Actelion's macitentan meets primary endpoint in pivotal Phase III SERAPHIN outcome study in patients with pulmonary arterial hypertension
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Actelion Pharmaceuticals Ltd /
Actelion's macitentan meets primary endpoint in pivotal Phase III SERAPHIN
outcome study in patients with pulmonary arterial hypertension
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ALLSCHWIL/BASEL, SWITZERLAND - 30 April 2012 - Actelion (SIX: ATLN) announced
today that initial analysis indicates that the pivotal, long-term, event-driven
study SERAPHIN with macitentan, a novel dual endothelin receptor antagonist, in
742 patients suffering from pulmonary arterial hypertension (PAH) and treated
for up to three and a half years, has met its primary endpoint.
Macitentan, at both the 3 mg and 10 mg dose, decreased the risk of a
morbidity/mortality event over the treatment period versus placebo. This risk
was reduced by 45 percent in the 10 mg dose group (p<0.0001). At 3 mg, the
observed risk reduction was 30 percent (p=0.0108). Treatment with macitentan in
the SERAPHIN study was well tolerated.
Jean-Paul Clozel, M.D. and Chief Executive Officer of Actelion commented: "I am
extremely pleased with the outstanding SERAPHIN results. We are committed to
working with the Health Authorities to bring this potentially important
advancement in PAH to patients as soon as possible. Submission of the
registration dossier to Health Authorities worldwide is expected by the fourth
quarter of 2012."
Lewis J. Rubin, M.D., Emeritus Professor, University of California, San Diego
and Senior Advisor on SERAPHIN commented: "With this well-designed PAH study,
Actelion pursued an ambitious goal to focus on outcome benefits as the primary
endpoint. The impressive results of this landmark study are setting a new
standard in how to conduct studies in this devastating disease."
Gerald Simonneau M.D., Professor of Pneumology and Head of the Department of
Pulmonary Disease and Intensive Care Unit, Hospital Antoine Beclere-Clamart,
France and Senior Advisor on SERAPHIN commented: "As a physician with more than
30 years experience in the fight against this terrible disease, I am very
excited by the outcome of this study. These results represent an important
milestone in the history of clinical trials in PAH and show that macitentan has
the potential to offer a new treatment paradigm for these patients."
Secondary efficacy endpoints, including change from baseline to month 6 in six-
minute walk-distance, change from baseline to month 6 in WHO functional class
and time - over the whole treatment period - to either death due to PAH or
hospitalization due to PAH, also showed a dose-dependent effect (p<0.05 for
either dose). A trend in favor of 10 mg macitentan was observed on all-cause
mortality (p=ns).
Guy Braunstein, M.D. and Head of Global Clinical Development commented: "Our
thanks go to the investigators and their staff in almost 40 countries, who
participated in this compelling study. I truly believe that these results with
macitentan will translate into clinical benefits for patients suffering from
PAH. The Company will now rapidly analyze this largest ever clinical study in
PAH in full detail, in view of regulatory filings later this year."
Full data from this study will be made available through scientific disclosure
at upcoming congresses and publications.
About the safety and tolerability in SERAPHIN
The safety set comprised 741 patients (randomized 1:1:1), who received at least
one dose of study treatment. Mean exposure to study treatment was 85.3 weeks for
placebo patients (n=249), 99.5 weeks for patients on 3 mg (n=250) and 103.9
weeks for patients on 10 mg (n=242).
Macitentan in this patient population was well tolerated. The number of adverse
events reported and patients discontinuing treatment due to adverse events was
similar across all groups.
Elevations of liver alanine or aspartate aminotransferases greater than three
times the upper limit of normal were observed in 4.5 percent of patients
receiving placebo, in 3.6 percent of patients on 3 mg of macitentan and in 3.4
percent of patients on 10 mg of macitentan. In addition, no difference was
observed between macitentan and placebo on fluid retention (edema).
A decrease in hemoglobin - reported as an adverse event - was observed more
frequently on macitentan than placebo, with no difference in treatment
discontinuation between groups.
About the SERAPHIN study
SERAPHIN (Study with an Endothelin Receptor Antagonist in Pulmonary arterial
Hypertension to Improve cliNical outcome) was the largest randomized, controlled
study in PAH patients with a long-term treatment to include a clearly defined
morbidity/mortality primary end-point [1]. The pivotal Phase III study was
designed to evaluate the efficacy and safety of macitentan - a novel dual
endothelin receptor antagonist that resulted from a tailored drug discovery
process - through the primary endpoint of time to first morbidity and all-cause
mortality event in patients with symptomatic PAH.
Global enrollment was completed in December 2009 with a total of 742 patients.
Patients were randomized 1:1:1 to receive two different doses of macitentan (3
mg and 10 mg once daily) or placebo. Patients were allowed to receive PAH
background therapy throughout the study, either PDE-5 inhibitors or oral/inhaled
prostanoids. This event-driven study was conducted in 151 centers from almost
40 countries in North and Latin America, Europe, Asia-Pacific and Africa and was
completed in the first half of 2012, with 287 patients having an adjudicated
event.
About macitentan
Macitentan is a novel dual endothelin receptor antagonist that resulted from a
tailored drug discovery process. Macitentan has a number of potentially key
beneficial characteristics. i.e. increased in vivo preclinical efficacy vs.
existing ERAs resulting from sustained receptor binding and tissue penetration
properties. A clinical pharmacology program indicated a low propensity of
macitentan for drug-drug interactions [2, 3, 4].
About macitentan in other clinical development programs
Macitentan is currently investigated in a pivotal Phase III program in patients
with ischemic digital ulcers associated with systemic sclerosis, initiated in
December 2011. Additionally, following excellent preclinical results, a Phase
I/Ib open-label study was initiated with macitentan in patients with recurring
glioblastoma.
###
Notes to the Editor
About Pulmonary Arterial Hypertension
Pulmonary arterial hypertension (PAH) is a chronic, life-threatening disorder
characterized by abnormally high blood pressure in the arteries between the
heart and lungs of an affected individual. The symptoms of PAH are non-specific
and can range from mild breathlessness and fatigue during normal daily activity
to symptoms of right heart failure and severe restrictions on exercise capacity
and ultimately reduced life expectancy.
PAH is one group within the classification of pulmonary hypertension (PH). This
group includes idiopathic PAH, heritable PAH and PAH caused by factors which
include connective tissue disease, HIV infection and congenital heart disease.
The last decade has seen significant advances in the understanding of the
pathophysiology of PAH, which has been paralleled with developments of treatment
guidelines and new therapies. Drugs targeting the 3 pathways that have been
established in the pathogenesis of PAH are endothelin receptor antagonists
(ERAs), prostacyclins and phosphodiesterase-5 inhibitors. PAH treatments have
transformed the prognosis for PAH patients from symptomatic improvements in
exercise tolerance 10 years ago to delayed disease progression today. Improved
disease awareness and evidence-based guidelines developed from randomized
clinical trial data have highlighted the need for early intervention, goal-
oriented treatment and combination therapy.
Despite these advances in PAH, survival rates are unacceptably low and PAH
remains incurable.
References
1. For a general discussion of a clinically meaningful outcome end-point,
please see: Proceedings of the 4th world symposium on pulmonary
hypertension. J Am Coll Cardiol 2009;54(1 Suppl).
2. Sidharta PN et al. Macitentan: Entry-into-humans study with a new endothelin
receptor antagonist. Eur J Clin Pharmacol. 2011;67(10):977-84
3. Bruderer S et al. Effect of cyclosporine A and rifampin on the
pharmacokinetics of macitentan, a tissue-targeting dual endothelin receptor
antagonist. AAPS J. 2012;14(1):68-78.
4. Bruderer S et al. Absorption, distribution, metabolism, and excretion of
macitentan, a dual endothelin receptor antagonist, in humans. Epub Mar
30, 2012
For more information on Actelion's offerings in the area of PAH, please refer to
www.actelion.com
Actelion Ltd.
Actelion Ltd is a biopharmaceutical company with its corporate headquarters in
Allschwil/Basel, Switzerland. Actelion's first drug Tracleer®, an orally
available dual endothelin receptor antagonist, has been approved as a therapy
for pulmonary arterial hypertension. Actelion markets Tracleer through its own
subsidiaries in key markets worldwide, including the United States (based in
South San Francisco), the European Union, Japan, Canada, Australia and
Switzerland. Actelion, founded in late 1997, is a leading player in innovative
science related to the endothelium - the single layer of cells separating every
blood vessel from the blood stream. Actelion's over 2,500 employees focus on the
discovery, development and marketing of innovative drugs for significant unmet
medical needs. Actelion shares are traded on the SIX Swiss Exchange (ticker
symbol: ATLN) as part of the Swiss blue-chip index SMI (Swiss Market Index
SMI®).
For further information please contact:
Roland Haefeli
Senior Vice President, Head of Investor Relations & Public Affairs
Actelion Pharmaceuticals Ltd, Gewerbestrasse 16, CH-4123 Allschwil
+41 61 565 62 62
+1 650 624 69 36
www.actelion.com
The above information contains certain "forward-looking statements", relating to
the company's business, which can be identified by the use of forward-looking
terminology such as "estimates", "believes", "expects", "may", "are expected
to", "will", "will continue", "should", "would be", "seeks", "pending" or
"anticipates" or similar expressions, or by discussions of strategy, plans or
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and research and development programs and anticipated expenditures in connection
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may vary materially from those described herein as anticipated, believed,
estimated or expected.
Conference Call / Audiocast
Actelion Ltd will host a Conference Call / Audiocast on on Monday, 30 April
2012, at 14.00 CET / 13.00 BST / 08.00 a.m. EST.
Date/Time:
30 April 2012 14.00 - 15.00 Basel (CET)
13.00 - 14.00 UK (BST)
08.00 a.m. - 09.00 a.m. US (EST)
Conference Call Connect #:
Dial-in participants should start calling the number below 10-15 minutes before
the conference is due to start.
Dial: Europe: +41 (0)44 580 00 74
UK: +44 (0)203 367 94 53
US: +1 866 907 59 23
Participant's mode:
Listen-Only with possibility to open individual lines during Q&A session.
Participants will be asked for their Name and Company.
Audiocast Access:
Audiocast participants should visit the Actelion website www.actelion.com 10-15
minutes before the conference is due to start.
Participant's mode:
Listen only
Audiocast Replay:
The archived Investor Audiocast will be available for replay through
http://www.actelion.com approximately 60 minutes after the call has ended.
Press Release PDF:
http://hugin.info/131801/R/1607160/509716.pdf
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[HUG#1607160]
Unternehmensinformation / Kurzprofil:
Datum: 30.04.2012 - 07:00 Uhr
Sprache: Deutsch
News-ID 140345
Anzahl Zeichen: 15069
contact information:
Town:
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Kategorie:
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