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
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
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
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.
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
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:
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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