[ Actelion/DNA, endothelin receptor antagonist ]
Wednesday May 2, 12:00 am Eastern Time
Press Release
Oral Endothelin Receptor Antagonist Tracleer Meets
Primary Endpoint in Pulmonary Arterial
Hypertension Study
ALLSCHWIL, Switzerland and SOUTH SAN FRANCISCO, Calif.--(BW
HealthWire)--May 1, 2001--
Actelion and Genentech Announce Positive Results of Tracleer
Phase III Trial; Data Will Supplement US and
European Market Authorization Filing
Actelion Ltd. (SWX New Market:ATLN) and Genentech, Inc. (NYSE:DNA - news)
announced positive results today from a Phase III trial (BREATHE-1) of the first orally
active endothelin receptor antagonist, Tracleer(TM) (bosentan) in pulmonary arterial
hypertension (PAH). PAH is a potentially life-threatening chronic condition that 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 b.i.d.
and 250 mg b.i.d.). 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 b.i.d., and
14% for 250 mg Tracleer b.i.d. 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 - 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 Veletri(TM) (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.
Contact:
Genentech
Shelley Schneiderman, 650/823-2570 or 650/225-7848
(Media)
Mike Burchmore 650/225-8852
(Investor)
gene.com
or
Actelion
Roland Haefeli, +41-61-487-34-58
(Media)
actelion.com |
