Actelion Pharmaceuticals Ltd : Actelion provides update on Phase III GRIPHON study with selexipag in pulmonary arterial

 Actelion Pharmaceuticals Ltd : Actelion provides update on Phase III GRIPHON
  study with selexipag in pulmonary arterial hypertension - Study continues

Actelion Pharmaceuticals Ltd / Actelion provides update on Phase III GRIPHON
study with selexipag in pulmonary arterial hypertension - Study continues .
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ALLSCHWIL, SWITZERLAND -  08 May  2013 -  Actelion Ltd  (SIX: ATLN)  announced 
today that the Independent  Data Monitoring Committee  (DMC) has informed  the 
company of  its unanimous  recommendation to  continue the  pivotal Phase  III 
study,  GRIPHON.  In  addition  the   DMC  had  no  recommendations  for   any 
modification in study design or procedures.

The placebo-controlled, randomized GRIPHON study  is designed to evaluate  the 
efficacy and safety  of selexipag  in 1'150 patients  with pulmonary  arterial 
hypertension (PAH) in an event-driven morbidity/mortality study.

Selexipag is an  orally available selective  IP receptor agonist  that - in  a 
Phase II  study  -  showed  a  significant  reduction  in  pulmonary  vascular 
resistance  (PVR).  Pulmonary  arterial  hypertension  (PAH)  is  a   syndrome 
characterized by a progressive increase in pulmonary vascular resistance.

As described in the study protocol,  the GRIPHON DMC was scheduled to  perform 
an  interim  analysis   at  around   two  thirds  of   the  overall   foreseen 
morbidity/mortality events were  observed, in  addition to  the evaluation  of 
patient safety in the study.  The goal of the  interim analysis was to  assess 
whether study continuation  was warranted  based on the  primary objective  of 
demonstrating morbidity/mortality benefits.

With the interim analysis now successfully concluded and the DMC  recommending 
study continuation as planned, final study results of this event-driven  study 
are now expected by mid-2014.



                                     ###

Notes to Editor:

ABOUT GRIPHON

GRIPHON,  (Prostacyclin  (PGI2)   Receptor  agonist   in  pulmonary   arterial 
hypertension)  is  a   multicenter,  double-blind,  placebo-controlled   trial 
evaluating the long-term  efficacy and  safety of oral  selexipag in  patients 
with pulmonary arterial hypertension.

GRIPHON is close  to full enrollment  with 1'143 patients  randomized, of  the 
targeted 1'150, and represents the largest randomized, controlled study in PAH
patients. This pivotal study is designed to demonstrate a reduction in risk of
morbidity/mortality events  of selexipag  treatment  compared to  placebo  and 
evaluate the safety of the selexipag in PAH patients. Results are expected  to 
be available mid-2014.

ABOUT SELEXIPAG

Selexipag, originally  discovered and  synthesized by  Nippon Shinyaku,  is  a 
first-in-class, potent,  orally  available,  selective  IP  receptor  agonist. 
Selexipag has  major potential  as  a novel  treatment of  pulmonary  arterial 
hypertension.[1,2,4]

Results of  a Phase  II, 43-patient,  placebo-controlled, double-blind  study, 
where patients were randomized in a  3:1 ratio receiving selexipag or  placebo 
on top of  PDE5 and/or ERA,  showed a statistically  significant reduction  in 
pulmonary vascular  resistance (PVR;  primary parameter  for the  study).  The 
treatment effect was shown to be 30.3% after 17 weeks of treatment (p=0.0045).
Results also  showed an  encouraging numerical  improvement in  6-minute  walk 
distance (6MWD), which was a secondary  endpoint of this trial. Selexipag  was 
well  tolerated  and  the  safety  profile  was  in-line  with  the   expected 
pharmacologic effect. [3]

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  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 controlled 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.

ABOUT PROSTACYCLIN

Prostacyclin and prostaglandins  are types of  prostanoids. Endothelial  cells 
produce several vasoactive chemical factors, among them prostacyclin (PGI[2]),
which induce  vasodilation 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.

ABOUT PROSTACYCLIN RECEPTOR AGONISM

The IP  receptor  (PGI[2]  (prostacyclin)  receptor) is  one  of  5  types  of 
prostanoid   receptor   available   to   prostanoid   replacement   therapies. 
Prostacyclin activates the  IP receptor inducing  vasodilation and  inhibiting 
proliferation of  vascular smooth  muscle cells.  With selective  IP  receptor 
agonism, the risk of side effects  mediated by activation of other  prostanoid 
receptors may be minimized.

Actelion is  developing  a  first-in-class,  orally  available,  selective  IP 
receptor agonist that mimics  the actions of  endogenous prostacyclin for  the 
treatment of PAH.

ABOUT THE ACTELION / NIPPON SHINYAKU ALLIANCE

Actelion and Nippon Shinyaku entered  into an exclusive worldwide alliance  in 
April 2008  to collaborate  on selexipag,  a first-in-class  orally-available, 
selective IP receptor agonist for  patients suffering from pulmonary  arterial 
hypertension (PAH). This compound was originally discovered and synthesized by
Nippon Shinyaku.  Phase II  evaluation has  been completed,  and a  Phase  III 
program in PAH patients has been initiated. Actelion is responsible for global
development and commercialization  of selexipag outside  Japan, while the  two 
companies will co-develop and co-commercialize in Japan. Nippon Shinyaku  will 
receive milestone payments based on development stage and sales milestones  as 
well as royalties on any sales of selexipag.

References

1.Kuwano et al. NS-304, an orally available and long-acting prostacyclin
    receptor agonist prodrug. J Pharmacol Exp Ther 2007;322:1181-1188.
    
2.Kuwano et al. A long-acting and highly selective prostacyclin receptor
    agonist prodrug, NS-304, ameliorates rat pulmonary hypertension with
    unique relaxant responses of its active form MRE-269 on rat pulmonary
    artery. J Pharmacol Exp Ther 2008;326:691-699.
    
3.Simonneau G, Lang I, Torbicki A, Hoeper MM, Delcroix M, Karlocai K, Galie
    N. Selexipag, an oral, selective IP receptor agonist for the treatment of
    pulmonary arterial hypertension Eur Respir J 2012; 40: 874-880
    
4.Mubarak KK. A review of prostaglandin analogs in the management of
    patients with pulmonary arterial hypertension. Respir Med 2010;104:9-21.
    

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 2,300  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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