ALLSCHWIL/BASEL, Switzerland, June 7, 2004 (PRIMEZONE) -- Actelion Ltd (SWX:ATLN):
-- Pivotal tezosentan (VeletriTM) study in Acute Heart Failure
passes first futility analysis
-- Second futility analysis scheduled for Q4 2004
-- Other advanced programs with bosentan (Tracleer(r)) in digital
ulcerations and pulmonary fibrosis enrolling on schedule
-- Bosentan in metastatic melanoma well tolerated at high doses
-- No further development with tezosentan in hepatorenal syndrome
-- Additional resources for early clinical program with urotensin-II
receptor antagonist in diabetic nephropathy
Actelion Ltd (SWX:ATLN) today announced that the pivotal VERITAS study (Value of Endothelin Receptor Inhibition with Tezosentan in Acute heart failure Study) is continuing.
As specified in the clinical trial plan, an independent drug safety monitoring board (DSMB) has performed a first futility analysis after half of the up to 1,800 patients planned for enrolment in the study were exposed to standard therapy plus either tezosentan or placebo. This recommendation to continue indicates that the trial has a chance of achieving statistical significance in at least one of the two co-primary endpoints, mortality/morbidity or dyspnea reduction.
A second interim analysis is scheduled sometime in the last quarter of 2004, after approximately 75 percent of the trial is enrolled. Should the DSMB again advise trial continuation, final results may become available in spring 2005.
Ongoing advanced clinical studies with Tracleer(r) recruiting on schedule
In its advanced clinical development program, Actelion is focusing its efforts on endothelin-related diseases in a number of areas of high unmet medical need. All these trials involving the orally available dual endothelin antagonist bosentan (Tracleer(r)), currently approved for the treatment of Pulmonary Arterial Hypertension (PAH), are now recruiting as scheduled.
- The clinical program initiated in the fall of 2003 evaluating safety and efficacy of bosentan (Tracleer(r)) in the idiopathic and scleroderma-related form of Pulmonary Fibrosis have enrolled approximately 70 percent of the 132 patients required in each BUILD trial (Bosentan Use in Interstitial Lung Diseases). Full enrolment is expected towards the end of the year. With patients followed for at least 12 months, final study results of the two studies may become available in late 2005 or early 2006.
- The clinical program initiated in the fall of 2003 evaluating the safety and efficacy of bosentan (Tracleer(r)) in digital ulcers (RAPIDS-2, RAndomized, double-blind, Placebo-controlled, multi-center study to assess the effect of bosentan on healing and prevention of Ischemic Digital ulcers in patients with systemic Sclerosis) has now enrolled 80 percent of the 180 patients required. Full enrolment is expected either late 2004 or early 2005. With patients followed for up to nine months, final study results may become available in early 2006.
Actelion is also on track to initiate a clinical trial with Tracleer(r) in Class II PAH patients to expand the existing labeling in this indication. The study EARLY (Endothelin Antagonist tRial in miLdly sYmptomatic PAH patients) is foreseen to recruit the first out of 170 patients in late 2004. With patients being followed for at least six months, study results may become available in 2006.
Zavesca(r) program in late onset Tay-Sachs disease fully enrolled The clinical programs with Zavesca(r), currently approved as a treatment option for type 1 Gaucher's disease, are making progress. A small, but potentially label-enabling study in late onset Tay-Sachs disease has been fully enrolled with 30 adult patients suffering from this severe neurological and life-shortening disease. Study results may therefore become available either late 2004 or early 2005.
Two other studies evaluating the safety and efficacy of Zavesca(r) in two additional neurological lipid-storage diseases, Type 3 Gaucher and Niemann-Pick type C are underway and results may become available in mid-2005.
Advanced clazosentan discussions with regulatory authorities
Following encouraging Phase IIa results with the intravenous endothelin receptor antagonist clazosentan evaluating the prevention of arterial vasospasm following surgery for cerebral bleeding events (subarachnoid hemorrhage), Actelion has initiated discussions with regulatory authorities worldwide regarding the further clinical program.
These discussions are very advanced and if agreement is reached, Actelion may be able to start enrolment in the full-fledged clinical IIb/III program before the end of 2004.
First safety findings for bosentan in metastatic melanoma
In the summer of 2003, Actelion initiated a first pilot study evaluating in an open-label, non-randomized setting the safety and efficacy of 500 mg bosentan (Tracleer(r)) twice a day in 35 patients with stage IV metastatic malignant melanoma. Patients with this advanced form of spreading skin cancer have an average life expectancy of six to nine months.
The preliminary safety analysis seems to indicate that the drug is well tolerated even at doses four times higher than what is prescribed today in the approved indication, pulmonary arterial hypertension (125 mg twice a day). In this pilot study, three out of 35 patients discontinued treatment due to elevated liver enzyme levels that returned to normal upon cessation of treatment. Efficacy analysis is ongoing. Actelion expects to discuss the full data set with experts in the field in the coming weeks to prepare for scientific presentation.
Shift of resources from tezosentan in HRS to urotensin-II receptor antagonist in diabetic nephropathy
In spring 2003, Actelion initiated a pilot program evaluating tezosentan as a potential treatment option for a rare liver-kidney disease, Hepatorenal Syndrome (HRS). Preliminary analysis of the program indicates that while the drug seems to be well tolerated, the pre-defined efficacy level to warrant a full-fledged clinical program has not been achieved. The full data set will be discussed with experts in the field in the coming weeks.
In late 2003, Actelion initiated a pilot program evaluating the first orally available urotensin-II receptor antagonist as a potential treatment option for kidney failure associated with diabetes (diabetic nephropathy). Given encouraging preliminary observations in this program, Actelion has decided to initiate a third study within that pilot program to ensure that the company has additional supportive data sets available when a decision about a full-fledged Phase IIb/III clinical program is made in 2005.
About Tracleer(r) in Pulmonary Arterial Hypertension (PAH)
Tracleer(r), the first oral dual endothelin receptor antagonist, is approved for the treatment of pulmonary arterial hypertension (PAH) and made available by Actelion subsidiaries in the United States, the European Union, Australia, Canada and Switzerland. In Japan, Tracleer(r) has been filed for marketing approval. In clinical trials leading to the marketing approval of the drug, approximately 11 % of PAH patients receiving Tracleer(r) experienced abnormal but reversible liver enzyme elevations. It is therefore important that patients undergo monthly liver monitoring. Due to the risk of birth defects, women who are pregnant, or of childbearing age who do not use a reliable method of contraception, must not take Tracleer(r).
About Actelion Ltd
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 as well as 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).
For further information please contact:
Actelion Ltd, Gewerbestrasse 16, CH-4123 Allschwil
Investor Contact Roland Haefeli +41 61 487 34 58
+1 650 624 6936
Media Contact Peter Engel +41 61 487 36 28
+1 650 624 6996
http://www.actelion.com
Conference Call
Actelion will host an Investor Conference Call and discussion/Q&A on Monday, 7 June 2004, 15.30 CET / 09.30 AM EST / 14.30 GMT
Dial: +41 (0)91 610 56 00 (Europe)
+1 (1)866 291 41 66 (U.S.)
+44 (0)207 107 06 11 (U.K.)
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