Actelion is granted marketing authorization for Uptravi (selexipag) in pulmonary arterial hypertension by the European Commission
(Thomson Reuters ONE) -
Actelion Pharmaceuticals Ltd /
Actelion is granted marketing authorization for Uptravi (selexipag) in pulmonary
arterial hypertension by the European Commission
. Processed and transmitted by NASDAQ OMX Corporate Solutions.
The issuer is solely responsible for the content of this announcement.
* Marketing authorization granted by European Commission on 12 May 2016
* First European Union (EU) market introduction to commence in the near future
ALLSCHWIL, SWITZERLAND - 17 May 2016 - Actelion (SIX: ATLN) announced today
that the European Commission has granted marketing authorization in the EU for
the orally active, selective IP prostacyclin receptor agonist Uptravi(®)
(selexipag) for the treatment of pulmonary arterial hypertension.
Uptravi is indicated for the long-term treatment of pulmonary arterial
hypertension (PAH) in adult patients with WHO functional class (FC) II-III,
either as combination therapy in patients insufficiently controlled with an
endothelin receptor antagonist (ERA) and/or a phosphodiesterase type 5 (PDE-5)
inhibitor, or as monotherapy in patients who are not candidates for these
therapies. Efficacy has been shown in a PAH population including idiopathic and
heritable PAH, PAH associated with connective tissue disorders, and PAH
associated with corrected simple congenital heart disease.
The EU label for Uptravi (originally discovered and synthesized by Nippon
Shinyaku) was based in part on the Phase III GRIPHON study, whose main findings
were published in the New England Journal of Medicine in December 2015. This
placebo-controlled study, the largest ever in PAH, established the
effectiveness, safety and tolerability of Uptravi in PAH patients with WHO
Functional Class II-III. [1]
In GRIPHON, the risk of a primary composite endpoint event, of complication
related to PAH or death from any cause, up to the end of the treatment period,
was reduced by 40% (p<0.001) with selexipag compared to placebo. The treatment
effect was driven by hospitalization and disease progression, which accounted
for 81.9% of the primary endpoint events. The benefit of selexipag was
consistent across pre-specified patient subgroups such as PAH classification,
WHO functional class and use of medication for PAH, which included patients
receiving an ERA and a PDE-5 inhibitor at baseline (n = 376; 32.5%).
Professor Sean Gaine, Consultant Respiratory Physician at Mater Misericordiae
Hospital Dublin, commented: "For many years we have known that the prostacyclin
pathway can be key in treating PAH - yet due to the route of administration of
the existing therapies being so burdensome, the pathway has been largely
underused, with only about 20% of patients ever receiving a prostacyclin at some
point during their PAH treatment. Uptravi, as an innovative oral treatment that
is supported by long-term outcome results, now allows us to offer combination
therapy regimens that target all three established treatment pathways."
Professor Nazzareno Galiè, Head of the Pulmonary Hypertension Center at the
Institute of Cardiology, University of Bologna, added: "The approval of Uptravi
is very positive news for the PAH community in Europe. With Uptravi, for the
first time ever, we see a significant clinical benefit in combination with one
and even two drugs targeting other treatment pathways. Together with its
favorable tolerability profile, this makes Uptravi a treatment option that could
truly change PAH care, for many patients."
Jean-Paul Clozel, M.D. and Chief Executive Officer of Actelion, commented:
"Actelion has a comprehensive portfolio of treatments across the continuum of
care in PAH that provide long-term outcome benefits. We are very pleased with
today's approval of Uptravi by the European Commission as it enables us to offer
this outstanding oral medication, which provides long-term outcome benefits even
for patients receiving background therapy, to PAH patients in Europe. We will
now do our best to make Uptravi available to patients in the European Union as
soon as possible."
The safety of selexipag has been evaluated in a long-term, Phase III placebo
controlled study enrolling 1,156 patients with symptomatic PAH. The mean
treatment duration was 76.4 weeks (median 70.7 weeks) for patients receiving
selexipag versus 71.2 weeks (median 63.7 weeks) for patients on placebo. The
exposure to selexipag was up to 4.2 years.
The most commonly reported adverse reactions related to the pharmacological
effects of Uptravi are headache, diarrhoea, nausea and vomiting, jaw pain,
myalgia, pain in extremity, arthralgia, and flushing. These reactions are more
frequent during the up-titration phase. The majority of these reactions are of
mild to moderate intensity.
The company will now work diligently to make Uptravi available throughout the
European Union as soon as possible and start with the market introduction in
Germany in the near future. In France, a cohort ATU for Uptravi has been
approved, which has commenced for patients insufficiently controlled on an
ERA/PDE-5 inhibitor combination therapy.
###
NOTES TO EDITOR:
REGULATORY STATUS OF SELEXIPAG
Market authorization has so far been received in the US (21 December 2015),
Canada (21 January 2016), New Zealand (17 March 2016), Australia (18 March
2016), South Korea (11 May 2016) and the European Commission (12 May 2016).
Submission of the registration dossier to other health authorities is ongoing,
with regulatory reviews underway in Japan, Switzerland, Taiwan and Turkey.
ABOUT UPTRAVI(®) (SELEXIPAG) [2-7]
Uptravi (selexipag), originally discovered and synthesized by Nippon Shinyaku,
is the only approved oral, selective IP receptor agonist targeting the
prostacyclin pathway in PAH.
Uptravi and its major metabolite selectively target the prostacyclin receptor
(also called IP receptor). The IP receptor is one of 5 major types of prostanoid
receptor (IP, EP, DP, TP, FP). Prostacyclin activates the IP receptor to induce
vasodilation and inhibit proliferation of vascular smooth muscle cells.
ABOUT THE GRIPHON STUDY [1]
GRIPHON, a global, pivotal Phase III study, was designed to demonstrate a
prolongation of time to the first morbidity/mortality event for selexipag
compared to placebo and to evaluate the safety of selexipag in PAH patients.
A total of 1'156 patients were randomized to receive placebo or selexipag.
Utilizing a dosing scheme that titrated patients up to their individualized
doses, dosing in GRIPHON was initiated at 200 micrograms (mcg) twice daily
(b.i.d) and increased weekly in steps of 200 mcg up to a maximum of 1600 mcg
b.i.d. If patients were unable to tolerate a dose, the dose was reduced to the
previously tolerated dose. A primary endpoint event occurred in 397 patients -
41.6% of those in the placebo group and 27.0% of those in the selexipag group
(hazard ratio in the selexipag group as compared with the placebo group,
0.60; 99% confidence interval, 0.46 to 0.78; P<0.001). Disease progression and
hospitalization accounted for 81.9% of the events.
At baseline, almost 80% of patients were receiving oral medication specific for
PAH: either an ERA, a PDE-5 inhibitor, or a combination of the two. The effect
of selexipag with respect to the primary endpoint was similar in the subgroup of
patients who were not receiving treatment for the disease at baseline and in the
subgroup of patients who were already receiving treatment at baseline (including
those who were receiving a combination of both ERA and PDE-5 inhibitor).
Adverse reactions occurring more frequently on Uptravi compared to placebo by
/>=3%, over the course of the study, were headache, diarrhea, jaw pain, nausea,
myalgia, vomiting, pain in extremity, flushing, arthralgia, anemia, decreased
appetite and rash. These adverse reactions were more frequent during the dose
titration phase. Hyperthyroidism was observed in 1% (n=8) of patients on
selexipag and in none of the patients on placebo.
THE ROLE OF THE PROSTACYCLIN PATHWAY [7]
The prostacyclin pathway is one of the 3 best characterized pathways involved in
the pathophysiology and treatment of PAH. Prostacyclin is a prostanoid and
serves as a signaling molecule in the human body. It is produced, like other
vasoactive substances, by endothelial cells. Prostacyclin induces vasodilation,
is anti-proliferative, has anti-inflammatory effects and inhibits platelet
aggregation. In certain disease conditions, the production of prostacyclin by
the endothelium is impaired, allowing for example, the deleterious effects of
excessive levels of endothelin or thromboxane to predominate.
PULMONARY ARTERIAL HYPERTENSION (PAH)
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), prostacyclin receptor agonists, 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. Learn more at
http://www.pahuman.com/
ABOUT NAZZARENO GALIÈ
Professor Nazzareno Galiè heads the Pulmonary Hypertension Centre at
the Institute of Cardiology and is Associate Professor of Cardiology at the
Medical Faculty of the University of Bologna, Italy. He also teaches at the
Postgraduate Medical Schools of Cardiology, Pulmonary Diseases, and Rheumatology
at the University of Bologna. He is Director of the international master's
degree in pulmonary vascular diseases of the University of Bologna since
2007. He has authored over 136 scientific publications indexed in PubMed on
heart failure, heart transplantation and pulmonary hypertension (h-index =
49). Professor Galiè is a Scholar of the Italian Society of Cardiology, Gold
Medal recipient of the Polish Cardiac Society, Fellow of the European Society of
Cardiology (ESC), and Honorary Fellow of the Royal College of Physicians,
UK. He is past-Chairman of the Working Group on Pulmonary Circulation of the ESC
and Co-Chairman of the Joint Task Force of the ESC and the European Respiratory
Society for the guidelines on pulmonary hypertension.
ABOUT SEAN GAINE
Professor Sean Gaine is Consultant Respiratory Physician at Mater Misericordiae
Hospital in Dublin. He completed his residency and fellowship training at the
Johns Hopkins Hospital, Baltimore, USA, and subsequently held faculty positions
at the Johns Hopkins Hospital, and at the University of Maryland School of
Medicine. He established the Pulmonary Hypertension Centre at the Johns Hopkins
Hospital in 1999 and subsequently the National Pulmonary Hypertension Unit in
Dublin. His research interests include new therapeutic agents for the management
of pulmonary vascular diseases. Professor Gaine is a member of numerous
international associations and is Fellow of the College of Chest Physicians, the
Royal College of Physicians in Ireland and the Faculty of Sports and Exercise
Medicine. He is Chief Medical Officer of the Olympic Council of Ireland and led
the medical team at the Olympic Games in Athens, Beijing and London.
ABOUT THE ACTELION / NIPPON SHINYAKU ALLIANCE
In April 2008, Actelion and Nippon Shinyaku entered into an exclusive worldwide
alliance, under which Actelion is responsible for global development and
commercialization of selexipag outside Japan, while the two companies will co-
develop and co-commercialize in Japan. Nippon Shinyaku will receive milestone
payments based on development stage and sales milestones as well as royalties on
any sales of selexipag.
References
1. Sitbon O et al. Selexipag for the Treatment of Pulmonary Arterial
Hypertension. N Engl J Med 2015; 373:2522-33.
2. Kuwano et al. A long-acting and highly selective prostacyclin receptor
agonist prodrug, NS-304, ameliorates rat pulmonary hypertension with unique
relaxant responses of its active form MRE-269 on rat pulmonary artery. J
Pharmacol Exp Ther 2008;326:691-699.
3. Kuwano K et al. 2-[4-[(5,6-diphenylpyrazin-2-yl)(isopropyl)amino]butoxy]-N-
(methylsulfonyl)acetamide (NS-304), an orally available and long-acting
prostacyclin receptor agonist prodrug. J Pharmacol Exp Ther
2007;322(3):1181-1188.
4. Tetsuo Asaki et al. Selexipag: an oral and selective IP prostacyclin
receptor agonist for the treatment of pulmonary arterial hypertension. J.
Med. Chem., Just Accepted Manuscript. DOI: 10.1021/acs.jmedchem.5b00698.
Web: 20 Aug 2015.
5. Morrison et al. Selexipag: a selective prostacyclin receptor agonist that
does not affect rat gastric function. J Pharmacol Exp Ther 2010;335:249-255.
6. Morrison et al. Differential effects of selexipag and prostacyclin analogs
in rat pulmonary artery. J Pharmacol Exp Ther 2012;343:547-555.
7. Simonneau G, Lang I, Torbicki A, Hoeper MM, Delcroix M, Karlocai K, Galie N.
Selexipag, an oral, selective IP receptor agonist for the treatment of
pulmonary arterial hypertension Eur Respir J 2012; 40: 874-880.
8. Mubarak KK. A review of prostaglandin analogs in the management of patients
with pulmonary arterial hypertension. Respir Med 2010;104:9-21.
NIPPON SHINYAKU
For further information on Nippon Shinyaku please visit:
http://www.nippon-shinyaku.co.jp/english/index.html
ACTELION LTD
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 type cutaneous T-cell lymphoma.
Founded in late 1997, with now over 2,500 dedicated professionals covering all
key markets around the world including Europe, 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 SMI®). All trademarks
are legally protected.
For further information please contact:
Andrew C. Weiss
Senior Vice President, Head of Investor Relations & Corporate Communications
Actelion Pharmaceuticals Ltd, Gewerbestrasse 16, CH-4123 Allschwil
+41 61 565 62 62
http://www.actelion.com
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", "believes", "expects", "may", "are expected
to", "will", "will continue", "should", "would be", "seeks", "pending" or
"anticipates" or similar expressions, or by discussions of strategy, plans or
intentions. 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:
http://hugin.info/131801/R/2013097/745974.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
[HUG#2013097]
Unternehmensinformation / Kurzprofil:
Datum: 17.05.2016 - 07:00 Uhr
Sprache: Deutsch
News-ID 471481
Anzahl Zeichen: 19973
contact information:
Town:
Allschwil
Kategorie:
Business News
Diese Pressemitteilung wurde bisher 284 mal aufgerufen.
Die Pressemitteilung mit dem Titel:
"Actelion is granted marketing authorization for Uptravi (selexipag) in pulmonary arterial hypertension by the European Commission"
steht unter der journalistisch-redaktionellen Verantwortung von
Actelion Pharmaceuticals Ltd (Nachricht senden)
Beachten Sie bitte die weiteren Informationen zum Haftungsauschluß (gemäß TMG - TeleMedianGesetz) und dem Datenschutz (gemäß der DSGVO).
