Tuesday, May 1, 2001
Allschwil, Switzerland and South San Francisco, Calif. -- May 1, 2001 --Actelion Ltd. (SWX New Market: ATLN) and Genentech, Inc. (NYSE: DNA) announced positive results today from a Phase III trial (BREATHE-1) of the first orally active endothelin receptor antagonist, Tracleeru (bosentan) in pulmonary arterial hypertension (PAH). PAH is a potentially life-threatening chronic condition that can severely compromise the function of the lungs and heart. In the BREATHE-1 trial, Tracleer demonstrated statistically significant improvements over placebo in the primary efficacy endpoint of the study, exercise capacity.
"For the first time in a large scale clinical trial, an oral agent has demonstrated the potential to dramatically improve patient outcome in PAH," said BREATHE-1 lead investigator Lewis Rubin, MD, Professor of Medicine/Director, Pulmonary and Critical Care Medicine, University of California at San Diego. "These findings demonstrate Tracleer may be an important new treatment for PAH patients that is convenient to administer orally."
BREATHE-1 (Bosentan: Randomized Trial of Endothelin Receptor Antagonist THErapy for Pulmonary Hypertension), a double-blind, placebo-controlled, multicenter trial, was designed to evaluate the safety and efficacy of two twice-daily dose levels of Tracleer (125 mg BID and 250 mg BID). The primary endpoint of the study was the change from baseline in exercise capacity, as measured by a six-minute walk test at 16 weeks. The 213-patient trial randomized patients into three arms, the first receiving a starting dose of 62.5 mg BID of Tracleer doubled to 125 mg BID after four weeks of treatment, the second receiving a starting dose of 62.5 mg BID increased to 250 mg BID after four weeks, and the third arm receiving placebo.
Patients receiving Tracleer were able to walk statistically significantly greater distances in the six-minute walk test after 16 weeks, compared to placebo. The overall treatment effect for both doses of Tracleer combined was a 44 meter improvement in walking distance, compared to placebo (p=0.0002). This effect was statistically significant for both Tracleer dose groups. Significant positive effects were also observed on clinically important secondary endpoints.
"These initial results confirm the findings from an earlier trial of Tracleer and highlight its potential as a treatment for pulmonary arterial hypertension," said Hal V. Barron, MD, Genentech's senior director of Cardiopulmonary Clinical Research.
Tracleer was well tolerated and the overall incidence of adverse events was similar across the three treatment groups. The incidence of elevated liver enzymes (reported as an adverse event) was 3% for placebo, 5% for 125 mg Tracleer BID, and 14% for 250 mg Tracleer BID None of these elevations in the Tracleer groups were judged serious by the investigators. There was a higher incidence of worsening of PAH in the placebo group (19%) versus the Tracleer treatment group (7%). The overall rate of serious adverse events was similar between Tracleer and placebo treated patients.
"The positive findings of the Tracleer BREATHE-1 study reinforce our belief that the class of endothelin receptor antagonists may have an important clinical role to play in Pulmonary Arterial Hypertension," said Jean-Paul Clozel, Actelion Ltd. Chief Executive Officer and company co-founder. "We will continue to work closely and expeditiously with regulatory authorities to bring Tracleer to patients suffering pulmonary arterial hypertension."
Actelion submitted a New Drug Application (NDA) for Tracleer in Pulmonary Arterial Hypertension to the U.S. Food and Drug Administration in November 2000 and the European Authorities in February 2001. Filing was based upon an earlier study of similar design. The BREATHE-1 data will supplement these submissions, as well as submissions pending in Canada and Australia. The United States, European and Australian regulatory authorities have granted Tracleer Orphan Drug status in pulmonary arterial hypertension.
Actelion and Genentech signed an agreement in December 2000 for the co-promotion of Tracleer for pulmonary arterial hypertension and chronic heart failure in the United States, with Actelion taking the lead in the development and commercialization. Tracleer is currently in Phase III trials for the treatment of chronic heart failure.
Pulmonary arterial hypertension is a potentially life-threatening chronic condition that can involve the lungs, heart and other organs. Pulmonary hypertension carries a survival rate in untreated patients of only 40 to 55 percent at two years from the onset of symptoms.
Studies estimate that approximately 100,000 people in the United States and Europe are afflicted with either primary pulmonary arterial hypertension or secondary forms of the disease related to conditions or tissue disorders that affect the lungs. One available treatment option for PAH involves use of IV medication that must be administered 24 hours a day and seven days a week via a central intravenous catheter.
Actelion Ltd, a biopharmaceutical company headquartered in Allschwil, Switzerland, is the global leader in creative science related to the endothelium of the single layer of cells separating every blood vessel from the blood stream. Actelion concentrates on developing and bringing innovative drugs to patients. Tracleer and Veletriu (tezosentan), its two flagship drugs, are in late stage development for several cardiovascular disorders, including chronic and acute heart failure as well as pulmonary arterial hypertension. In addition, Actelion is conducting drug discovery programs in cardiovascular diseases, malaria, Alzheimer's disease and cancer. Actelion is quoted on the Swiss Stock Exchange (SWX New Market: ATLN).
Genentech, Inc., is a leading biotechnology company that discovers, develops, manufactures and markets human pharmaceuticals for significant unmet medical needs. Fourteen of the currently approved biotechnology products stem from Genentech science. Genentech markets nine biotechnology products directly in the United States. The company has headquarters in South San Francisco, California, and is traded on the New York Stock Exchange under the symbol DNA.
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