Actelion Pharmaceuticals Ltd: Selexipag meets primary endpoint in pivotal Phase III GRIPHON outcome study in patients with

  Actelion Pharmaceuticals Ltd: Selexipag meets primary endpoint in pivotal
     Phase III GRIPHON outcome study in patients with pulmonary arterial
                                 hypertension

Actelion Pharmaceuticals Ltd / Selexipag meets primary endpoint in pivotal
Phase III GRIPHON outcome study in patients with pulmonary arterial
hypertension . Processed and transmitted by NASDAQ OMX Corporate Solutions.
The issuer is solely responsible for the content of this announcement.

ALLSCHWIL, SWITZERLAND  -  16 June  2014  -  Actelion Ltd  (SIX:  ATLN)  today 
announced the top-line results of the pivotal Phase III GRIPHON study in 1,156
patients with pulmonary arterial hypertension (PAH) with selexipag, the  first 
selective oral prostacyclin IP receptor  agonist. Initial analysis shows  that 
the event-driven outcome study has met its primary efficacy endpoint with high
statistical significance.

Selexipag decreased the risk of a morbidity/mortality event versus placebo  by 
39% (p<0.0001). Efficacy  observed was  consistent across  the key  subgroups; 
age, gender, WHO Functional  Class, PAH etiology  and background PAH  therapy. 
Patients were treated for up to 4.3 years. The overall tolerability profile of
selexipag in GRIPHON was consistent with prostacyclin therapies.

Jean-Paul Clozel, M.D. and Chief  Executive Officer of Actelion commented:  "I 
am overwhelmed by the  result of this long-term  outcome study that  evaluated 
selexipag in a setting where 80 percent of patients already received oral  PAH 
therapy at baseline. Together with our partner Nippon Shinyaku, we are now one
step closer to bringing an  effective oral therapy targeting the  prostacyclin 
pathway to the  PAH community.  We will now  work diligently  to complete  the 
analyses with  the  goal to  initiate  first regulatory  filings  with  Health 
Authorities as soon as possible."

Gérald Simonneau, M.D., Professor of Pulmonology and Head of the Department of
Pulmonary  Disease  and   Intensive  Care  Unit,   Université  Paris-Sud,   Le 
Kremlin-Bicêtre, France and Steering Committee member commented: "I have  been 
prescribing intravenous  prostacyclin therapies  in  PAH patients  for  almost 
twenty years. Today's GRIPHON results represent a major step forward. For  the 
first  time,  with  selexipag,  we  have  an  oral  compound  acting  on   the 
prostacyclin  pathway  showing  a  significant  risk  reduction  on  a  highly 
clinically relevant endpoint."

Guy Braunstein, M.D.  and Head  of Global Clinical  Development commented:  "I 
would like to thank  the PAH community for  their long-term commitment,  which 
made  this,  the  second  morbidity/mortality  outcome  study  from   Actelion 
possible. While  we are  just  beginning to  analyze  the data,  the  top-line 
results we  have  in  hand  today  are  already  impressive.  The  concept  of 
individualized  uptitration  of  selexipag   according  to  tolerability   was 
successful, with a consistent result seen across the entire dose range."

Vallerie McLaughlin M.D.,  Director of the  Pulmonary Hypertension Program  in 
the Divisionof Cardiovascular Medicine at the University of Michigan,  United 
States and Steering  Committee member  commented: "The  GRIPHON study  results 
hold the promise  that selexipag  might open  up the  prostacyclin pathway  to 
different groups of patients given the consistent efficacy findings across key
subgroups evaluated in this long-term outcome study. In addition, GRIPHON  has 
shown  once  again   that  registration   studies  that   follow  the   robust 
morbidity/mortality definitions - as  recommended by the  4^th and 5^th  World 
symposia on  Pulmonary Hypertension  -  have the  potential to  deliver  truly 
meaningful clinical information."

Detailed study results will be made available through scientific disclosure at
upcoming congresses and in peer reviewed publications. 

DOSING IN GRIPHON

Uptitration  of  selexipag  allows  each  patient's  maintenance  dose  to  be 
individualized based on tolerability. Dosing  in GRIPHON was initiated at  200 
micrograms (mcg) bid and  increased in steps  of 200 mcg twice  daily up to  a 
maximum of 1600 mcg twice daily.

ABOUT THE SAFETY AND TOLERABILITY IN GRIPHON

The most common adverse events in GRIPHON that occurred with higher  frequency 
on selexipag  than  placebo were  in-line  with those  known  in  prostacyclin 
therapies; headache, diarrhea, nausea, jaw pain, vomiting, pain in  extremity, 
myalgia, nasopharyngitis and flushing.

The proportion of patients discontinuing  treatment due to adverse events  was 
14 percent on selexipag and 7 percent on placebo.

ABOUT GRIPHON

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

The GRIPHON  study  was the  largest  outcome  trial ever  conducted  in  PAH, 
enrolling patients  in  181 centers  from  39  countries in  North  and  Latin 
America, Europe, Asia-Pacific and Africa.

GRIPHON  enrollment  was  completed  in  May  2013  with  1'156  patients  and 
represents the largest randomized, controlled study in PAH patients.  Patients 
received twice  daily administration  of selexipag  or placebo  and were  also 
permitted to  receive background  therapy  of endothelin  receptor  antagonist 
and/or a phosphodiesterase-5 inhibitor  when on a stable  dose for at least  3 
months prior to enrollment. At baseline,  80% of patients were receiving  oral 
medication  specific  for  PAH:  either  an  ERA,  a  PDE-5  inhibitor,  or  a 
combination of the two.

This pivotal, event-driven study was designed to demonstrate a prolongation of
time to the first morbidity/mortality event for selexipag compared to  placebo 
and to evaluate the safety of the selexipag in PAH patients. All morbidity and
mortality  events  reported  by  the  investigators  were  adjudicated  by  an 
independent Critical Event Committee blinded to the study treatment.

ABOUT SELEXIPAG

Selexipag, originally  discovered and  synthesized by  Nippon Shinyaku,  is  a 
potent, orally available, selective prostacyclin IP receptor agonist.

Selexipag  selectively  targets   the  prostacyclin   receptor  (also   called 
IP-receptor). The  IP receptor  is  one of  5  types of  prostanoid  receptor. 
Prostacyclin activates the  IP receptor inducing  vasodilation and  inhibiting 
proliferation of vascular smooth muscle cells. Selexipag, unlike  prostacyclin 
analogs, is selective for the IP receptor over other prostanoid receptors.  In 
preclinical models  selective  IP  receptor  agonism  has  shown  to  maintain 
efficacy and reduce the risk of  side effects mediated by activation of  other 
prostanoid receptors, such as EP[1] and EP[3] receptors. [2,4,5]

Selexipag   was   previously   evaluated   in   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 PDE-5 inhibitor and/or  ERA 
[6]



                                     ###



Notes to Editor:

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 three  pathways 
that have been established in the pathogenesis of PAH are endothelin  receptor 
antagonists (ERAs), prostacyclin  analogs 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.

In PAH, survival rates are unacceptably low and PAH remains incurable.

ABOUT PROSTACYCLIN

Prostacyclin is a prostanoid and serves  as a signaling molecule in the  human 
body. It is produced, like other vasoactive substances, by endothelial  cells. 
Prostacyclin    induces    vasodilation,     is    anti-proliferative,     has 
anti-inflammatory  effects  and  inhibits  platelet  aggregation.  In  certain 
disease conditions,  the  production of  prostacyclin  by the  endothelium  is 
impaired, allowing for example the deleterious effects of excessive levels  of 
endothelin to predominate.

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 orally-available,  selective 
prostacyclin  IP  receptor  agonist  for  patients  suffering  from  pulmonary 
arterial hypertension  (PAH).  This  compound was  originally  discovered  and 
synthesized by Nippon Shinyaku. 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.Mubarak KK. A review of prostaglandin analogs in the management of
    patients with pulmonary arterial hypertension. Respir Med 2010;104:9-21.
4.Morrison et al. Selexipag: a selective prostacyclin receptor agonist that
    does not affect rat gastric function. J Pharmacol Exp Ther
    2010;335:249-255.
5.Morrison et al. Differential effects of selexipag and prostacyclin analogs
    in rat pulmonary artery. J Pharmacol Exp Ther 2012;343:547-555.
6.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

Dr. McLaughlin is a consultant to Actelion



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 leading biopharmaceutical company focused on the discovery,
development and  commercialization  of  innovative  drugs  for  diseases  with 
significant unmet medical needs.

Actelion is a leader  in the field of  pulmonary arterial hypertension  (PAH). 
Our portfolio  of PAH  treatments covers  the spectrum  of disease,  from  WHO 
Functional Class (FC) II through to FC IV, with oral, inhaled and  intravenous 
medications. Although not available in all countries, Actelion has  treatments 
approved by health authorities for  a number of specialist diseases  including 
Type 1  Gaucher  disease,  Niemann-Pick  type C  disease,  Digital  Ulcers  in 
patients  suffering  from  systemic  sclerosis,  and  mycosis  fungoides  type 
cutaneous T-cell lymphoma.

Founded in late 1997, with now over 2,400 dedicated professionals covering all
key markets around the  world including Europe, the  US, Japan, China,  Russia 
and Mexico,  Actelion has  its corporate  headquarters in  Allschwil /  Basel, 
Switzerland.

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®).  All 
trademarks are legally protected.



For further information please contact:

Andrew Weiss
Senior Vice President, Head of Investor Relations & Corporate Communications
Actelion Pharmaceuticals Ltd, Gewerbestrasse 16, CH-4123 Allschwil
+41 61 565 62 62
http://www.actelion.com



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herein as anticipated, believed, estimated or expected.

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Gewerbestrasse 16 Allschwil Switzerland

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