Actelion Pharmaceuticals Ltd : Actelion's ponesimod successful in mid-stage trial in patients with moderate to severe chronic

 Actelion Pharmaceuticals Ltd : Actelion's ponesimod successful in mid-stage
trial in patients with moderate to severe chronic plaque psoriasis - Ponesimod
          to proceed to Phase III clinical development in psoriasis

Actelion Pharmaceuticals Ltd / Actelion's ponesimod successful in mid-stage
trial in patients with moderate to severe chronic plaque psoriasis - Ponesimod
to proceed to Phase III clinical development in psoriasis . Processed and
transmitted by Thomson Reuters ONE. The issuer is solely responsible for the
content of this announcement.

ALLSCHWIL/BASEL, SWITZERLAND  -  18  December  2012  -  Actelion  (SIX:  ATLN) 
announced today that its  selective S1P[1] modulator, ponesimod,  successfully 
met the  primary endpoint  - the  proportion  of patients  with at  least  75% 
improvement in Psoriasis Area and Severity Index (PASI) from baseline (PASI75)
at week 16  - in  a double blind,  placebo-controlled study  conducted in  326 
patients with moderate to severe chronic plaque psoriasis.

Results of the  primary endpoint  were highly  statistically significant  with 
both tested doses. With Ponesimod 20 mg, 46 % of patients improved by at least
75 % at  week 16 (p<0.0001  versus placebo).  With Ponesimod 40  mg, 48.1%  of 
patients improved by at least  75 % at week  16 (p<0.0001 versus placebo).  An 
improvement by at least 75 % was observed  at week 16 in 13.4% of the  placebo 
treated patients. Both doses were administered once daily.

At the end of induction, ponesimod patients improving at least 50% or more  in 
their PASI score at week 16  were re-randomized to either continuation of  the 
same dose of ponesimod, or to placebo.

After the initial 16  week induction phase of  the study, further  improvement 
was seen with  ponesimod during the  12-week double-blind,  placebo-controlled 
maintenance period. Among patients continuing  on ponesimod 20 and 40mg,  71% 
and 77 % achieved PASI75 at the end of the study, respectively.

Efficacy was also demonstrated across other endpoints of the study,  including 
Physician Global Assessment (PGA) at week 16.

Guy Braunstein, M.D. and Head  of Clinical Development at Actelion  commented: 
"This is the  first time that  this mechanism has  demonstrated efficacy  with 
psoriasis patients. Analysis during the maintenance period of the study showed
patients continued  to improve  beyond the  initial 16  week induction  phase. 
Having conducted such a large Phase II  study we have the information we  need 
for the design of the pivotal Phase III program."

Safety and tolerability  data from the  study are consistent  with the  safety 
profile of  ponesimod observed  in previous  studies conducted  including  the 
Phase II study with multiple sclerosis patients.[3] At initiation of ponesimod
treatment, transient reductions in heart rate and less frequently, a transient
effect on atrioventricular conduction were observed in the study as  expected. 
The  most  frequent   adverse  events   (AEs)  reported   for  ponesimod   was 
dose-dependent dyspnea  and  asymptomatic liver  enzyme  elevations.  Overall, 
there were no indications of an increased infection rate with ponesimod in the
study with the exposure to ponesimod up to 28 weeks. The safety data-base from
all studies with ponesimod, now comprises more than 1,100 patients and healthy
volunteers with some patients treated for up to 3.3 years.

Jean-Paul Clozel, M.D. and Chief Executive Officer commented: "We are  excited 
to now know that ponesimod, originating from Actelion's discovery effort,  has 
the potential  to  become an  important  treatment option  in  immune-mediated 
disorders in  addition  to  multiple sclerosis.  Actelion  will  rapidly  move 
forward with  the preparation  of  the pivotal  program and  discussions  with 
health authorities for the psoriasis indication."

Once full data analysis has been concluded, Actelion will discuss the  details 
of the  upcoming Phase  III  program with  health authorities.  Actelion  will 
present  the   results  of   this   dose-finding  study   through   scientific 
presentations and publications.


Notes to the Editor

About ponesimod in psoriasis

Ponesimod was  studied  in patients  with  moderate-to-severe psoriasis  in  a 
multicenter,  randomized,  double-blind,  placebo-controlled,   parallel-group 
trial that evaluated the efficacy, safety and tolerability of 2 dose levels of
ponesimod administered during 16 weeks. This induction period was followed  by 
a 12-week maintenance period during which patients treated with ponesimod  and 
reaching PASI50 at week 16 were treated either with ponesimod or placebo,  for 
a total of up to 28 weeks.  This 326-patient study started enrollment in  2010 
and was completed in November of 2012.

About the efficacy measurements used in the study

Efficacy of a potential therapy for  psoriasis is commonly measured using  the 
Psoriasis Area and Severity Index (PASI). A reduction of at least 75% in  PASI 
from baseline is typically  considered clinically meaningful  by the CHMP  and 
clinicians [EMEA 2004]. The CHMP [EMEA 2004] recommends using two endpoints to
assess efficacy: PASI  in conjunction  with a  validated, standardized  global 
score  such  as  Physician's  Global  Assessment  (PGA).  In  this  mid  stage 
dose-finding study PASI has been chosen  as the primary efficacy endpoint  and 
PGA as the secondary endpoint.

About Psoriasis

Psoriasis is  a  chronic,  relapsing, inflammatory  and  immune-mediated  skin 
disease affecting about 1-3% of the population worldwide. Plaque psoriasis  is 
the most  common form  of psoriasis,  constituting ~  85% of  cases. The  most 
characteristic skin lesions of chronic plaque psoriasis are sharply demarcated
erythematous plaques, covered  by silvery  white scales,  which most  commonly 
occur on  the elbows,  knees,  scalp, umbilicus,  and lumbar  area.  Children, 
adolescents, and adults are affected.

About the Phase IIb study with ponesimod in multiple sclerosis [1,2,3]

A Phase  IIb  dose-finding study  with  ponesimod in  multiple  sclerosis  was 
successfully completed in July 2011.  The study assessed efficacy, safety  and 
tolerability of three ponesimod  dose levels (10  mg, 20 mg  or 40 mg)  versus 
placebo, administered orally once daily for 24 weeks with 464 patients.

In this study, ponesimod  significantly reduced the  cumulative number of  new 
active lesions  on  monthly  magnetic  resonance  imaging  (MRI)  brain  scans 
performed from weeks 12  to 24. As compared  to placebo, the primary  endpoint 
was reduced by 43% (p<0.05), 83% (p<0.0001) and 77% (p<0.0001) with  ponesimod 
10, 20 and 40 mg, respectively.

Ponesimod exhibited an adverse event pattern in this study that, if  confirmed 
in a  Phase  III  program,  would give  ponesimod  a  competitive  safety  and 
tolerability profile.

About S1P receptors

Sphingosine-1-phosphate (S1P)  is  a sphingolipid  released  by  erythrocytes, 
platelets, mast cells and other cell  types. It is currently established  that 
S1P stimulates at least five different cell surface resident G-protein coupled
receptors (GPCRs) - S1P[1,2,3,4,] and [5]. Activation of these GPCRs  mediates 
a complex  variety  of  biological responses  such  as  lymphocyte  migration, 
endothelial cell  proliferation,  blood  vessel constriction  and  heart  rate 

About the selective S1P[1] immunomodulator ponesimod

Ponesimod is an  orally active, selective  sphingosine 1-phosphate receptor  1 
(S1P[1]) immunomodulator. Ponesimod  prevents lymphocytes  from leaving  lymph 
nodes, thereby  reducing circulating  blood lymphocyte  counts and  preventing 
infiltration  of  lymphocytes  into  target  tissues.  The  lymphocyte   count 
reduction is rapid,  dose-responsive, is sustained  with continued dosing  and 
quickly   reversed   upon   discontinuation.   Ponesimod   does   not    cause 
lymphotoxicity: it  does  not  destroy lymphocytes  or  interfere  with  their 
cellular function. Other blood  cells e.g. cells of  the innate immune  system 
are unaffected  and remain  available  to fight  off infection.  Ponesimod  is 
therefore considered a promising new oral agent for the treatment of a variety
of autoimmune disorders.

About Actelion and selective S1P[1] immunomodulators

Actelion's efforts in the field of selective S1P[1] receptor  immunomodulators 
started in  1999 by  focusing on  GPCRs found  on the  endothelium, the  inner 
lining of blood vessels.  The result of these  research efforts is  Actelion's 
orally active selective S1P[1] receptor agonist, ponesimod.


1. Olsson  T, et  al; Efficacy  and safety  of ponesimod,  an oral,  selective 
sphingosine   1-phosphate    receptor-1    modulator,   in    patients    with 
relapsing-remitting multiple sclerosis: Results from a phase IIb,  randomised, 
double-blind, placebo-controlled trial. Multiple  Sclerosis Journal, 2012;  18 
(4 suppl): 49 (152).

2. Freedman M.S, et al; Dose-dependent effect of ponesimod, an oral, selective
sphingosine 1-phosphate receptor-1  modulator, on  magnetic resonance  imaging 
outcomes in  patients with  relapsing-remitting multiple  sclerosis.  Multiple 
Sclerosis Journal, 2012; 18 (4 suppl): 420 (P923).

3. Fernández  Ó, et  al; Pharmacodynamic  effect, safety  and tolerability  of 
ponesimod,  a  selective  sphingosine  1-phosphate  receptor-1  modulator,  in 
patients  with  relapsing-remitting  multiple  sclerosis.  Multiple  Sclerosis 
Journal, 2012; 18 (4 suppl): 417 (P919).

4. Bolli  MH et  al; 2010;  2-imino-thiazolidin-4-one derivatives  as  potent, 
orally active S1P1 receptor agonists. J Med Chem 53:4198-4211.

5. Matloubian M  et al;  2004; Lymphocyte  egress from  thymus and  peripheral 
lymphoid organs is dependent on S1P receptor 1. Nature 427:355-360.

6. Piali  L et  al; 2011;  The selective  sphingosine 1-phosphate  receptor  1 
agonist ponesimod protects against lymphocyte-mediated tissue inflammation.  J 
Pharmacol Exp Ther 337:547-556.

7. Rosen H and Goetzl EJ; 2005; Sphingosine 1-phosphate and its receptors:  an 
autocrine and paracrine network. Nat Rev Immunol 5:560-570.

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 2,400  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
Senior 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

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actual results, performance or  achievements of the  company to be  materially 
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these risks  or uncertainties  materialize, or  should underlying  assumptions 
prove incorrect,  actual  results may  vary  materially from  those  described 
herein as anticipated, believed, estimated or expected.

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Actelion Pharmaceuticals Ltd
Gewerbestrasse 16 Allschwil Switzerland

ISIN: CH0010532478;
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