Actelion receives Therapeutic Goods Administration (TGA) approval in Australia for Opsumit (macitentan) in Pulmonary Arterial Hypertension (PAH)
Actelion Pharmaceuticals Ltd /
Actelion receives Therapeutic Goods Administration (TGA) approval in Australia
for Opsumit (macitentan) in Pulmonary Arterial Hypertension (PAH)
. Processed and transmitted by NASDAQ OMX Corporate Solutions.
The issuer is solely responsible for the content of this announcement.
ALLSCHWIL/BASEL, SWITZERLAND - 07 February 2014 - Actelion Ltd (SIX: ATLN) today
announced the approval of OpsumitÂ® (macitentan) 10 mg for the treatment of
pulmonary arterial hypertension (PAH) by the Therapeutic Goods Administration
(TGA) of Australia.
Opsumit, as monotherapy or in combination with approved PAH treatments
(phosphodiesterase-5 inhibitors or inhaled prostanoids), is indicated for the
treatment of idiopathic and heritable PAH as well as PAH associated with
connective tissue disease and PAH associated with congenital heart disease with
repaired shunts in patients with WHO Functional class II,III or IV symptoms.
Professor Trevor Williams, Clinical Director of the Department of Allergy,
Immunology and Respiratory Medicine at Alfred Hospital and Monash University,
Melbourne, Australia commented, "The approval of Opsumit is a key milestone in
the management of PAH. We now have confidence that we can improve long term
clinical outcomes both in treatment naÃ¯ve patients and those on combination
therapy. Hopefully all new pulmonary arterial hypertension drugs will be
subjected to such extensive level of rigorous clinical evaluation and
demonstrate clinically important results."
The TGA's approval was based on data from the landmark Phase III SERAPHIN study.
In the SERAPHIN study, treatment with macitentan 10 mg resulted in a 45% risk
reduction (hazard ratio [HR] 0.55; 97.5% CI: 0.39 to 0.76; logrank p < 0.0001)
of the composite morbidity-mortality endpoint when compared to placebo.
Jean-Paul Clozel, M.D. and Chief Executive Officer of Actelion gave his reaction
to the news: "This approval marks a significant moment for the PAH community in
Australia as Opsumit is the first and only PAH treatment with proven long-term
efficacy in controlled clinical trials in PAH, and will now offer hope of a
better future to those living with this disease. Actelion is now working to make
this important medicine available to patients around Australia in the coming
The most common adverse events that were reported at a frequency at least 3%
greater on macitentan than on placebo were nasopharyngitis (14.0% macitentan vs
10.4% placebo), headache (13.6% vs 8.8%) and anaemia (13.2% vs 3.2%)
Opsumit was approved by the US FDA in October 2013, Health Canada in November
2013 and by the EU Commission in December 2013. It is also undergoing regulatory
assessment in other countries including Switzerland.
NOTES TO THE EDITOR
ABOUT OPSUMIT(Â®) (MACITENTAN)
Opsumit (macitentan) is a novel dual endothelin receptor antagonist (ERA) that
resulted from a tailored drug discovery process with the target of developing an
ERA to address efficacy and safety [2,3].
ABOUT THE SERAPHIN STUDY
SERAPHIN (Study with an Endothelin Receptor Antagonist in Pulmonary arterial
Hypertension to Improve cliNical outcome) was the largest and longest
randomized, controlled study in PAH patients to include a clearly defined
morbidity/mortality primary endpoint . The pivotal Phase III study was
designed to evaluate the efficacy and safety of Opsumit (macitentan) - a novel
dual endothelin receptor antagonist that resulted from a tailored drug discovery
process - through the primary endpoint of time to first morbidity and all-cause
mortality event in patients with symptomatic PAH.
Global enrolment was completed in December 2009 with a total of 742 patients.
Patients were randomized 1:1:1 to receive two different doses of macitentan (3
mg and 10 mg once daily) or placebo. Patients were allowed to receive PAH
background therapy throughout the study, either PDE-5 inhibitors or oral/inhaled
prostanoids. This event-driven study was conducted in 151 centers from almost
40 countries in North America, Latin America, Europe, Asia-Pacific and Africa
and was completed in the first half of 2012, with 287 patients having an
ABOUT SERAPHIN STUDY DATA
Patients were randomized to placebo (n=250), macitentan 3 mg (n=250), or
macitentan 10 mg (n=242). The primary end point occurred in 46.4%, 38.0%, and
31.4% of the patients in these groups, respectively. The hazard ratio for
macitentan 3 mg versus placebo was 0.70 (97.5% CI, 0.52 to 0.96; p=0.0108) and
the hazard ratio for macitentan 10 mg versus placebo was 0.55 (97.5% CI, 0.39 to
0.76; p<0.0001). Worsening of pulmonary arterial hypertension was the most
frequent primary end point event. The effect of macitentan on this end point was
observed irrespective of background therapy for pulmonary arterial hypertension.
ABOUT THE SAFETY AND TOLERABILITY PROFILE
The most commonly reported adverse drug reactions with Opsumit are
nasopharyngitis (14.0%), headache (13.6%) and anaemia (13.2%).
ABOUT OPSUMIT (MACITENTAN) SUBMISSIONS TO HEALTHCARE AUTHORITIES
The first approval globally of the new drug application for Opsumit (macitentan)
was issued by the US Food and Drug Administration (FDA) on 18 October 2013 for
the treatment of pulmonary arterial hypertension (PAH, WHO Group I) to delay
disease progression. Disease progression included: death, initiation of
intravenous (IV) or subcutaneous prostanoids, or clinical worsening of PAH
(decreased 6-minute walk distance, worsened PAH symptoms and need for additional
PAH treatment). Opsumit also reduced hospitalization for PAH.
Regulatory reviews are ongoing in Switzerland, Taiwan, Mexico, Korea and Israel.
ABOUT PULMONARY ARTERIAL HYPERTENSION [4, 5, 6]
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), prostacyclins 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.
1. Pulido TÂ et al.Â Macitentan and Morbidity and Mortality in Pulmonary Arterial
Hypertension.Â NÂ Engl J MedÂ 2013;369:809-18.
2. Bolli MH et al. The Discovery of N-[5-(4-Bromophenyl)-6-[2-[(5-bromo-2-
pyrimidinyl)oxy]ethoxy]-4-pyrimidinyl]-N'-propylsulfamide (Macitentan), an
Orally Active, Potent Dual Endothelin Receptor Antagonist. J Med Chem.
3. Iglarz M. et al. Pharmacology of macitentan, an orally active tissue
targeting dual endothelin receptor antagonist. J Pharmacol Exp Ther.
4. Proceedings of the 4th world symposium on pulmonary hypertension. J Am
CollCardiol 2009;54(1 Suppl).
5. GaliÃ¨ N, Hoeper MM, Humbert M, et al; ESC Committee for Practice Guidelines
(CPG). Guidelines for the diagnosis and treatment of pulmonary hypertension:
the Task Force for the Diagnosis and Treatment of Pulmonary Hypertension of
the European Society of Cardiology (ESC) and the European Respiratory
Society (ERS), endorsed by the International Society of Heart and Lung
Transplantation (ISHLT). Eur Heart J 2009;30:2493-537.
6. Benza RL, Miller DP, Barst RJ, Badesch DB, Frost AE, McGoon MD. An
evaluation of long-term survival from time of diagnosis in pulmonary
arterial hypertension from REVEAL. Chest 2012;142:448-56.
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 in patients with cutaneous T-cell
Founded in late 1997, with now over 2,400 dedicated professionals covering all
key markets around the world including 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 SMIÂ®). All trademarks
are legally protected.
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
The above information contains certain "forward-looking statements", relating to
the company's business, which can be identified by the use of forward-looking
terminology such as "estimates",Â "believes", "expects", "may", "are expected
to", "will", "will continue", "should", "would be", "seeks",Â "pending" or
"anticipates" or similar expressions, or by discussions of strategy, plans or
intentions.Â Such statements include descriptions of the company's investment
and research and development programs and anticipated expenditures in connection
therewith, descriptions of new products expected to be introduced by the company
and anticipated customer demand for such products and products in the company's
existing portfolio. Such statements reflect the current views of the company
with respect to future events and are subject to certain risks, uncertainties
and assumptions. Many factors could cause the actual results, performance or
achievements of the company to be materially different from any future results,
performances or achievements that may be expressed or implied by such forward-
looking statements. Should one or more of 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.
Press Release PDF:
This announcement is distributed by GlobeNewswire on behalf of
GlobeNewswire clients. The owner of this announcement warrants that:
(i) the releases contained herein are protected by copyright and
other applicable laws; and
(ii) they are solely responsible for the content, accuracy and
originality of the information contained therein.
Source: Actelion Pharmaceuticals Ltd via GlobeNewswire