- Robust efficacy and safety data presented at European Society of
Hypertension meeting -
BASEL, Switzerland and BRIDGEWATER, N.J., June 13 /PRNewswire-FirstCall/ -- Speedel (SWX: SPPN) is very pleased with the Phase III clinical data on SPP100 (Rasilez(1) in the treatment of hypertension in diabetic patients presented today by Novartis in Madrid at the 16th Meeting of the European Society of Hypertension (ESH). The data demonstrated the robust efficacy and good safety profile of SPP100 as a monotherapy and in co-administration with ramipril, an ACE(2) inhibitor. SPP100 is the first-in-class once daily oral renin inhibitor that Speedel successfully developed through Phase I and II clinical trials before Novartis exercised its license-back option in 2002. The U.S. Food and Drug Administration (FDA) in April 2006 accepted for review Novartis' new drug application (NDA) for SPP100 as a treatment for hypertension both as monotherapy and in co-administration with other anti-hypertensives.
Dr. Jessica Mann, Speedel Medical Director, said: "This new data underlines the potential of SPP100 in diabetic hypertensives, a segment of the hypertension population which is at a higher risk of having cardiovascular events than those hypertensive patients without diabetes. SPP100 offers additional blood pressure control and is well tolerated when co-administered with ramipril -- this is critical given that so many patients, especially those with hypertension and diabetes, are taking combination treatments in order to reach blood pressure targets."
The ESH meeting in Madrid is the first time that this data on SPP100 (Rasilez) has been presented in a scientific forum in Europe. The data presented today were from a clinical trial in 837 patients with diabetes and hypertension. Such patients are at an increased cardiovascular risk and the American Diabetes Association (ADA) recommends a lower blood pressure (BP) goal (< 130/80 mmHg) than patients with hypertension but without diabetes. In order to achieve such BP targets, most patients require therapy with multiple antihypertensive therapies. The use of SPP100 together with the ACE inhibitor ramipril (a first line therapy recommended by the ADA), not only decreases blood pressure further than ramipril alone through its additive effects, but also shows sustained 24-hour blood pressure control in these patients.
The number of adults with diabetes in the world is estimated to increase from 135 million in 1995 to 300 million in the year 2025(3).
The data from the Phase III clinical trial was presented today by investigators in the format of two posters:
SPP100 has greater BP lowering effect than ramipril and additional BP lowering effect when combined with ramipril in patients with diabetes and hypertension(4):
* After 8 weeks treatment, co-administration therapy with SPP100 and
ramipril provided superior reductions in MSDBP(5) from baseline compared
with either monotherapy
* By week 8, MSSBP(6) reductions from baseline were significantly greater
with both SPP100 monotherapy and SPP100/ramipril co-administration
therapy compared with ramipril monotherapy
* By the end of the study significantly more patients had responded to
SPP100 monotherapy and to SPP100/ramipril co-administration therapy than
ramipril monotherapy
* Co-administration therapy provided a clinically relevant additional BP
reduction of 4.6/2.1 mmHg over that achieved with standard ACE-I
treatment
* All treatments were well tolerated. As expected, the incidence of cough
was lower with SPP100 as a monotherapy than with ramipril. With
co-administration therapy the incidence of cough was lower than with
ramipril alone -- an unanticipated result that suggests an attenuation
of ACE-I induced cough
Adding SPP100 to ramipril improves 24-hour BP control compared to ramipril alone in patients with diabetes and hypertension(7):
* All treatments provided effective 24-hour BP lowering from baseline,
with SPP100/ramipril co-administration therapy providing significantly
greater ADBP(8) lowering than ramipril monotherapy
* Smoothness indices indicate that SPP100 monotherapy and SPP100/ramipril
co-administration therapy provide BP lowering from baseline with less
variability over the 24 hour period than ramipril alone
* Reductions from baseline in BP during the early morning BP surge were
greater with SPP100 monotherapy and SPP100/ramipril co-administration
therapy than with ramipril alone, suggesting that SPP100 based regimens
may provide greater protection for patients during the early morning
period of increased cardiovascular risk
Speedel believes that SPP100 has a five year lead over the next generation of renin inhibitors being developed in the industry. Speedel's own family of renin inhibitors includes SPP635 currently in Phase I with results due in the second half of 2006, followed by the SPP1100 series currently in toxicology testing with a compound due for entry into man before the end of 2006, and the SPP800 series currently in late-stage pre-clinical profiling.
About SPP100 (aliskiren, Rasilez(9)
SPP100 (aliskiren, Rasilez) is the first-in-class oral renin inhibitor. The development of SPP100 is the result of over 20 years of research on renin. Renin is the key 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.
Inhibition of renin, articulated as Plasma Renin Activity (PRA) is believed to be very important in end-organ protection (e.g. heart and kidney). PRA is a surrogate marker for several cardio-renal diseases, such as myocardial infarction and chronic renal disease. A renin inhibitor can lower PRA efficiently whereas most current leading anti-hypertensive drug classes such as diuretics, 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 in March 2004 Novartis started trials with SPP100 in Phase III as monotherapy for hypertension and in Phase IIb as combination therapy. Phase III trials are ongoing in the US, EU, and Japan, with first regulatory submission in the US already filed in Q1 2006 and planned in the EU during 2006.
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 starting dose of this ARB (Stanton, Jensen, Nussberger, O'Brien, Hypertension.2003; ).
About Hypertension
Hypertension is a major risk factor for heart disease and the main risk factor for stroke and heart attack, and can also lead to heart and kidney failure, so-called "end-organ damage". This disease is estimated to affect approximately 190 million people in the seven key markets (United States, Japan, Germany, France, United Kingdom, Italy and Spain), representing the largest indication for prescription pharmaceuticals worldwide, with approximately USD 39 billion in global annual sales in 2004, according to Datamonitor, IMS Health and Business Insights.
Hypertension is a common disorder in which blood pressure is abnormally high, placing undue stress on the heart, blood vessels and other organs such as the kidney and the brain. Blood pressure is determined in two phases as the heart contracts and relaxes. Systolic blood pressure represents the force that blood exerts on the walls of arteries as the heart contracts to pump out blood. Diastolic blood pressure represents the force as the heart relaxes to allow the blood to flow into the heart.
Due to its wide prevalence and impact on cardiovascular health, hypertension is a major cause of disease and death in Europe and North America. More than one in three Europeans and North Americans over the age of 35 suffers from hypertension -- but for the vast majority of patients who undergo hypertension treatment, the causes of high blood pressure are unknown. More than 40 % of patients undergoing treatment with current therapies do not reach targeted blood pressure levels, and so there is a considerable unmet medical need.
The latest potential therapeutic agents for hypertension are renin inhibitors. Renin is an enzyme produced in the kidneys in response to reduced renal perfusion. Through a cascade of biological events, renin acts to bring about sodium retention, an increase in blood pressure, and restoration of renal perfusion, which shuts off the signal for renin release. For hypertensive individuals, renin inhibitors are currently being investigated as a therapy that may provide benefits over current therapies to reduce blood pressure, decrease salt retention and may protect end organs such as the kidney, heart and brain.
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 (Rasilez), the first-in-class renin inhibitor, is partnered with Novartis for development and commercialisation in hypertension, and the NDA was filed with the FDA in the US in Q12006. Our pipeline covers three different modes of action, and in addition to SPP100, includes SPP301 in Phase III, SPP200 in Phase II, SPP635 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 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. As a private company, we have previously raised gross proceeds of CHF 239 million (approximately EUR 154 million or USD 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 USD 44 million). The company's shares were listed on the SWX Swiss Exchange under the symbol SPPN on 08 September 2005.
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) Rasilez (SPP100, aliskiren) is a Novartis trade name pending
regulatory, including FDA, approval
(2) Angiotensin-converting enzyme inhibitor (ACE-I)
(3) King H et al. Global burden of diabetes, 1995-2025: prevalence,
numerical estimates, and projections. Diabetes Care 1998:21(9):1414-
1431
(4) Study A2307 in 837 patients; Poster 269; Uresin Y, Taylor A, Kilo C,
Tschope D, Santonastaso M, Ibram G, Fang H, Satlin A
(5) Mean sitting diastolic blood pressure
(6) Mean sitting systolic blood pressure
(7) Study A2307 in 837 patients; Poster 268; Taylor A, Tschope D, Kilo C,
Ibram G, Fang H, Satlin A
(8) Ambulatory diastolic blood pressure
(9) Rasilez (SPP100, aliskiren) is a Novartis trade name pending
regulatory, including FDA, approval
SOURCE Speedel