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Speedel Announces Breakthrough Phase II Data With SPP301 for Treatment of Diabetic Nephropathy

Posted on: Wednesday, 2 March 2005, 03:00 CST

BASEL, Switzerland and BRIDGEWATER, N.J., March 2 /PRNewswire/ -- Speedel announced today that SPP301, its once-a-day oral endothelin A receptor antagonist (ERA), has successfully completed Phase II clinical trials in the indication of diabetic nephropathy (diabetic kidney disease). Speedel has decided to take the drug candidate into Phase III, planned to start in the second half of 2005. Diabetic nephropathy represents a large and growing unmet medical need with a high mortality rate affecting an estimated 8.0 million people(1) diagnosed with diabetes in the US, Europe and Japan. 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. This breakthrough data reflects Speedel's commitment to producing innovative therapies for the treatment of cardiovascular and metabolic diseases. Speedel has in-licensed from Roche exclusive worldwide commercialisation and intellectual property rights to SPP301.

Dr. Alice Huxley, CEO of Speedel, commented: "This milestone is of major strategic importance for Speedel. We have decided that SPP301, which we believe to have a considerable potential to address an important unmet medical need, will be the first drug that we take through Phase III ourselves. Speedel's mature and diverse product pipeline in 2005 includes SPP100 Aliskiren partnered with Novartis in Phase III for hypertension and now SPP301 moving into Phase III for diabetic nephropathy."

Phase II results

In a Phase IIa clinical trial conducted by Speedel, clinically relevant efficacy with SPP301 was seen after 4 weeks treatment. SPP301 was tested in patients who were on high doses of angiotensin receptor blockers (ARBs), and decreased 24-hour proteinuria in a clinically relevant fashion.

For Phase IIb, Speedel conducted a double-blind, randomized, placebo- controlled trial in 286 diabetic nephropathy patients. Patients were randomized into five groups and received either escalating doses of SPP301 (5, 10, 25 or 50mg), or placebo, once daily on top of standard treatment, which consisted of either ACE (angiotensin converting enzyme) inhibitors in the majority of patients, or ARBs (angiotensin receptor blockers).

The primary endpoint was the change in albumin excretion rate (UAER) or proteinuria between baseline and the 12-week timepoint. In terms of efficacy, all dose groups of SPP301 showed a statistically significant decrease in UAER, compared to placebo. The decrease was greater in the two higher dose groups compared to the two lower dose groups. More importantly, SPP301 reduced proteinuria by over 30% on top of standard treatment for 55% of patients across all dose groups. The compound was generally safe and well tolerated at all four dose levels, and in particular has shown minimal liver toxicity, in contrast with earlier endothelin receptor antagonists.

According to Prof. Michael Weber (Professor of Medicine and Associate Dean for Research, State University of New York, Downstate Medical College), a member of Speedel's Medical Advisory Board: "These results demonstrate that SPP301 is able to reduce proteinuria by at least 30%. This is a remarkable additive effect in patients already receiving ACE inhibitors or ARBs, since these drugs are known to have strong proteinuria-reducing effects of their own. Importantly, data from the US National Kidney Foundation(2) suggest that these effects of SPP301 could impact morbidity and mortality in these patients with diabetic kidney disease. We believe that the good safety profile and efficacy of SPP301 over a 12-week period have provided a strong foundation for taking this compound into a full Phase III clinical trial that can explore the protective effects of this drug on the kidney and other major endpoints."

Phase III pivotal study

The Phase III pivotal morbidity and mortality study is expected to begin in the second half of 2005. It will be 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 2 diabetes patients with nephropathy. The study, which has been discussed and agreed with the FDA and the EMEA, will be conducted in Europe, USA and other countries and is expected to be complete within approximately 3.5 years. SPP301 has been granted Fast Track Designation by the FDA.

Speedel Medical Director, Jessica Mann M.D, PhD. added: "The prevalence of diabetic nephropathy has been increasing dramatically, in line with the rising numbers of diabetes patients worldwide. For those who develop diabetic nephropathy the therapeutic options are limited at present. Current treatments include 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 proven 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(3) We believe that SPP301 represents a great opportunity to develop a drug that could have significant medical benefits for a very large number of people who suffer from this disease."

About SPP301

SPP301 is a once daily oral endothelin A receptor antagonist that Speedel licensed from Roche in October 2000 when it was in preclinical toxicology studies. SPP301 developed out of Roche's leading position in endothelin research and strong drug discovery program and was specifically optimised to decrease liver toxicity. 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. In 2003 Speedel bought out Roche's option to license-back the compound upon completion of Phase IIb. Consequently, 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 macroalbuminuria (>300 mg urinary albumin per 24 hours), and to overt nephropathy. Later still, progressive renal functional decline is characterized by significant decreases in glomerular filtration rate, 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. About 20-40% of patients with type 1 or type 2 diabetes develop nephropathy(4) Current treatments (primarily antihypertensives and blood glucose control) 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 in 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 creates value for patients, partners and investors by developing innovative therapies for cardiovascular and metabolic diseases. Speedel is a world leader in renin inhibition, an exciting new approach to treating cardiovascular diseases. Our lead compound SPP100 (Aliskiren), a first-in-class renin inhibitor, is partnered with Novartis for Phase III development and commercialisation in hypertension. Our pipeline covers three different modes of action, and in addition to SPP100, includes SPP301 about to enter Phase III, SPP200 in Phase II, two compounds in Phase 0/Phase I plus several pre-clinical projects.

Speedel develops novel therapies 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 of primary-care indications, or we may ourselves complete Phase III for 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 sixty experienced pharmaceutical scientists and managers 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 secured CHF226.7 million (Euro 146.3 million or USD 188.9 million approx.) for investment in our pipeline through operating revenues, equity and a convertible loan.

(1) Decision Resources, October 2004

(2) 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

(3) Diabetes Care, American Diabetes Association 2004

(4) Decision Resources, October 2004

Forward looking statements

This press release contains certain forward looking statements that can be identified by the use of forward-looking terminology such as "envisaged", "potentially", and "could" or "may" etc. There are no guarantees that such future events or results will actually be realized, and in particular that the aforementioned licensing agreements or approaches will result in the development of a new drug for cardiovascular indications or any subsequent commercialisation of any product in any market. Any such commercial success can be affected by, among other things, uncertainties relating to product development, regulatory actions or delays or government regulation generally, the ability to obtain or maintain patent or other intellectual property protection and competition in general. Any of these and other factors can cause the actual results to differ materially from the expected or predicted results.

Speedel Pharmaceuticals, Inc.

CONTACT: Nick Miles, Director Communications & Investor Relations,Speedel, +41-0-61-206-40-00, direct, +41-0-61-206-40-14, fax,+41-0-61-206-40-01, mobile, +41-0-79-446-25-21, nick.miles@speedel.com, orFrank LaSaracina, Managing Director, Speedel Pharmaceuticals, Inc.,+1-732-537-2290, mobile, +1-908-338-0501, fax, +1-732-537-2292,frank.lasaracina@speedel.com

Web site: http://www.speedel.com/

Source: PRNewswire

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