Bosentan (Tracleer(R)) receives positive CHMP opinion for pediatric formulation

ALLSCHWIL, SWITZERLAND - 24 April 2009 - Actelion Ltd (SIX: ATLN)
announced today that the Committee for Medicinal Products for Human
Use (CHMP), the scientific committee of the European Medicines Agency
(EMEA), issued a positive opinion for the pediatric formulation of
bosentan (Tracleer(R)) for the treatment of pulmonary arterial
hypertension (PAH).

The CHMP recommended that the European Commission approves the new
dispersible 32mg tablet formulation of bosentan, which was
specifically developed for children, and which was studied in
children with PAH down to the age of two years in the pediatric
program. The European Commission is expected to make a final decision
within two months. Actelion continues to work with authorities
world-wide, including the US, to authorize the new dispersible
formulation and to expand the PAH product information for bosentan
bringing the treatment age down to 2 years of age.

Bosentan is an oral, dual endothelin receptor antagonist, which is
already approved as Tracleer(R) in Europe for the treatment of PAH; in
WHO functional class III PAH to improve exercise capacity and
symptoms and in PAH WHO Functional Class II where some improvements
have also been shown [1]. In the EU, Tracleer(R) is also indicated to
reduce the number of new digital ulcers in patients with systemic
sclerosis and ongoing digital ulcer disease.

PAH is a severe condition in children with an estimated median
survival of 10 months, if left untreated, after diagnosis [2].
Currently, no drug is indicated for the treatment of PAH in children
below 12 years of age; once licensed, bosentan will be the only PAH
treatment with a pediatric formulation.

The pediatric program investigated the, pharmacokinetics,
tolerability and safety of the new dispersible formulation of
bosentan. The safety profile was consistent with that seen in the
adult population.

The new, quadrisect, dispersible 32mg tablet formulation,
specifically developed for children above the age of 2 years, allows
for simple dose calculation and administration.

###

Notes to Editor:

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 [4] 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) [5]. 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 [5,6]. 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.

About PAH in Children
PAH is a severe condition in children with an estimated median
survival of 10 months after diagnosis, if left untreated [2].

Online information on PAH is available at www.pah-info.com.
PAH-info.com is part of an international PAH awareness campaign
supported by Actelion Pharmaceuticals and has been created to provide
information to healthcare professionals and patients.

About Tracleer(R) in Pulmonary Arterial Hypertension (PAH)
Tracleer(R) (bosentan), the first oral dual endothelin receptor
antagonist, is approved for the treatment of pulmonary arterial
hypertension (PAH) and made available by Actelion subsidiaries in the
United States, the European Union, Japan, Australia, Canada,
Switzerland and other markets worldwide.
Requires attention to two significant safety concerns: Potential for
serious liver injury (including rare cases of liver failure and
unexplained hepatic cirrhosis in a setting of close monitoring) -
Liver monitoring of all patients is essential prior to initiation of
treatment and monthly thereafter. Tracleer(R) treatment must not be
initiated in women of childbearing potential unless they practice
reliable contraception and participate in monthly pregnancy testing.
Due to these risks, Tracleer(R) is only supplied through a controlled
distribution.

About FUTURE-1
Pediatric FormUlation of bosenTan in pUlmonary arterial hypertension
(FUTURE-1) was an open-label, multicenter, non-controlled,
pharmacokinetic, safety and tolerability Phase III study. A new oral,
dispersible, quadrisected formulation of bosentan dedicated to
pediatric patients was investigated; patients received 2 mg/kg bid
for 4 weeks then 4 mg/kg bid until Week 12. The trial enrolled 36
patients aged 2 and <12 years with idiopathic PAH or familial PAH.

The main objective was to demonstrate that exposure to the pediatric
formulation of bosentan in children with PAH is similar to the known
exposure of the adult formulation. The primary study endpoint was
AUCtau of bosentan, determined at Week 12. Secondary objectives
included evaluation of tolerability and safety of bosentan in
pediatric patients with PAH. Secondary endpoints were safety
parameters and the additional pharmacokinetic parameters of Cmax and
Tmax. Exploratory endpoints included: changes from baseline to Week
12 in health-related quality of life, WHO functional class, and
Global Clinical Impression.

In FUTURE-1, the observed exposure to bosentan was similar to that in
children who participated in BREATHE-3 (who received the adult
formulation of bosentan). A subset of 11 patients had
pharmacokinetics evaluated after receiving both 2 and 4 mg/kg doses.
In these patients, exposure to bosentan was comparable at both doses:
geometric mean AUCtau was 3577 ng x h/mL and 3371 ng x h/mL with
bosentan 2 mg/kg and 4 mg/kg, respectively, and geometric mean Cmax
was 583 ng/mL and 649 ng/mL, respectively.

The safety and tolerability profile of bosentan was consistent with
that observed in previous placebo-controlled clinical trials in the
adult population.

An open-label safety extension, FUTURE-2, is ongoing to assess
long-term safety and outcome data.

About Tracleer(R) in Digital Ulcers (DU)
DUs are a manifestation of the underlying vasculopathy which is
central to the pathophysiology of systemic sclerosis (SSc) and
pivotal in the development of PAH in SSc, one of the leading causes
of death in SSc. Endothelin, a pathogenic mediator, is implicated in
the underlying vasculopathy in SSc.

DUs can be a frequent, persistent and debilitating complication of
SSc. They are caused by a reduction in the lumen of small bloody
vessels that decreases blood flow to the fingers and toes causing
open sores. DUs are painful, with a debilitating impact on patients'
daily life, often making it impossible to work and undertake even
simple day-to-day activities, particularly those associated with
fingertip function. Reducing the occurrence of new DUs is an
important and achievable treatment goal in SSc.

In the EU, Tracleer(R) is indicated to reduce the number of new digital
ulcers in patients with systemic sclerosis and ongoing digital ulcer
disease. Tracleer(R) has been shown to improve hand function (i.e.
dressing and hygiene) in patients with scleroderma-induced digital
ulcers.

Requires attention to two significant safety concerns [1]: Potential
for serious liver injury (including rare cases of liver failure and
unexplained hepatic cirrhosis in a setting of close monitoring) -
Liver monitoring of all patients is essential prior to initiation of
treatment and monthly thereafter. High potential for major birth
defects - Pregnancy must be excluded and prevented by two forms of
birth control; monthly pregnancy tests should be obtained. Because of
these risks, Tracleer(R) is only supplied through controlled
distribution.

References

1. Tracleer(R) SmPC.
2. D'Alonzo G et al. Survival in patients with primary pulmonary
hypertension. Annals of Internal Medicine 1991; 115:343-349.
3. Sitbon O et al. Long-term response to calcium channel blockers in
idiopathic pulmonary arterial hypertension. Circulation 2005;
111: 3105-3111.
4. Farber HW; Loscalzo J. Mechanisms of disease: pulmonary arterial
hypertension. N. Eng. J. Med. 2004; 351:1655-65.
5. Humbert M; Sitbon O; Simonneau G. Treatment of pulmonary arterial
hypertension. N. Eng. J. Med. 2004;351:1425-36.
6. 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.

Actelion Ltd
Actelion Ltd is a biopharmaceutical company with its corporate
headquarters in Allschwil/Basel, Switzerland. Actelion's first drug
Tracleer(R), an orally available dual endothelin receptor antagonist,
has been approved as a therapy for pulmonary arterial hypertension.
Actelion markets Tracleer(R) 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(R)).

For further information please contact:

Medical Media Contact
Elizabeth Perry
Packer Forbes
+44 208 772 1551
elizabeth@packerforbes.com

Investor Contact
Roland Haefeli
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
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;

SOURCE: Actelion Pharmaceuticals Ltd

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