Zavesca(R) (miglustat) receives EU approval for the treatment of progressive neurological manifestations in patients with Nieman

ALLSCHWIL/BASEL, SWITZERLAND - 29 January 2009 - Actelion Ltd (SIX:
ATLN)
announced today that Zavesca(R) (miglustat) has been approved in the
European Union for the treatment of progressive neurological
manifestations in adult patients and pediatric patients with
Niemann-Pick type C disease (NPC). Zavesca(R) is the first treatment to
be approved for patients with Niemann-Pick type C disease, a very
rare, invariably progressive and eventually fatal neurodegenerative
genetic disorder affecting both children and adults.

Zavesca(R) (100 mg miglustat) is already indicated for the oral
treatment of adult patients with mild to moderate type 1 Gaucher
disease. Zavesca(R) may only be used in the treatment of type 1 Gaucher
patients for whom enzyme replacement therapy is unsuitable.

Jean-Paul Clozel, M.D. and Chief Executive Officer of Actelion
commented: "I am very proud that Actelion - together with the
scientific community - has been able to demonstrate the role of
Zavesca(R) in reducing the progression of clinically relevant
neurological symptoms in patients with NPC. I would like to thank
both the patients and their families who, over the years, have been
involved in our clinical program with so much dedication, as well as
all the clinical experts for their continuous support. Actelion will
continue to support the rare disease community in its efforts to
advance science and medicine for the patient".

Ed Wraith, M.D., Royal Manchester Children's Hospital, commented:
"For the first time we have an approved therapy for NPC. The data on
the effects of treatment with Zavesca(R) obtained in a clinical trial
and in a retrospective cohort study consistently showed a favorable
clinical response. As a treating physician I am acutely aware of the
importance of reducing progression of neurological symptoms."

Regulatory proceedings to extend the use of miglustat in patients
with NPC are ongoing in other territories worldwide.

About Niemann-Pick type C disease
NPC is a very rare, fatal, neurodegenerative, genetic condition,
primarily affecting children and teenagers but which can strike at
any age. The symptoms are caused by the storage of some
glycosphingolipids within certain cells in the body, including the
brain. It is invariably progressive and most patients die within five
to ten years of diagnosis; for the majority the disease is fatal
during childhood. Neurological deterioration is the key feature of
the disease, and can manifest itself as clumsy body movements,
balance problems, slow and slurred speech, difficulty in swallowing,
problems with eye movements and seizures. Intellectual decline is
also common. In the final stages of the disease the child or young
adult is frequently bedridden, has little muscle control and is
intellectually impaired. Diagnosis of the disease can be difficult
and lengthy due to its rarity and heterogeneity. There is currently
no treatment option approved for this condition.

###

Notes to the editor

About Zavesca(R) and Niemann-Pick type C disease
Zavesca(R) is indicated for the treatment of progressive neurological
manifestations in adult patients and pediatric patients with
Niemann-Pick type C disease.

In order to gain approval for Zavesca(R) in Niemann-Pick type C
disease, a set of clinical data were obtained from one clinical trial
OGT918-007 and two multicenter retrospective cohort studies in
patients with NPC.

The usual dose of Zavesca(R) in adult NPC patients was 200 mg miglustat
three times a day, and was adjusted according to body surface area in
pediatric NPC patients.

In the clinical trial OGT918-007, adult and juvenile patients with
NPC (n=29, age >=12 years) were randomized to either miglustat 200 mg
t.i.d. (n=20) or standard of care (n=9) for 12 months [1]. In
addition, 12 children aged 4-12 years received miglustat at a dose
adjusted for body surface area. All patients were then given
miglustat for another 12 months. Horizontal saccadic eye movement
(HSEM) velocity was the primary endpoint. Other endpoints included
swallowing, ambulation, neurological examination, neuropsychological
assessment, tremor and quality of life. At 12 months, HSEM velocity
had improved in patients treated with miglustat versus those
receiving standard care; results were significant when patients
taking benzodiazepines were excluded (p=0.028) [1]. Children showed
an improvement in HSEM velocity of similar size at 12 months.
Improvement in swallowing capacity, stable auditory acuity, and a
slower deterioration in ambulatory index were also seen in treated
patients older than 12 years [1].

In an uncontrolled extension phase of the OGT918-007 trial, data
indicated that treatment with miglustat can provide disease
stabilization for important markers of neurological dysfunction in
NPC disease, both in the juvenile/adult and pediatric cohorts,
further strengthening the interpretation of a treatment effect of
miglustat observed at 12 months in the controlled phase of the trial
[2,3].

The safety and tolerability of miglustat 200 mg three times a day in
clinical trial participants was consistent with previous trials in
type 1 Gaucher disease, where half this dose was used [1, 2, 3].

A first retrospective cohort study was performed in 25 centers in 12
countries to assess data on changes of neurological status and
overall utility of treatment with miglustat in 66 NPC patients
receiving miglustat outside of the clinical trial OGT918-007 for a
mean duration of 1.5 years. A disease-specific disability scale was
used to evaluate the severity of dysphagia (swallowing), dystonia
(manipulation), ataxia (ambulation) and dysarthria (language
articulation) at diagnosis, treatment initiation and last visit [4].
A majority of patients remained at least stable after treatment with
regard to the four parameters, indicating that miglustat provides
clinically relevant benefits on neurological disease progression in
patients with NPC [4].

A second retrospective cohort study was performed in 7 centers in 6
countries to assess data on changes in neurological status in 57
patients not treated with miglustat during the natural course of the
disease for a mean duration of 5.5 years. The same disease-specific
disability scale was used to evaluate the severity of dysphagia,
dystonia, ataxia and dysarthria at the time of diagnosis until the
last visit. The results will be presented in the first half of 2009.

The benefit of treatment with Zavesca(R) for neurological
manifestations in patients with Niemann-Pick type C disease should be
evaluated on a regular basis, e.g. every 6 months; continuation of
therapy should be re-appraised after at least 1 year of treatment
with Zavesca(R).

About Zavesca(R) and type 1 Gaucher disease
Zavesca(R) (100 mg miglustat capsule) is indicated for the oral
treatment of adult patients with mild to moderate type 1 Gaucher
disease. Zavesca(R) may only be used in the treatment of type 1 Gaucher
patients for whom enzyme replacement therapy is unsuitable. It is
approved in the European Union, the United States, Canada,
Switzerland, Brazil, Australia, Turkey and Israel.

Zavesca(R) safety information
Gastrointestinal events, mainly diarrhea, have been observed in more
than 80% of patients treated with Zavesca(R), either at the onset of
treatment or intermittently during treatment. The majority of cases
are mild and are expected to resolve after the first weeks on
therapy. In clinical practice, diarrhea has been observed to respond
to diet modification (reduction of lactose and other carbohydrate
intake), to taking Zavesca(R) away from meals, and/or to antidiarrheal
medicinal products such as loperamide. In some patients, temporary
dose reduction may be necessary. Patients with chronic diarrhea or
other persistent gastrointestinal events that do not respond to these
interventions should be investigated according to clinical practice.
Zavesca(R) has not been evaluated in patients with a history of
significant gastrointestinal disease, including inflammatory bowel
disease.

Cases of peripheral neuropathy have been reported in patients treated
with Zavesca(R). Peripheral neuropathy seems to be more common in
patients with type 1 Gaucher disease compared to the general
population. All patients should undergo baseline and repeat
neurological evaluation. Patients who develop symptoms such as
numbness and tingling should have a careful re-assessment of risk
benefit.

Zavesca(R) may cause fetal harm if administered to a pregnant woman and
is contraindicated in women who are or who may become pregnant;
patients should be informed of the potential hazard to the fetus.
There is a risk of impaired fertility in men. Men should maintain
reliable contraceptive methods and not plan to conceive while taking
Zavesca(R) and for three months thereafter.

Reduced growth has been reported in some pediatric patients with
Niemann-Pick type C disease in the early phase of treatment with
Zavesca(R) where the initial reduced weight gain may be accompanied or
followed by reduced height gain. Growth should be monitored in
pediatric and adolescent patients during treatment with Zavesca(R); the
benefit/risk balance should be re-assessed on an individual basis for
continuation of therapy.

Mild reductions in platelet counts without association to bleeding
were observed in some patients with Niemann-Pick type C disease
treated with Zavesca(R). In patients included in the clinical trial,
40%-50% of patients had platelet counts below the lower limit of
normal at baseline. Monitoring of platelet counts is recommended in
these patients.

References
1. Patterson MC, Vecchio D, Prady H, Abel L and Wraith JE.
Miglustat for treatment of Niemann-Pick C disease: a randomised
controlled study. Lancet Neurol 2007; 6:765-772.
2. Patterson MC, Vecchio D, Prady H, Abel L and Wraith JE.
Miglustat for treatment of Niemann-Pick C disease: results of 24
month's treatment. Proceedings of 57th Annual meeting of the American
Society of Human Genetics, 2007; abstract # 2253.
3. Patterson MC, Vecchio D, Jacklin E and Wraith JE. Miglustat
in Niemann-Pick disease Type C (NPC): long-term data from a clinical
trial. Proceedings of 58th Annual meeting of the American Society of
Human Genetics, 2008; abstract # 766.
4. Pineda M, Wraith JE, Sedel F, et al. Miglustat in patients
with Niemann-Pick type C disease (NPC): a multicentre retrospective
survey. Journal of Inherited Metabolic Disease 2008; 31(Suppl 1) 98.
Note: this abstract describes the results of the survey with the
first 44 cases collected.

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 1900 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:
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,
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SOURCE: Actelion Pharmaceuticals Ltd

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