Actelion Pharmaceuticals Ltd : Actelion's novel antibiotic cadazolid to move into Phase III clinical development in patients

 Actelion Pharmaceuticals Ltd : Actelion's novel antibiotic cadazolid to move
  into Phase III clinical development in patients suffering from Clostridium
                        difficile associated diarrhea

Actelion Pharmaceuticals Ltd / Actelion's novel antibiotic cadazolid to move
into Phase III clinical development in patients suffering from Clostridium
difficile associated diarrhea . Processed and transmitted by Thomson Reuters
ONE. The issuer is solely responsible for the content of this announcement.

ALLSCHWIL/BASEL, SWITZERLAND  -  21  December  2012  -  Actelion  (SIX:  ATLN) 
announced today that it  has decided to move  forward with Phase III  clinical 
development of  cadazolid in  patients  suffering from  Clostridium  difficile 
associated diarrhea (CDAD).

The decision is  based on the  results of a  therapeutic exploratory Phase  II 
dose-finding study randomizing 84 patients. The study evaluated the  efficacy, 
safety  and  tolerability  of  3  doses  of  cadazolid  (administered  orally, 
twice-daily) versus vancomycin, as an  active reference, (125 mg  administered 
orally, four times daily) for 10 days. The study, with a limited sample  size, 
was not designed to compare statistically cadazolid versus vancomycin.

The results of this Phase  II study indicate that the  effect of all doses  of 
cadazolid are  numerically  similar  to,  or better  than  vancomycin  on  key 
endpoints including CDAD cure rates as well as sustained cure rates. Cure rate
was defined as the resolution of diarrhea and no further need for CDAD therapy
at test-of-cure  24  to 72  hours  after the  last  dose of  treatment,  while 
sustained cure rate was defined as cured with no recurrence of diarrhea up  to 
4 weeks post-treatment.

Recurrence rates were numerically lower for all doses of cadazolid as compared
to vancomycin. Recurrence rate was defined as a new episode of diarrhea and  a 
positive Clostridium difficile toxin test.

Guy Braunstein, M.D. and Head of Clinical Development commented: "This is  the 
first time  cadazolid  has  been  used  to  treat  patients,  delivering  very 
encouraging clinical  data with  this new  class of  antibiotics. The  results 
provide clear  information  to  support  further evaluation  in  a  Phase  III 
program. Results of microbiology and pharmacokinetic assessments will soon  be 
available allowing us to further characterize cadazolid."

Cadazolid was safe and well tolerated, at present no safety signals have  been 
identified.
Once full data analysis of  this exploratory dose-finding study for  cadazolid 
has been completed, Actelion will discuss  the details of a Phase III  program 
with Health  Authorities. Actelion  will  present the  results of  this  study 
through scientific presentations and publications.

Jean-Paul Clozel, M.D. and Chief  Executive Officer commented: "This year  we, 
at Actelion,  made  significant  progress  to deliver  on  our  strategy.  The 
landmark results for macitentan (Opsumit®) will  allow us to sustain and  grow 
our pulmonary arterial hypertension business. Now, with the results from  both 
ponesimod in psoriasis and cadazolid in CDAD, we have laid the foundation  for 
our mid-term goal of building a second specialty franchise."

                                     ###

Notes to the Editor

About cadazolid in Clostridium difficile associated diarrhea

Cadazolid was  studied in  a  multi-center, double-blind,  randomized,  active 
reference, parallel  group, therapeutic  exploratory dose-finding  study.  The 
study evaluated the efficacy, safety and tolerability of a 10-day, twice daily
oral administration  of  3 doses  (250  mg, 500  mg  or 1,000  mg  b.i.d.)  of 
cadazolid in patients with  Clostridium difficile associated diarrhea  (CDAD). 
As the current standard of care for  CDAD, oral vancomycin (125 mg qid for  10 
days) was used as the active reference. The study was completed in December of
2012, after having enrolled 84 patients.

About the efficacy measurements used in the study

In CDAD, as in  most acute infectious diseases,  the clinically most  relevant 
parameter for assessing  treatment efficacy in  a Phase II  study is  clinical 
response at  the  end of  therapy  (in  this case  principally  resolution  of 
diarrhea), which was evaluated at the Test-of-Cure visit (24 to 72 hours after
the last dose  of study  treatment). In current  and past  clinical trials  in 
CDAD, clinical cure rate is consistently selected as the primary endpoint.

In CDAD, disease recurrence is  an additional important parameter.  Recurrence 
during the 4 weeks after the end of treatment is chosen as the main  secondary 
endpoint.

About cadazolid

Cadazolid, a  quinolonyl-oxazolidinone  is  a  new  chimeric  antibiotic  with 
structural elements of  the oxazolidinone as  well as the  quinolone class  of 
antibiotics. It  is a  strong  inhibitor of  Clostridium difficile  (C.  diff) 
protein synthesis leading to strong suppression of toxin and spore  formation. 
In preclinical studies cadazolid  showed potent in  vitro activity against  C. 
diff clinical  isolates and  in a  human gut  model of  Clostridium  difficile 
associated diarrhea  (CDAD),  while  having  only a  very  limited  impact  on 
bacteria of the normal gut  microflora. In addition, cadazolid demonstrated  a 
low propensity for resistance development.

Cadazolid absorption is negligible resulting in high gut lumen  concentrations 
and low systemic exposure, even in severe cases of CDAD where the gut wall can
be severely  damaged  and permeability  to  drugs potentially  increased.  The 
observed  preclinical  and  clinical  pharmacology  and  safety  profiles   of 
cadazolid supported further clinical development in CDAD.

About Clostridium difficile associated diarrhea

Clostridium difficile(C. diff)  is a  Gram-positive, anaerobic,  spore-forming 
bacterium that  is  the  leading cause  of  nosocomial  diarrhea.  Clostridium 
difficile associated diarrhea  (CDAD or CDI  for C. diff  infection) can be  a 
severe and life-threatening  disease and  results from the  overgrowth in  the 
colon of toxigenic strains of C. diff, generally during or after therapy  with 
broad-spectrum antibiotics. CDAD is a  major healthcare problem and a  leading 
cause of  morbidity  in  elderly  hospitalized  patients.  The  frequency  and 
severity of CDAD in the western world  has increased in recent years, and  new 
hypervirulent and epidemic strains  of C. diff have  been discovered that  are 
characterized by overproduction of toxins and other virulence factors, and  by 
acquired resistance to fluoroquinolones such as moxifloxacin.

Current antibiotic  therapy for  CDAD includes  vancomycin and  metronidazole. 
While cure  rates are  generally 85-90%,  recurrences rates  of 15-30  %  with 
either drug are  problematic C.  diff produces  spores that  are resistant  to 
antibiotic treatment and routine disinfection. Spores surviving in the gut  of 
patients and/or  in  the  hospital  environment  may  play  a  major  role  in 
re-infection and relapse  of CDAD after  antibiotic treatment, Vancomycin  and 
metronidazole  are  reported   to  promote   spore  formation   in  vitro   at 
sub-inhibitory concentrations.

Only one new antibiotic, fidaxomicin, has been approved over the last 30 years
for this indication,  and there  remains a need  for new  drugs with  improved 
properties. In  particular,  antibiotics  that allow  effective  treatment  of 
infections caused by hypervirulent strains with low recurrence rates.

Reference

1.D. Baldoni,et al,Cadazolid,  a novel quinolonyl-oxazolidinone  antibiotic 
    with potent activity  againstClostridium difficile: safety,  tolerability, 
    and pharmacokinetics  in healthy  subjects following  single and  multiple 
    oral doses.Poster (A-1273)presentedat  theInterscience Conference  on 
    Antimicrobial Agents  and Chemotherapy  (ICAAC), 9-12  Septmber 2012,  San 
    Francisco.

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
www.actelion.com

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herein as anticipated, believed, estimated or expected.

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Actelion Pharmaceuticals Ltd
Gewerbestrasse 16 Allschwil Switzerland

ISIN: CH0010532478;
 
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