Actelion's PGI2 receptor agonist demonstrates efficacy in pulmonary
arterial hypertension patients - Morbidity-Mortality Phase III study
to be initiated before year-end
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ALLSCHWIL, SWITZERLAND - 17 July 2009 - Actelion Ltd (SIX: ATLN)
announced today that positive data have been obtained in a Phase IIa
study with its first-in-class orally active non-prostanoid PGI2
receptor agonist in pulmonary arterial hypertension (PAH) patients.
In the 43 patient placebo-controlled double-blind study to assess
efficacy, safety and tolerability the primary endpoint of change from
baseline in pulmonary vascular resistance (PVR) was met with high
statistical significance (P<0.01). The compound was well tolerated in
the study.
Jean-Paul Clozel, M.D. and Chief Executive Officer of Actelion
commented: "Together with our partner Nippon Shinyaku, we are very
excited by the remarkable results we have seen in this study. I am
especially pleased as efficacy was achieved on top of background
therapy with either an endothelin receptor antagonist and/or a PDE-5
inhibitor. This efficacy with good tolerability makes us determined
to accelerate our development program."
The positive study results support advancing this first orally active
non-prostanoid PGI2 receptor agonist into Phase III. This approach
was previously discussed and agreed with the FDA while the study was
ongoing. Actelion will now rapidly approach the FDA to finalize the
design for a Phase III program with a morbidity/mortality endpoint.
Consequently, Actelion expects to initiate this program before
year-end.
Jean-Paul Clozel concluded: "For the last 30 years, the medical
community has been working towards a well-tolerated and effective
oral therapy stimulating the prostacyclin pathway. I am very hopeful
that in the not so distant future, our PGI2 receptor agonist will
make a significant contribution to therapy for this devastating
disease."
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Notes to Editor:
About the Phase IIa study
The study was a multicenter, double-blind, randomized,
placebo-controlled study evaluating efficacy and safety of ACT-293987
in PAH patients. The primary endpoint was pulmonary vascular
resistance. The study was completed in July 2009 with 43 patients
randomized 3:1.
About Pulmonary Arterial Hypertension (PAH)
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
function of the heart and lungs is severely compromised, manifested
by a limited exercise capacity, and, ultimately, a reduced life
expectancy. Approximately 100,000 people in Europe and the United
States are afflicted with either primary or secondary forms of the
disease related to conditions or tissue disorders that affect the
lungs, such as scleroderma, lupus, HIV/AIDS or congenital heart
disease.
PAH is associated with structural changes in both the pulmonary
vasculature and the right ventricle. Recent advances [1] in the
understanding of the pathogenic factors leading to the pulmonary
vascular disease have led to the development of new therapies
targeting specific pathways (the prostacyclin pathway; the endothelin
pathway; and the nitric oxide pathway) [2]. The available therapies
have positive effects in PAH, but they do not provide a cure, and in
many patients the disease will progress. PAH remains a serious
life-threatening condition [2,3]. Early recognition and an
understanding of the selection and timing of therapeutic options
remain critical elements in the optimal management of patients with
this disorder.
Prostacyclin
Endothelial cells produce several vasoactive chemical factors, among
them prostacyclin (PGI2), which induce vasodilatation of blood
vessels and inhibit smooth muscle cell proliferation and platelet
aggregation. The peptide endothelin is also produced by the
endothelium, and is a potent constrictor of blood vessels and
promotes cell proliferation. In a normal healthy state, prostacyclin
helps counter-balance the actions of endothelin. In certain disease
conditions, however, production of prostacyclin by the endothelium is
impaired, allowing the deleterious effects of excessive levels of
endothelin to predominate.
Prostacyclin receptor
Prostacyclin binds the prostacyclin receptor located on the surface
of platelets and vascular smooth muscle cells. The receptor is a
G-protein coupled receptor that, upon activation by prostacyclin,
stimulates the formation of cyclic adenosine monophosphate (cAMP).
Dysfunction of the prostacyclin system occurs in several
cardiovascular disorders, including thrombosis, myocardial
infarction, stroke, myocardial ischemia, atherosclerosis and
pulmonary arterial hypertension (PAH). Restoration of prostacyclin
function using prostacyclin analogues that activate IP receptors
improves prognosis for patients with PAH. Prostacyclin counteracts
the vasoconstrictor and pro-thrombotic activity of endothelin.
Actelion is developing an orally available and long-acting
non-prostanoid PGI2 receptor agonist that mimics the actions of
endogenous prostacyclin for the treatment of PAH.
References
1. Farber HW; Loscalzo J. Mechanisms of disease: pulmonary arterial
hypertension. N. Eng. J. Med. 2004; 351:1655-65.
2. Humbert M; Sitbon O; Simonneau G. Treatment of pulmonary arterial
hypertension. N. Eng. J. Med. 2004;351:1425-36.
3. Humbert M; Morrell NW; Archer SL; et al. Cellular and molecular
pathobiology of pulmonary arterial hypertension. J. Am. Coll.
Cardiol. 2004; 43: Suppl. 12: 13S-24S.
About the Actelion / Nippon Shinyaku alliance
Actelion and Nippon Shinyaku entered into an exclusive worldwide
alliance in April 2008 to collaborate on an orally-available
long-acting prostaglandin I2 (PGI2) receptor agonist for patients
suffering from pulmonary arterial hypertension (PAH). This compound
was originally discovered and synthesized by Nippon Shinyaku. Phase I
evaluation has been completed, and a Phase II program in PAH patients
was initiated by Nippon Shinyaku in Europe at the end of 2007.
Actelion will be responsible for global development and
commercialization of the PGI2 receptor agonist outside Japan, while
the two companies will co-develop and co-commercialize in Japan.
Nippon Shinyaku
For further information on Nippon Shinyaku please visit:
http://www.nippon-shinyaku.co.jp/english/index.html
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 2000 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
Vice President, Head of Investor Relations & Corporate Communications
Actelion Pharmaceuticals Ltd, Gewerbestrasse 16, CH-4123 Allschwil
+41 61 565 62 62
+1 650 624 69 36
http://www.actelion.com
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Actelion Pharmaceuticals Ltd
Gewerbestrasse 16 Allschwil
Switzerland
WKN: 936767; ISIN: CH0010532478; Index: SBIOM, SLIFE, SMCI, SMIEXP,
SMIM, SPI, SPIEX;
Listed: Main Market in SIX Swiss Exchange;
