CONSCIOUS-2 study with clazosentan does not meet primary endpoint
ALLSCHWIL/BASEL, SWITZERLAND - 27 September 2010 - Actelion Ltd (SIX: ATLN) announced today the initial results of CONSCIOUS-2 a clinical study evaluating the safety and efficacy of clazosentan in reducing vasospasm-related morbidity and all-cause mortality in clipped patients following aneurysmal subarachnoid hemorrhage (aSAH).
The primary endpoint showed a non-significant relative risk reduction of 17 percent in favor of clazosentan (p=0.1). The safety profile of clazosentan in CONSCIOUS-2 was comparable to previous studies with the compound in this disease.
Jean-Paul Clozel, M.D. and Chief Executive Officer of Actelion commented: "These are, of course, disappointing results. Having embarked upon such a complex study, both in terms of design and execution, I must commend the exceptional efforts of all involved delivering a high-quality study."
Jean-Paul Clozel continued: "Actelion will continue to focus on growing its existing business. With four marketed products, Actelion is generating the necessary revenues to continue to invest appropriately in clinical studies for our more than 10 development compounds."
In regards to the ongoing CONSCIOUS-3 study in patients with aSAH that underwent coiling to secure their aneurysm, Actelion will discuss the appropriate course of action with the Steering Committee. The company will provide an update on the clazosentan development program in its upcoming Q3 reporting, scheduled for Thursday, 21 October 2010.
CONSCIOUS-2 (Clazosentan to Overcome Neurological iSChemia and Infarct OccUrring after Subarachnoid hemorrhage) investigated the potential clinical benefits of clazosentan through the primary endpoint of vasospasm-related morbidity and all-cause mortality, which includes neurological deterioration, new brain infarcts, introduction of vasospasm rescue therapy, or death from any cause.
CONSCIOUS-2 was a global study which concluded enrollment with over 1,150 patients with aSAH and aneurysmal surgical clipping, from more than 100 centers. Patients were randomized 2:1 to receive either 5 mg/h of clazosentan, or placebo.
Notes to the Editor
About Cerebral vasospasm as a consequence of aneurysmal subarachnoid hemorrhage
Aneurysmal subarachnoid hemorrhage (aSAH) is a life-threatening condition affecting over 85,000 people in the EU, US and Japan every year. This condition occurs when the rupture of an aneurysm on the cerebral vessels leads to release of blood into the subarachnoid space of the brain. Endovascular coiling or microsurgical clipping is usually required to stop the bleeding and prevent further episodes.
Cerebral vasospasm following SAH causes the intracranial arteries to constrict thus diminishing blood flow to the brain. It is a significant predictor of poor outcome and the leading potentially treatable cause of mortality and morbidity in these patients. Vasospasm is unpredictable in nature and seen in over 67% of untreated patients with angiography at the time of maximum spasm, around the end of the first week. It becomes symptomatic in about half of these patients. Currently, there is no effective treatment for the prevention and treatment of the severe complications following vasospasm.
CONSCIOUS-3 is a Phase III study evaluating the efficacy and safety of two doses (5 or 15 mg/h) of clazosentan versus placebo in patients post-aSAH treated by endovascular coiling. The primary endpoint is identical to that of CONSCIOUS 2. Until the end of September 2010, the study enrolled close to 600 patients out of 1500 planned.
CONSCIOUS-1 was a multi-center, international, double-blind, randomized, placebo-controlled, parallel-group, dose-finding study to evaluate the efficacy of three dose levels of clazosentan (15, 5 and 1mg/hour) in preventing the occurrence of cerebral vasospasm following aSAH in patients who underwent either clipping or coiling to stop the initial bleed, assessed by angiography.
CONSCIOUS-1 showed a strong treatment effect on the primary endpoint. Clazosentan significantly reduced moderate/severe vasospasm at all tested doses, with a relative risk reduction compared to placebo of 65% at the highest dose. A post-hoc analysis showed a trend in favor of reducing morbidity/mortality related to vasospasm using central assessment.
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.
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, 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 2,400 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®).