LAVAL, QC, Nov. 12, 2013 /CNW/ - Actelion Pharmaceuticals Canada Inc.
announced today that Health Canada has approved the oral endothelin
receptor antagonist OPSUMIT (macitentan) 10mg once daily for the long term treatment of pulmonary
arterial hypertension (PAH) to reduce morbidity.
OPSUMIT is indicated for the long-term treatment of pulmonary arterial
hypertension (PAH, WHO Group1) to reduce morbidity in patients in WHO
Functional Class II or III whose PAH is either idiopathic or heritable,
or associated with connective tissue disease or congenital heart
disease. OPSUMIT is effective when used as monotherapy or in
combination with phosphodiesterase-5 inhibitors.
The safety and efficacy of OPSUMIT were evaluated in the largest and
longest randomized, placebo-controlled study in PAH patients, called
SERAPHIN (Study with Endothelin Receptor Antagonist in Pulmonary Arterial Hypertension to Improve Clinical Outcome). 
Approval by Health Canada was based in part on data from this landmark
phase III study published in the New England Journal of Medicine in
August 2013. It was the first long-term study to include a clearly
defined, clinically-important morbidity/mortality primary endpoint.
Effectiveness was established in PAH patients with predominantly WHO
Functional Class II-III symptoms treated for an average of 2 years with
OPSUMIT monotherapy or in combination with phosphodiesterase-5
inhibitors (61%). The primary study endpoint was the time to first
occurrence of a morbidity or mortality event up to end of double-blind
treatment (EOT). 
"This new study represents a critical milestone in the treatment of PAH
patients. We now have a new standard of excellence for clinical trials
in PAH, and the strongest evidence ever of hope for long-term improved
quality of life and clinical stability for those affected by PAH in
Canada," said Dr. Sanjay Mehta, MD, FRCPC, FCCP, Professor of Medicine
at Western University, Director of the Southwest Ontario Pulmonary
Hypertension Clinic at the London Health Sciences Center in London,
Ontario and Chair of the Pulmonary Hypertension Association of Canada.
"Five years ago, global and Canadian experts in PAH proposed that future
PAH clinical studies should assess the effects of treatment on
long-term morbidity and mortality, a clinically more important primary
endpoint compared to all previous studies which only looked at very
short-term outcomes, such as the six minute walk test. Today, thanks to
OPSUMIT, we now have an answer to this critical question of long-term
benefits of PAH treatment on clinical outcomes important to patients,"
continued Dr. Mehta who was also a SERAPHIN investigator and co-author
of the published article in the New England Journal of Medicine.
"This approval marks a significant turning point in the management of
PAH in Canada," said Jacques Archambault, President of Actelion
Pharmaceuticals Canada Inc. "We look forward to continuing our work to
improve the standard of care for Canadians living with PAH."
The SERAPHIN study showed that the risk of the first occurrence of a
morbidity or mortality event, the primary endpoint of the study, was
reduced by 45% (p<0.0001) with macitentan 10 mg daily compared to
placebo. This effect was observed irrespective of whether or not
patients were already treated with other therapies for PAH. SERAPHIN
also showed a risk reduction in PAH related hospitalization and death
of 50% (p<0.0001) compared to placebo. 
"Canadians living with PAH are not only in a constant battle with
devastating symptoms that can drastically impact their daily life, they
also face the very real possibility of a shortened lifespan - and even
death," said Ruth Dolan, director of the Pulmonary Hypertension
Association of Canada, and mother of a PAH patient. "Patients need
better PAH treatment options proven to reduce hospitalizations and
death due to their disease."
OPSUMIT is a novel dual endothelin receptor antagonist (ERA) that
resulted from a tailored drug discovery process that focused on
developing an ERA that was optimized for efficacy and safety.  The
clinical pharmacology program also indicated a low propensity of
OPSUMIT for drug-drug interactions. [3,4,5]
OPSUMIT is contraindicated in patients who are hypersensitive to this
drug or to any ingredient in the formulation or component of the
container; women who are or may become pregnant and nursing women (see
Warnings and Precautions, Special Populations, Pregnant and Nursing
Women sections of the product monograph).
The most common adverse reactions (more frequent than placebo by 3% or
more) observed in patients treated with OPSUMIT were anemia,
nasopharyngitis/pharyngitis, bronchitis, headache, influenza, and
urinary tract infection.
Physicians are advised to measure hemoglobin prior to initiation of
treatment, again after one month, and periodically thereafter as
clinically indicated. Liver enzyme blood tests should be obtained prior
to initiation of OPSUMIT, and monthly testing during the first year of
treatment is recommended and then less frequently thereafter as
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.
About Actelion Ltd
Actelion Ltd is a biopharmaceutical company with its corporate
headquarters in Allschwil/Basel, Switzerland. Actelion's first drug
Tracleer® (bosentan), 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®).
To learn more about Actelion Pharmaceuticals, visit www.actelion.com.
About OPSUMIT® (macitentan) submissions to healthcare authorities
OPSUMIT® was recently approved in the United States. Actelion expects
OPSUMIT to become available to patients in early 2014 in Canada.
Outside of Canada, Actelion continues to work with health authorities
to obtain regulatory approval for OPSUMIT.
OPSUMIT® is a registered trademark in the US and other countries.
Pulido T, Adzerikho I, Channick RN, Delcroix M, Galiè N, Ghofrani H-A,
et al. Macitentan and Morbidity and Mortality in Pulmonary Arterial
Hypertension. N Engl J Med. 2013;369(9):809-818.
Bolli MH et al. The Discovery of
(Macitentan), an Orally Active, Potent Dual Endothelin Receptor
Antagonist. J Med Chem. 2012; 55:7849-61.
Sidharta PN et al. Macitentan: Entry-into-humans study with a new
endothelin receptor antagonist. Eur J Clin Pharmacol.
Bruderer S et al. Absorption, distribution, metabolism, and excretion of
macitentan, a dual endothelin receptor antagonist, in humans.
Xenobiotica. 2012 Sep;42(9):901-10
Bruderer S et al. Effect of cyclosporine A and rifampin on the
pharmacokinetics of macitentan, a tissue-targeting dual endothelin
receptor antagonist. AAPS J. 2012;14(1):68-78.
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SOURCE: Actelion Pharmaceuticals Canada Inc.
For further information:
Cohn & Wolfe
Director, Medical Affairs
Actelion Pharmaceuticals Canada Inc.
Laval, QC, Canada