Speedel Starts Phase III Study of SPP301 in Diabetic Nephropathy

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Speedel pipeline now contains two potential blockbuster drugs in Phase III.

Speedel announced today the start of its Phase III study for SPP301, its once-a-day oral endothelin A receptor antagonist (ERA) in the indication of diabetic nephropathy (diabetic kidney disease). The ASCEND(1) study has begun with the first patient visit as per the schedule outlined by Speedel in March 2005 when the company reported successful completion of the Phase II clinical trials.

Dr. Alice Huxley, CEO of Speedel, commented: “This milestone is of major strategic importance for Speedel as SPP301 is the first drug which we have progressed into Phase III ourselves and it is a considerable commercial opportunity. Our mature and diverse pipeline now includes two Phase III products with blockbuster potential for major indications – SPP100 partnered with Novartis for hypertension and SPP301 for diabetic kidney disease. Both products have the potential to be first-in-class in their respective indications, and demonstrate Speedel’s commitment to innovative therapies for the large and growing markets of cardiovascular and metabolic diseases.”

Dr. Jessica Mann, Medical Director of Speedel, added: “The prevalence of diabetic nephropathy has been increasing dramatically in line with the rising numbers of diabetes patients worldwide. Diabetic nephropathy has a high mortality rate affecting an estimated 8.0 million people(2) diagnosed with diabetes in the US, Japan, and major European countries. Therapeutic options are limited at present. We believe SPP301 to have considerable potential as a breakthrough therapy with significant medical benefits for the people who suffer from this chronic disease.”

The Phase III pivotal ASCEND study is a randomized, placebo-controlled morbidity and mortality study with over 2,000 patients, designed to assess time to doubling of serum creatinine, end-stage renal disease or death in type 2 diabetes patients with overt diabetic nephropathy(3). Patients will be given either 25mg or 50mg of SPP301 once per day on top of standard therapy, or will receive standard therapy alone (i.e. the placebo arm). The study, which has been discussed and agreed with the FDA and the EMEA, will be conducted in about 260 clinical sites in Europe, USA and other countries. This is an event-driven study, and the current best estimate is that it will take approximately 3.5 years for enough events to occur in the composite end-point to demonstrate statistically significant efficacy. In view of the high unmet medical need diabetic nephropathy represents, SPP301 has been granted Fast Track Designation(4) and has undergone a Special Protocol Assessment by the FDA(5). This means that the review process is expedited and that assuming successful registration, SPP301 could be launched in the USA in late 2009 and in other countries in 2010.

The ASCEND study oversight bodies consist of a Steering Committee, Data Safety Monitoring Board and an Endpoint Committee consisting of highly experienced and well respected nephrologists, cardiologists and diabetologists.

Professor Giancarlo Viberti, Chairman of the ASCEND Steering Committee, stated: “SPP301 offers a truly novel approach to treating diabetic kidney disease. The clinical results obtained so far are very encouraging, and suggest that SPP301 could impact on morbidity and mortality in patients suffering from this chronic disease. We look forward to working with our colleagues worldwide on this large and rigorous study to demonstrate the benefits of SPP301 over current therapies.”

The Steering Committee members are professors Giancarlo Viberti, Johannes Mann, Luis Miguel Ruilope and Kenneth Jamerson.

Giancarlo Viberti is professor of diabetes and metabolic medicine at Kings College London, England. Professor Viberti was head investigator of the Microalbuminuria Collaborative Study Group and is Co-chairman of the Steering Committee for the ROADMAP (Randomised Olmesartan And Diabetes MicroAlbuminuria Prevention) study.

Johannes Mann is professor of medicine and director of the department of nephrology at the Schwabing General Hospital in Munich, Germany. Professor Mann was principal investigator for the HOPE (ramipril in Heart Outcomes Prevention Evaluation) study.

Luis Miguel Ruilope is associate professor of internal medicine at the Complutense University of Madrid, Spain, and head of the hypertension unit at the 12 de Octubre Hospital in Madrid. Professor Ruilope was chairman of the Endpoint Committee of the VALUE (Valsartan Antihypertensive Long-term Use Evaluation) study.

Kenneth Jamerson is professor of internal medicine at the University of Michigan, USA. Professor Jamerson was one of the lead investigators of the AASK (African American Study of Kidney disease and hypertension) study sponsored by the National Institute of Health.

The ASCEND study with SPP301 is being managed by Speedel and run globally by Quintiles, the world’s leading pharmaceutical services organization. Quintiles has considerable experience in the execution of studies related to diabetes; over the past 5 years it has worked on over 100 such studies, enrolling over 40,000 patients at over 5,500 clinical sites.

About SPP301

SPP301 is a once daily oral endothelin A receptor antagonist that Speedel licensed from Roche in October 2000 when it was in regulatory toxicology studies. SPP301, a second generation ERA, developed out of Roche's endothelin research and drug discovery program, and was specifically optimised for improved liver safety. Speedel has taken 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 results of which were announced in March 2005. Speedel has exclusive worldwide development and commercialisation rights under the licensing agreement with Roche.

About Diabetic Nephropathy

Diabetic Nephropathy is a new indication for this class of compound, 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. 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).

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 (>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.

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.

About Speedel

Speedel is a 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), the first-in-class renin inhibitor, is partnered with Novartis for Phase III development and commercialisation in hypertension with filing for registration expected in 2006. Our pipeline covers three different modes of action, and in addition to SPP100, includes SPP301 in Phase III, SPP200 in Phase II, SPP630 and SPP635 in early 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 60 employees, including 34 experienced pharmaceutical scientists, is located at our headquarters and laboratories in Basel, Switzerland and at offices in New Jersey, USA and Tokyo, Japan. Since being founded in 1998 as a private company, we have raised gross proceeds of CHF 169 million (approximately EUR 109 million or USD 141 million) from private placements of equity securities and a convertible loan and we have had total revenues, principally from milestone payments, of CHF 57.7 million (approximately EUR 37 million or USD 48 million).

(1) Avosentan on doubling of Serum Creatinine, End stage renal disease and death in Diabetic nephropathy

(2) Decision Resources, October 2004, based on research in US, Japan, France, Germany Italy, Spain, United Kingdom

(3) Those patients with the more advanced form of the disease, producing urinary albumin excretion of over 300mg per 24 hours

(4) Fast-Track Designations granted by the FDA facilitate the development and expedite the review of new drugs that are intended to treat serious or life-threatening diseases. In addition, it demonstrates the potential to address unment medical needs.

(5) Special Protocol Assessment is a procedure where FDA evaluates protocols of pivotal studies to ensure that the study design is adequate to meet scientific and regulatory requirements for a successful approval of an NDA

(6) Diabetes Care, American Diabetes Association 2004

(7) Diabetes Care, American Diabetes Association 2004

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.

For further information please contact

Nick Miles

Director Communications & Investor Relations


Hirschgässlein 11

CH - 4051 Basel


T +41 (0) 61 206 40 00

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F +41 (0) 61 206 40 01

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Frank LaSaracina

Managing Director

Speedel Pharmaceuticals Inc

1661 Route 22 West

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Bridgewater, NJ 08807

United States of America

T +1 732 537 2290

F +1 732 537 2292

M +1 908 338 0501

E [email protected]


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