BASEL, Switzerland and BRIDGEWATER, N.J., Dec. 19, 2006 (PRIME NEWSWIRE) — Speedel (SWX:SPPN) announced today that in the interests of patient safety it has stopped the current pivotal Phase III clinical trial of SPP301 (Avosentan) in diabetic nephropathy (diabetic kidney disease). This decision was taken by the ASCEND(1) trial’s Steering Committee based on a recommendation from the Data Safety Monitoring Board to stop the trial, following a significant imbalance in fluid retention in patients amongst the study arms. The company is informing health authorities including the U.S. Food and Drug Administration and is in the process of notifying all clinical investigators in the trial. The company also said that the compound will be evaluated for potential new clinical trials in diabetic kidney disease and other indications, and that an announcement concerning the next steps for SPP301 should occur around the middle of 2007.
Giancarlo Viberti, Chairman of the ASCEND Steering Committee, Professor of diabetes and metabolic medicine at Guy’s Hospital London, stated: “We are highly committed to carrying out a thorough analysis of the data from the ASCEND trial to devise the best possible way to continue development of SPP301. There is a need to generate an optimum study design for potential new clinical trials with this compound. Diabetic kidney disease is a large and growing unmet medical need which requires innovative therapies to which SPP301 could make a significant contribution.”
Dr. Jessica Mann, Medical Director of Speedel, commented: “This decision to stop the current Phase III trial is based on data showing that patients taking SPP301 developed higher levels of fluid retention than those on placebo. Fluid retention is not unusual in patients who have severe diabetic kidney disease. However, given the fragility of these patients, the company is being prudent in not continuing to expose them to any further complications in this study.”
Dr. Alice Huxley, CEO, said: “We are disappointed that this promising therapy could not complete the current Phase III trial for diabetic kidney disease. We remain hopeful about the potential therapeutic benefits of SPP301 and we will now use the next 6 months to evaluate the study data and explore possible alternative trial designs for SPP301 in diabetic kidney disease and its potential in other indications. This is a setback to our SPP301 development programme, and it demonstrates the potential risks linked to the pharmaceutical industry’s pursuit of innovation.”
SPP301, a once-a-day oral endothelin-A receptor antagonist (ERA) showed in Phase II trials that it decreases urinary albumin excretion rate (UAER) and total cholesterol in patients with diabetic kidney disease when administered on top of standard treatment. Diabetic nephropathy (DN) represents a large and growing unmet medical need with a high mortality rate affecting an estimated 7.9 million people(2) diagnosed with diabetes in the U.S., Europe and Japan. Speedel has exclusive worldwide development and commercialisation rights to SPP301 under a licensing agreement with Roche.
Web Cast and Conference Call
At 15.00 CET /14:00 London/ 09:00 EST today December 19, 2006, the company will host a web cast which can be accessed at http://www.speedel.com/section/6/subsections/7. In addition participants may join a teleconference facility using the following telephone numbers:
Switzerland: +41 (0) 44 580 34 09 UK: +44 (0) 845 2450 248 USA: +1 866 224 3295 Passcode for all: 4463058
Slides for the web cast will be downloadable and the web cast will be accessible on the company’s website until January 14, 2007.
Full Year 2006 Results March 23 Annual Report Published April 12 Q1 Results May 04 AGM May 10 Q2 Results August 15 Q3 Results November 14
Phase III pivotal trial — ASCEND(3)
The Phase III pivotal morbidity and mortality ASCEND trial, which began in July 2005, was a randomized, placebo-controlled study with over 2000 patients, designed to assess time to doubling of serum creatinine, end stage renal disease or death in type II diabetic patients with nephropathy. It investigated the effects of therapy with SPP301 (25 mg or 50 mg) or placebo, administered once daily on top of standard treatment which consists of angiotensin converting enzyme inhibitors (ACE-Is) or angiotensin receptor blockers (ARBs).The study, which had been discussed and agreed with the FDA and the EMEA, was conducted in Europe, Americas and Asia and was expected to be completed by 2009 but was stopped in December 2006. The FDA has granted Fast Track status for SPP301 in this indication and had agreed a Special Protocol Assessment defining the design and endpoints for this Phase III trial.
Phase IIb results demonstrate strong efficacy and good safety
Results of the Phase IIb trial were presented in November 2005 at the American Society of Nephrology(4). A total of 286 patients were enrolled in this randomized, placebo-controlled, double-blind, parallel design trial. It investigated the effects on UAER of 12-week therapy with SPP301 (5 mg, 10 mg, 25 mg or 50 mg) or placebo, administered once daily on top of standard treatment (consisting of angiotensin converting enzyme (ACE) inhibitors or angiotensin receptor blockers (ARBs). Compared to placebo, all doses of SPP301 decreased UAER significantly (p less than 0.001), with the highest two doses (25 mg, 50 mg) demonstrating the greatest reduction in UAER. There was also a significant reduction in total cholesterol at all doses (p less than 0.001) compared to placebo.
SPP301 was shown to reduce proteinuria by at least 30% on top of standard treatment for 55% of all patients across all dose groups. This is a remarkable additive effect in patients already receiving ACE-Is or ARBs, since these drugs are known to have strong antiproteinuric-effects on their own. Importantly, data from the U.S. National Kidney Foundation(5) suggests that such a significant reduction in proteinuria by SPP301 could impact morbidity and mortality in patients with diabetic kidney disease.
In this Phase II trial SPP301 also had a good safety profile and whereas other ERAs have previously been associated with liver toxicity, SPP301 has not been associated with this side effect so far. In this Phase IIb trial, no significant increases in liver enzymes, aspartate aminotransferase (ASAT) or alanine aminotransferase (ALAT) were observed with SPP301 compared to placebo.
SPP301 is a once daily oral endothelin-A receptor antagonist that Speedel licensed from Roche in October 2000. SPP301, a second generation ERA, was developed out of Roche’s endothelin research and drug discovery program, and was specifically optimised for improved liver safety. Speedel took the compound through a number of Phase I and exploratory Phase IIa clinical trials before selecting the novel indication of diabetic nephropathy for a Phase IIb clinical trial, the headline results for which were announced in March 2005. The Phase III ASCEND study began in July 2005 and was stopped in December 2006. Speedel has exclusive worldwide development and commercialisation rights under the licensing agreement with Roche.
About Diabetic Nephropathy
Definition: Diabetic nephropathy refers to any deleterious effect on kidney structure and/or function caused by diabetes mellitus. More specifically, diabetic nephropathy is thought of in stages, the first being that characterized by microalbuminuria (30-300 mg urinary albumin per 24 hours). This may progress to overt nephropathy or macroalbuminuria (greater than 300 mg urinary albumin per 24 hours). Later still, progressive renal functional decline is characterized by significant decreases in glomerular filtration rate accompanied by rises in serum creatinine, the final result of which is End Stage Renal Disease.
Current therapies include — amongst others — drugs that work on the renin-angiotensin system such as ACE inhibitors and ARBs, which have an antihypertensive effect as well as a renoprotective effect and have been shown to slow disease progression. However, 20-40% of patients with markers of early disease still progress to advanced kidney damage and eventually End Stage Renal Disease and death(6). Diabetic Nephropathy is a new indication for endothelin receptor antagonists, and the positive Phase II results for SPP301 indicate considerable additional benefit on top of current therapies taken by patients suffering from this chronic disease
Prevalence: According to the WHO in 2000, some 177 million people around the world had some form of diabetes, including undiagnosed cases. About 20-40% of patients with type 1 or type 2-diabetes develop nephropathy.(7) Current treatments (primarily antihypertensive treatment and inhibition of the renin angiotensin system) slow progression of DN, but it remains an unmet medical need, with a high mortality rate.
About Endothelin Receptor Antagonists
Pharmacological blockade of the endothelin system constitutes a relatively new concept for modulating haemodynamic and cellular functions. Substantial evidence from animal testing and clinical studies suggest that endothelin plays a pivotal role in several diseases such as hypertension, chronic heart failure, and chronic nephropathies. Endothelin triggers renal vasoconstriction, decreases glomerular filtration rate and modulates sodium excretion and water balance at the level of the proximal tubule and medullary collecting ducts, by mechanisms that are still unclear. Endothelin also stimulates the renin angiotensin system and atrial natriuretic peptide release and inhibits vasopressin-mediated water re-absorption in the collecting duct. In preclinical testing, chronic administration of Endothelin Receptor Antagonists protected animals, including those with induced diabetes, from developing renal injury.
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(8)), the first-in-class renin inhibitor, is partnered with Novartis Pharma for development and commercialisation in hypertension; SPP100 was filed with the FDA in the U.S. in Q1 2006 and with the EMEA in the EU in Q3 2006. Our pipeline covers three different modes of action, and in addition to SPP100, includes SPP301 in Phase III (on hold), SPP200 in Phase II, SPP635 in Phase Il, 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 March 2006 the company raised gross proceeds of CHF 83.95 million (approximately EUR 53m or US$64m) through the public offering of 500,000 treasury shares. Previously, as a private company, we raised gross proceeds of CHF 239 million (approximately EUR 154 million or US$183 million) from private placements of equity securities and two convertible loans and we have had total revenues, principally from milestone payments, of CHF 57.7 million (approximately EUR 37 million or US$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.
(1) Avosentan on doubling of Serum Creatinine, ENd stage renal disease and death in Diabetic nephropathy (2) Decision Resources, October 2004 (3) Avosentan on doubling of Serum Creatinine, ENd stage renal disease and death in Diabetic nephropathy (4) The ETA -- selective antagonist SPP301 on top of standard treatment reduces urinary albumin excretion rate in patients with diabetic nephropathy. Presented at 38th Annual Meeting of the American Society of Nephrology, November 11, 2005, Philadelphia. Rene Wenzel, Jessica Mann, Christiane Jurgens, Ilknur Yildirim, Heike Bruck, Thomas Philipp, Anna Mitchell. (5) Keane WF, Eknoyan G. Proteinuria, albuminuria, risk, assessment, detection, elimination (PARADE): a position paper of the National Kidney Foundation. Am J Kidney Dis. 1999 May; 33 (5): 1004-10 (6) Diabetes Care, American Diabetes Association 2004 (7) Diabetes Care, American Diabetes Association 2004 (8) Tekturna (SPP100, aliskiren) is a registered trade name of Novartis Pharma
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CONTACT: Speedel Nick Miles, Director Communications & Investor Relations +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 [email protected] www.speedel.com Hirschgasslein 11 CH - 4051 Basel Switzerland Speedel Pharmaceuticals Inc. Frank LaSaracina, Managing Director +1 732 537 2290 F +1 732 537 2292 M +1 908 338 0501 [email protected]del.com www.speedel.com 1661 Route 22 West P.O. Box 6532 Bridgewater, NJ 08807 United States of America