Tracleer (bosentan) receives EU approval for pediatric formulation - the first and only licensed pulmonary arterial hypertension therapy for children

Corporate news announcement processed and transmitted by Hugin AS.
The issuer is solely responsible for the content of this
announcement.
----------------------------------------------------------------------
--------------

ALLSCHWIL, SWITZERLAND - 06 July 2009 - Actelion Ltd (SIX: ATLN)
announced today that the pediatric dispersible formulation of
Tracleer® (bosentan) for the treatment of pulmonary arterial
hypertension (PAH) in children has been approved in the European
Union.

This approval makes Tracleer® the only PAH therapy with an approved
pediatric formulation for treating children from two years of age.
PAH is a severe condition in children with an estimated median
survival of 10 months after diagnosis if left untreated [1].

Martine Clozel, M.D., Pediatrician and Chief Scientific Officer at
Actelion, commented: "Our team is very proud of this achievement. We
decided very early in the development of Tracleer® to devote time and
effort to the development of a formulation adapted to the daily
treatment of children suffering from PAH, even if it was representing
a small population. It has been a long, but ultimately extremely
rewarding journey, which had begun even before the first marketing
authorization of Tracleer®."

Isaac Kobrin, M.D. and Head of Clinical Development at Actelion,
added: "Having the approval of Tracleer®, with an accurate dosing in
a child-friendly form, is an important advancement in the treatment
of PAH in children. After receiving approval in the EU, we will
continue our regulatory filings in other countries to ensure that
children can benefit from this pediatric formulation of Tracleer® on
a worldwide basis."

Professor Maurice Beghetti, Head of the Pediatric Cardiology Unit at
Hôpital des Enfants, Geneva, commented: "It is great to see Actelion
leading the way in providing a treatment fully tailored for children,
from the precise dosing to the flavor. Ensuring correct dosing for
children is a challenge we face across all diseases but particularly
in orphan diseases that affect children. This pediatric formulation
for Tracleer® is a large step in the right direction towards
developing treatment with the needs of children specifically in
mind."

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

The new quadrisect, dispersible 32mg tablet formulation of bosentan,
which was specifically developed for children, allows a convenient,
accurate and more flexible dosing regimen according to low body
weight.

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

The key trials in the pediatric research program include:

* BREATHE-3 (Bosentan Randomized trial of Endothelin
Antagonist THErapy for pulmonary hypertension): an open-label study
that provided safety and efficacy data in children with PAH treated
with Tracleer® with or without concomitant prostanoid therapy. It
also provided important information on the dose required in the
pediatric formulation.

* FUTURE-1 (Pediatric FormUlation of bosenTan in pUlmonary
arterial hypeRtEnsion): an open-label study that evaluated the
safety and pharmacokinetics of a new dispersible tablet formulation
of Tracleer®. This study provided important pharmacokinetic and
dosing information using the new pediatric formulation of bosentan.
In FUTURE-1, the observed exposure to Tracleer® was similar to that
in children who participated in BREATHE-3.

* FUTURE-2: an open-label safety extension study is ongoing
to assess long-term safety and outcome data.

###

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 shown positive treatment effects in patients with 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 [1].

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® in Pulmonary Arterial Hypertension (PAH)
Tracleer® (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.

About Actelion's pediatric program
BREATHE-3 (Bosentan Randomized trial of Endothelin Antagonist THErapy
for pulmonary hypertension) an open-label study, provided safety and
efficacy data in children with PAH, treated with the adult
film-coated tablet formulation of Tracleer® with or without
concomitant prostanoid therapy. It also provided important
information on the dose required in the pediatric formulation.

In the BREATHE-3 study, WHO functional class improved in five of the
19 patients over the 12-week treatment period. Improvements were
observed in each weight group, and only one patient deteriorated;
13/19 remained stable. These clinical results were consistent with
those obtained in earlier studies conducted in adult patients and
support that pediatric patients with PAH may derive significant
clinical benefit from therapy with bosentan.

FUTURE-1 (Pediatric FormUlation of bosenTan in pUlmonary arterial
hypertension) an open-label study, evaluated the safety and
pharmacokinetics of a new dispersible tablet formulation of bosentan.
A new oral, dispersible, quadrisect tablet formulation of bosentan
dedicated to pediatric patients was investigated; patients initially
received 2 mg/kg bid for 4 weeks followed by 4 mg/kg bid until Week
12. The trial enrolled 36 patients aged from 2 years up to 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
AUC(tau) of bosentan, determined at Week 12. Secondary objectives
included evaluation of tolerability and safety of bosentan in
pediatric patients with PAH. Secondary endpoints included 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. A subset of 11 patients had
pharmacokinetics evaluated for both 2 and 4 mg/kg doses. In these
patients, exposure to bosentan was comparable at both doses:
geometric mean AUC(tau) 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® 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® is indicated to reduce the number of new digital
ulcers in patients with systemic sclerosis and ongoing digital ulcer
disease. Tracleer® 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 [2]: 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® is only supplied through controlled
distribution.

References
1. Widlitz A, Barst RJ. Pulmonary Arterial Hypertension in
children. Eur Respir J 2003;21:155-176.
2. Tracleer® SmPC.
3. Rosenzweig et al. Effects of long-term Bosentan in children
with pulmonary arterial hypertension. J. Am. Coll. Cardiol 2005;
46:697-704.
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®, 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:

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

Investor 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

--- End of Message ---

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;
Copyright © Hugin AS 2009. All rights reserved.