SPP100 (TEKTURNA/RASILEZ) DECREASES PROTEINURIA IN DIABETIC PATIENTS
- BENEFITS OF RENIN INHIBITORS ON TOP OF STANDARD THERAPY-
Basel/Switzerland and Bridgewater NJ/USA, 5 November 2007
Speedel Holding Ltd (SWX: SPPN) today welcomes the promising results
of SPP100 (Tekturna/Rasilez[1]) in the AVOID[2] Phase III clinical
trial with diabetic patients which were presented on 4 November at
the American Society of Nephrology Renal Week Congress in San
Francisco, California by Professor Hans-Henrik Parving of the
Department of Endocrinology, Righospitalet, Copenhagen, Denmark. The
study was sponsored by Novartis and the results show that SPP100, the
first-in-class direct renin inhibitor, further lowers proteinuria in
diabetic patients, independent of blood pressure, when administered
on top of losartan (ARB[3]), a standard therapy used to treat
diabetic kidney disease.
SPP100 was approved by the US Food and Drug Administration (FDA) in
the US in March 2007 under the trade name Tekturna and by the
European Union under the trade name Rasilez in August 2007 to treat
hypertension both as monotherapy and in combination with other
anti-hypertensives. Novartis announced in July 2007 that it was also
approved in Switzerland. Speedel successfully developed SPP100
through Phase I and II clinical trials before Novartis exercised its
license-back option in 2002.
Dr. Alice Huxley, CEO, said: "We are encouraged by the potential of
this novel class of therapy to provide patients with benefits over
and beyond blood pressure lowering. High blood pressure is a
co-morbidity found in 74% of diabetes patients[4] and it is clear
that new therapies are required to treat this vulnerable patient
population. These AVOID study results highlight the possible
long-term benefits of using renin inhibitors. Our next generation
compounds are specifically designed to further enhance the effects on
proteinuria, as we have demonstrated in our preclinical research."
AVOID study results[5]
599 patients were enrolled in this multi-national, randomised, double
blind Phase III study. There was a 3-months open-label run-in period
with patients receiving losartan 100 mg once per day (OD) in addition
to optimal antihypertensive therapy. After these 3 months, patients
were randomised to receive 6-months treatment with placebo or
aliskiren (150 mg OD for 3 months followed by forced titration to 300
mg OD for another 3 months) on top of losartan. The primary outcome
was reduction in early morning urinary albumin creatinine ratio
(UACR) from baseline to end of study. UACR is a widely accepted
biomarker for measuring the health of a patient's kidneys, and
reductions in albuminuria are associated with improved renal function
and decreased risk of end stage renal disease.[6]
SPP100 (aliskiren) provided a significant 20% reduction in mean UACR
on top of standard therapy compared with placebo after 24 weeks (p=
0.0009, 95% CI: 9-30) and aliskiren also significantly reduced mean
urinary albumin excretion rate (UAER) by 21% compared to placebo
(p=0.009; 95% CI: 5-30). The number of patients with 50% reduction in
UACR at the end of the study was 24.7% for aliskiren treated patients
versus 12.5% for placebo (p = 0.0002).
Estimated glomerular filtration rate (eGFR) was preserved by
aliskiren during the study. Blood pressure was similar between the
two treatment groups and remained controlled throughout the study;
changes in albuminuria did not correlate to changes in blood
pressure. The total number of adverse events and serious adverse
events was similar in the two groups. Single-measurement
serum-potassium 6.0mEq/L occurred in 4.7% vs. 1.7% (difference not
significant) in the aliskiren and placebo groups respectively.
The AVOID study is the second of a series of trials in ASPIRE HIGHER,
an extensive ongoing clinical programme by Novartis studying the
'beyond blood pressure' benefits of SPP100 due to direct renin
inhibition. Data in patients with heart failure (ALOFT[7]) were
presented earlier this year.
ALTITUDE[8] study commenced to determine long-term benefits of
aliskiren
SPP100 is not currently indicated for the treatment of diabetic
kidney disease. Novartis is currently recruiting for the ALTITUDE
Phase III clinical trial to investigate whether the addition of
aliskiren to conventional therapy provides additional cardio and
reno-protection in patients with type 2 diabetes. The study is event
driven and will conclude when about 1628 patients meet the primary
endpoint, which is estimated to take about 4 years.
Next generation renin inhibitors
With three new renin inhibitors in clinical development, Speedel
continues to build its mature pipeline by leveraging its expertise
and experience in renin inhibition. This novel mode of action has
been validated by the 2007 approval of SPP100 (Tekturna/Rasilez) in
the US, EU and Switzerland where it is marketed by Novartis in these
markets. Both Speedel and Novartis recently won the Wall Street
Journal Gold Award for Technology Innovation, which was given to the
companies for their work in discovering and developing SPP100 as an
innovative therapy for hypertension. Speedel is developing a family
of next generation renin inhibitors, and now has three compounds in
the clinic: SPP635 in Phase IIa, SPP676 in Phase I and SPP1148 in
Phase I.
Growing global health risks of high blood pressure
The Lancet published an editorial on 17 August 2007 which stated
that: "The risk of becoming hypertensive during lifetime exceeds a
staggering 90% for a person in a developed country." The editorial
also observed that: "The increasingly common combination and
interaction of obesity, diabetes, hyperlipidaemia and high blood
pressure, if left untreated for too long, leads to cardiovascular
disease, stroke, renal failure, dementia, and ultimately death.
Worldwide, the estimated number of adults with hypertension was 972
million in 2000; 639 million live in developing countries. By 2025,
the total number is expected to increase to 1.56 billion."[9]
About SPP100 (aliskiren, Tekturna/Rasilez[10] )
SPP100 (aliskiren, Tekturna/Rasilez) 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), 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.
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.
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 (Stanton, Jensen,
Nussberger, O'Brien, Hypertension.2003; 42: 1137-1143).
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 (Tekturna/Rasilez[11] ), 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
three different modes of action, and in addition to SPP100, includes
SPP301 in Phase II, SPP200 in Phase II, SPP635 in Phase Il, SPP1148
and SPP676 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 January 2007 the company raised gross proceeds of CHF 55.5 million
(approximately EUR 34.3 million or USD 44.5 million) through a
convertible bond issue. 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. Previously,
as a private company, we raised gross proceeds of CHF 255 million
(approximately EUR 157 million or USD 204 million) from private
placements of equity securities and two convertible loans including
the conversion premiums. 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 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.
- Ends -
[1] Tekturna/Rasilez® are Novartis trademarks
[2] Aliskiren in the Evaluation of PrOteinuria In Diabetes
[3] Angiotensin II receptor antagonists
[4] Selby JV et al. Am J Manage Care 2004: 10:163-70
[5] Parving H-H et al. AVOID Aliskiren in the Evaluation of
Proteinuria in Diabetes. Oral presentation at American Society of
Nephrology Renal Week Congress in San Francisco, California, November
2007. Poster SA-P01051
[6] GISEN group, Lancet 1997: 349:1857-63; de Zeeuw et al, Kidney Int
Suppl 2004: (92) S2-S6
[7] McMurray J et al. ALOFT - a 12 week safety evaluation of
aliskiren 150 mg vs. placebo when added to standard therapy for
stable heart failure. Oral presentation in Hotline I session at
European Society of Cardiology Congress 2007
[8] ALiskiren Trial In Type 2 diabetes Using cardio-renal Disease
Endpoints
[9] The Lancet: 2007; 370:539
[10] Tekturna/Rasilez® are Novartis trademarks
[11] Tekturna/Rasilez® are Novartis trademarks
For further information please contact
Nick Miles
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) 79 446 25 21
E nick.miles@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