Healthcare Industry News: TRACLEER
News Release - June 19, 2006
Actelion: Preliminary Results of CONSCIOUS-1 -- Significant Reduction of Cerebral Vasospasm in Patients With Aneurysmal Subarachnoid Hemorrhage -- Primary Endpoint AchievedNo Overall Effect Seen in Secondary Clinical Outcome Endpoints
Further Data Analysis Needed to Determine Future Development Path
ALLSCHWIL, Switzerland, June 19, 2006 (Healthcare Sales & Marketing Network) -- Actelion Ltd. (Other OTC:ALIOF.PK ) (Swiss:ATLN.SW ) announced today that preliminary analysis of the dose-finding study CONSCIOUS-1 (Clazosentan to Overcome Neurological iSChemia and Infarct OccUrring after Subarachnoid hemorrhage) indicates that all three doses of i.v clazosentan tested (15, 5 and 1 mg/hour) have reached statistical significance versus placebo for the primary endpoint, the reduction in the occurrence of moderate or severe cerebral vasospasm, as measured by cerebral angiography at day 9 (plus/minus 2 days) post-aneurysm rupture compared to placebo.
The effect was dose-related and most significantly seen with the dose of 15 mg/hour, a relative risk reduction compared to placebo of 65 percent (p less than 0.0001). In the study, the significant reduction in cerebral vasospasm did not translate into an overall clinical benefit as assessed by the chosen key secondary composite endpoint: occurrence of morbidity/mortality (death, new cerebral infarcts, delayed ischemic neurological deficit, rescue therapy) up to week 6.
In the study, treatment with clazosentan was associated with more adverse events than placebo, mainly related to vasodilatory effects such as hypotension and fluid retention.
Isaac Kobrin, MD and Head of Clinical Development, commented: ``The information generated from the preliminary analysis of CONSCIOUS-1 demonstrates significance in terms of clazosentan decreasing cerebral vasospasm in a dose-related fashion.''
Isaac Kobrin concluded: ``A full data analysis and consultation with clinical experts is essential to better understand the apparent disconnect in this study between the significant reduction in cerebral vasospasm and clinical outcome assessed by the endpoint chosen. This full data analysis will determine the future development path.''
CONSCIOUS-1 (Clazosentan to Overcome Neurological iSChemia and Infarct OccUrring after Subarachnoid hemorrhage) was a multi-centre, international, double-blind, randomized, placebo-controlled, parallel group, dose-finding study to evaluate the efficacy of 3 dose levels of clazosentan (15, 5 and 1mg/hour) in preventing the occurrence of cerebral vasospasm following SAH who underwent either clipping or coiling to stop the initial aneurismal bleed, assessed by angiography. As a secondary endpoint, the study also evaluated the ability of clazosentan to reduce the occurrence of early morbidity/mortality as well as overall safety and tolerability of the drug.
CONSCIOUS-1 recruited 413 patients in 52 centers in 11 countries worldwide and was initiated after promising pre-clinical and clinical data that was published in the Journal of Neurosurgery in July 2005 (a).
(a) Vajkoczy P, Meyer B, Weidauer S et al. Clazosentan (AXV-034343), a selective endothelin A receptor antagonist, in the prevention of cerebral vasospasm following severe aneurysmal subarachnoid hemorrhage: a randomized, double-blind, placebo-controlled, multicenter, Phase IIa study. Journal of Neurosurgery July 2005. 103, 9-17.
NOTES TO THE EDITOR:
About cerebral vasospasm following SAH
Intravascular coiling or surgical clipping is usually required to secure the aneurysm so as to stop the bleeding and prevent further episodes. The vasospasm following SAH occurs when the acute rupture of an aneurysm of the cerebral vessels releases blood into the subarachnoid space of the brain. This blood progressively breaks down in the brain acutely up-regulating the release of endothelin in the subarachnoid space.
Endothelin, a known mediator of vasospasm in the cerebral vasculature, provides a rationale for the use of clazosentan, an intravenous endothelin receptor antagonist, for the prevention of vasospasm.
About aneurysmal SAH
A cerebral aneurysm refers to a blood vessel within the brain that weakens over time and undergoes widening. This usually occurs at the junctions of the large arteries at the base of the brain. As the blood vessel weakens, it begins to bulge out like a balloon. The larger the balloon becomes, the greater the risk it may burst, resulting in hemorrhage (bleeding) into the subarachnoid space (membranous space surrounding the brain) and the ensuing spasm (uncontrollable tightening) of the brain blood vessels, leading to oxygen shortage in the brain cells.
Over a quarter of people (27%) die within the first week following an aneurysmal subarachnoid hemorrhage without treatment. Rebleeding occurs in 50% of the aneurysms within the first six months, and about half of the patients die after a rebleed and a further 20% become disabled.
Actelion Ltd. is a biopharmaceutical company with its corporate headquarters in Allschwil/Basel, Switzerland. Actelion's first drug TRACLEER(r), an orally available dual endothelin receptor antagonist, has been approved as a therapy for pulmonary arterial hypertension. Actelion markets TRACLEER(r) 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 focuses on the discovery, development and marketing of innovative drugs for significant unmet medical needs. Actelion shares are traded on the SWX Swiss Exchange (ticker symbol: ATLN).
Actelion will host an Investor Conference Call and discussion/Q&A on Monday, 19 June 2006, at 07.30 CEST / 01.30 a.m. EDT / 06.30 BST
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