Actelion Pharmaceuticals Ltd : Actelion provides update on Phase III GRIPHON
study with selexipag in pulmonary arterial hypertension - Study continues
Actelion Pharmaceuticals Ltd / Actelion provides update on Phase III GRIPHON
study with selexipag in pulmonary arterial hypertension - Study continues .
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ALLSCHWIL, SWITZERLAND - 08 May 2013 - Actelion Ltd (SIX: ATLN) announced
today that the Independent Data Monitoring Committee (DMC) has informed the
company of its unanimous recommendation to continue the pivotal Phase III
study, GRIPHON. In addition the DMC had no recommendations for any
modification in study design or procedures.
The placebo-controlled, randomized GRIPHON study is designed to evaluate the
efficacy and safety of selexipag in 1'150 patients with pulmonary arterial
hypertension (PAH) in an event-driven morbidity/mortality study.
Selexipag is an orally available selective IP receptor agonist that - in a
Phase II study - showed a significant reduction in pulmonary vascular
resistance (PVR). Pulmonary arterial hypertension (PAH) is a syndrome
characterized by a progressive increase in pulmonary vascular resistance.
As described in the study protocol, the GRIPHON DMC was scheduled to perform
an interim analysis at around two thirds of the overall foreseen
morbidity/mortality events were observed, in addition to the evaluation of
patient safety in the study. The goal of the interim analysis was to assess
whether study continuation was warranted based on the primary objective of
demonstrating morbidity/mortality benefits.
With the interim analysis now successfully concluded and the DMC recommending
study continuation as planned, final study results of this event-driven study
are now expected by mid-2014.
Notes to Editor:
GRIPHON, (Prostacyclin (PGI2) Receptor agonist in pulmonary arterial
hypertension) is a multicenter, double-blind, placebo-controlled trial
evaluating the long-term efficacy and safety of oral selexipag in patients
with pulmonary arterial hypertension.
GRIPHON is close to full enrollment with 1'143 patients randomized, of the
targeted 1'150, and represents the largest randomized, controlled study in PAH
patients. This pivotal study is designed to demonstrate a reduction in risk of
morbidity/mortality events of selexipag treatment compared to placebo and
evaluate the safety of the selexipag in PAH patients. Results are expected to
be available mid-2014.
Selexipag, originally discovered and synthesized by Nippon Shinyaku, is a
first-in-class, potent, orally available, selective IP receptor agonist.
Selexipag has major potential as a novel treatment of pulmonary arterial
Results of a Phase II, 43-patient, placebo-controlled, double-blind study,
where patients were randomized in a 3:1 ratio receiving selexipag or placebo
on top of PDE5 and/or ERA, showed a statistically significant reduction in
pulmonary vascular resistance (PVR; primary parameter for the study). The
treatment effect was shown to be 30.3% after 17 weeks of treatment (p=0.0045).
Results also showed an encouraging numerical improvement in 6-minute walk
distance (6MWD), which was a secondary endpoint of this trial. Selexipag was
well tolerated and the safety profile was in-line with the expected
pharmacologic effect. 
ABOUT PULMONARY ARTERIAL HYPERTENSION (PAH)
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
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 3 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.
Despite these advances in PAH, survival rates are unacceptably low and PAH
Prostacyclin and prostaglandins are types of prostanoids. Endothelial cells
produce several vasoactive chemical factors, among them prostacyclin (PGI),
which induce vasodilation of blood vessels and inhibit smooth muscle cell
proliferation and platelet aggregation. The peptide endothelin is also
produced by the endothelium, and is a potent constrictor of blood vessels and
promotes cell proliferation. In a normal healthy state, prostacyclin helps
counter-balance the actions of endothelin. In certain disease conditions,
however, production of prostacyclin by the endothelium is impaired, allowing
the deleterious effects of excessive levels of endothelin to predominate.
ABOUT PROSTACYCLIN RECEPTOR AGONISM
The IP receptor (PGI (prostacyclin) receptor) is one of 5 types of
prostanoid receptor available to prostanoid replacement therapies.
Prostacyclin activates the IP receptor inducing vasodilation and inhibiting
proliferation of vascular smooth muscle cells. With selective IP receptor
agonism, the risk of side effects mediated by activation of other prostanoid
receptors may be minimized.
Actelion is developing a first-in-class, orally available, selective IP
receptor agonist that mimics the actions of endogenous prostacyclin for the
treatment of PAH.
ABOUT THE ACTELION / NIPPON SHINYAKU ALLIANCE
Actelion and Nippon Shinyaku entered into an exclusive worldwide alliance in
April 2008 to collaborate on selexipag, a first-in-class orally-available,
selective IP receptor agonist for patients suffering from pulmonary arterial
hypertension (PAH). This compound was originally discovered and synthesized by
Nippon Shinyaku. Phase II evaluation has been completed, and a Phase III
program in PAH patients has been initiated. 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.
1.Kuwano et al. NS-304, an orally available and long-acting prostacyclin
receptor agonist prodrug. J Pharmacol Exp Ther 2007;322:1181-1188.
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.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
4.Mubarak KK. A review of prostaglandin analogs in the management of
patients with pulmonary arterial hypertension. Respir Med 2010;104:9-21.
For further information on Nippon Shinyaku please visit:
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 2,300 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^®).
For further information please contact:
Vice President, Head of Investor Relations & Corporate Communications
Actelion Pharmaceuticals Ltd, Gewerbestrasse 16, CH-4123 Allschwil
+41 61 565 62 62
+1 650 624 69 36
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