I and SPP1148 in Phase I.

Growing global health risks of high blood pressure

The Lancet published an editorial on 17 August 2007 which stated that: "The risk of becoming hypertensive during lifetime exceeds a staggering 90% for a person in a developed country." The editorial also observed that: "The increasingly common combination and interaction of obesity, diabetes, hyperlipidaemia and high blood pressure, if left untreated for too long, leads to cardiovascular disease, stroke, renal failure, dementia, and ultimately death. Worldwide, the estimated number of adults with hypertension was 972 million in 2000; 639 million live in developing countries. By 2025, the total number is expected to increase to 1.56 billion."[9]

About SPP100 (aliskiren, Tekturna/Rasilez[10] )

SPP100 (aliskiren, Tekturna/Rasilez) 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), one of the key regulators of blood pressure. 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.

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 (Stanton, Jensen, Nussberger, O'Brien, Hypertension.2003; 42: 1137-1143).

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 (Tekturna/Rasilez[11] ), 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 three different modes of action, and in addition to SPP100, includes SPP301 in Phase II, SPP200 in Phase II, SPP635 in Phase Il, SPP1148 and SPP676 in Phase I and several pre-clinical projects. 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 70 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.

In January 2007 the company raised gross proceeds of CHF 55.5 million (approximately EUR 34.3 million or USD 44.5 million) through a convertible bond issue. In March 2006 the company raised gross proceeds of CHF 83.95 million (approximately EUR 53m or USD 64m) through the public offering of 500,000 treasury shares. Previously, as a private company, we raised gross proceeds of CHF 255 million (approximately EUR 157 million or USD 204 million) from private placements of equity securities and two convertible loans including the conversion premiums. We have had total revenues, principally from milestone payments, of CHF 57.7 million (approximately EUR 37 million or USD 44 million). The company's shares were listed in September 2005 on the SWX Swiss Exchange under the symbol SPPN.


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.


- Ends -

[1] Tekturna/Rasilez® are Novartis trademarks
[2] Aliskiren in the Evaluation of PrOteinuria In Diabetes
[3] Angiotensin II receptor antagonists
[4] Selby JV et al. Am J Manage Care 2004: 10:163-70
[5] Parving H-H et al. AVOID Aliskiren in the Evaluation of
Proteinuria in Diabetes. Oral presentation at American Society of
Nephrology Renal Week Congress in San Francisco, California, November
2007. Poster SA-P01051
[6] GISEN group, Lancet 1997: 349:1857-63; de Zeeuw et al, Kidney Int
Suppl 2004: (92) S2-S6
[7] McMurray J et al. ALOFT - a 12 week safety evaluation of
aliskiren 150 mg vs. placebo when added to standard therapy for
stable heart failure. Oral presentation in Hotline I session at
European Society of Cardiology Congress 2007
[8] ALiskiren Trial In Type 2 diabetes Using cardio-renal Disease
Endpoints
[9] The Lancet:  2007; 370:539
[10] Tekturna/Rasilez® are Novartis trademarks
[11] Tekturna/Rasilez® are Novartis trademarks

For further information please contact


Nick Miles
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) 79 446 25 21
E nick.miles@speedel.com
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
www.speedel.com




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