SPP100 (TEKTURNA/RASILEZ) DEMONSTRATES POTENTIAL TO PROTECT KIDNEYS
FROM DAMAGE
Potential kidney-protective benefits of SPP100 independent of proven
blood pressure reduction
Basel/Switzerland and Bridgewater NJ/USA, 4 June 2008
Data from the AVOID study published in this week's New England
Journal of Medicine demonstrate that the first-in-class direct renin
inhibitor Rasilez®1 (aliskiren), known as Tekturna®[1] in the US, may
have potential kidney-protective benefits that are independent of its
already proven ability to provide powerful blood pressure
reductions[2],[4]. AVOID is the first substantial clinical trial to
present data on potential kidney-protective benefits of Rasilez[1].
Damage to the kidneys caused by diabetes is the leading cause of
end-stage renal disease in developed countries, affecting more than
1.5 million people worldwide[2],[5].
In the AVOID study, Rasilez/Tekturna1 reduced albuminuria, a key
indicator of kidney disease, by an additional 20% in type 2 diabetic
patients with kidney disease who also had a diagnosis of high blood
pressure. These patients were already taking the maximum dose of the
angiotensin-receptor blocker (ARB) losartan, which has been shown to
slow the progression of diabetic kidney disease[2],[6].
In patients with diabetes, the first sign of kidney disease is the
presence of albumin in the urine, a condition called albuminuria[3].
Albuminuria is a key indicator of kidney disease and cardiovascular
disease[3]. Reducing albuminuria is associated with a reduction of
cardiovascular events[7] and slows the progression of kidney disease,
which can reduce the risk of chronic kidney failure in type 2
diabetic patients with kidney disease and high blood pressure[8],[9].
Dr. Thomas Littke, Head of Clinical Research & Development commented:
"Type 2 diabetic patients with high blood pressure are very fragile
patients. Importantly, SPP100 further lowered albuminuria by 20% in
these patients, independent of blood pressure, when administered on
top of losartan (ARB), a standard therapy used to treat diabetic
kidney disease. Albuminuria is an important indicator of kidney
disease and the level of albuminuria predicts cardiovascular
mortality in patients with diabetes".
Dr. Alice Huxley, CEO stated: "We are delighted that the published
data in the prestigious New England Journal of Medicine show the
potential of SPP100 (Rasilez/Tekturna[1]) in kidney protection. This
is very important for the future positioning of renin inhibition in
medical practice. Speedel's next generation renin inhibitors are
specifically designed to enhance the effects of lowering of
albuminuria to aid in kidney protection."
AVOID study results
In the 24-week AVOID study involving nearly 600 patients,
Rasilez/Tekturna[1] was added to the treatment regimen of type 2
diabetic patients diagnosed with high blood pressure who were already
receiving losartan and had albuminuria levels greater than 200
mg/g[2]. The study showed that overall Rasilez/Tekturna[1] (150 mg
increasing to 300 mg daily) reduced albuminuria by an additional 20%
when added to the maximum dose of losartan (100 mg)[2]. Furthermore,
a quarter of patients taking Rasilez/Tekturna added to losartan
experienced albuminuria reductions greater than 50% compared to those
patients taking losartan alone[2].
Data from AVOID further showed that Rasilez/Tekturna[1] added to the
maximum dose of losartan had similar rates of adverse events as the
placebo plus losartan group[2]. Hyperkalemia (elevated potassium
levels) was reported as an adverse event in 5.0% of patients taking
Rasilez/Tekturna1 in addition to losartan, compared to 5.7% of those
taking placebo plus losartan[2]. Hyperkalemia as a laboratory
abnormality was reported in 13.7% of patients taking
Rasilez/Tekturna[1] in addition to losartan compared to 10.8% of the
patients taking placebo plus losartan[2].
The AVOID study is one in a series of trials in the landmark ASPIRE
HIGHER clinical trial program, the largest ongoing cardio-renal
outcomes program, which involves more than 35,000 patients in 14
trials including three new mega-trials. The ASPIRE HIGHER program is
studying the effect of direct renin inhibition in a variety of
conditions, including diabetic kidney disease and heart
failure[2],[10].
About SPP100 (aliskiren, Tekturna/Rasilez[1])
SPP100 (aliskiren, Tekturna/Rasilez1) 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), a process leading
to high blood pressure and organ damage. 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. A first fixed-dose combination of
SPP100 and the diuretic HCT was approved in the US in January 2008.
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[11].
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, Aliskiren
(Tekturna/Rasilez[1])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 four different modes of
action, and in addition to SPP100, includes SPP301 (an endothelin A
receptor antagonist) in Phase II, SPP200 (a direct thrombin
inhibitor) in Phase II, the next generation renin inhibitors SPP635
(in Phase Il), SPP1148 and SPP676 (both in Phase I) and several
pre-clinical projects, including SPP2000 (aldosterone synthase
inhibitor).
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 80 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.
Speedel was founded in 1998 as a private company. In September 2005
the company's shares were listed on the SWX Swiss Exchange under the
symbol SPPN. Further information is available at www.speedel.com.
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] Parving H-H et al. Aliskiren Combined with Losartan in Type 2
Diabetes and Nephropathy. New England Journal of Medicine.
[3] National Institute of Diabetes and Digestive and Kidney Diseases.
National Kidney and Urologic Diseases Information Clearing House; NIH
Publication No. 06-4732. September 2006; www.kidney.niddk.nih.gov
[4] Tekturna® (aliskiren) Prescribing Information. Available at:
www.tekturna.com. Accessed 5 May 2008.
[5] Noble H. A concept analysis of renal supportive care: the
changing world of nephrology.
J Adv Nurses. 2007 Sep;59(6):644-53.
[6] Brenner B, Cooper M, de Zeeuw D, et al. Effects of losartan on
renal and cardiovascular outcomes in patients with type 2 diabetes
and nephropathy. N Engl J Med 2001; 245:861-869.
[7] de Zeeuw D, Remuzzi G, Parving H-H, et al. Albuminuria, a
therapeutic target for cardiovascular protection in type 2 diabetic
patients with nephropathy. Circulation. 2004;110:921-927.
[8] de Zeeuw D, Remuzzi G, Parving H-H, et al. Proteinuria, a target
for renoprotection in patients with type 2 diabetic nephropathy:
Lessons from RENAAL. Kidney International 2004; 65:2309-2320.
[9] Ibsen H, Olsen MH, Wachtell K, et al. Reduction in albuminuria
translates to reduction in cardiovascular events in
hypertensive patients: losartan intervention for endpoint reduction
in hypertension study. Hypertension 2005;45:198-202.
[10] Pitt B, McMurray J, Latini R, et al. Abstract 2491: Neurohumoral
Effects Of A New Oral Direct Renin Inhibitor In Stable Heart Failure:
The Aliskiren Observation Of Heart Failure Treatment Study (ALOFT).
Circulation.2007;116:II_549
[11] Stanton, Jensen, Nussberger, O'Brien, Hypertension.2003; 42:
1137-1143
For further information please contact
Dr. Harald F. Schaefer
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) 79 629 76 71
E harald.schaefer@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
