Friday August 10, 3:13 pm Eastern Time
Press Release
SOURCE: Actelion Ltd
FDA Advisory Committee Votes Unanimously to
Recommend Approval of Tracleer for Treatment of
Pulmonary Arterial Hypertension
ALLSCHWIL, Switzerland--(BUSINESS WIRE)--Aug. 10, 2001--Actelion Ltd.
(SWX:ATLN) today announced that the Cardiovascular and Renal Drugs Advisory
Committee voted unanimously to recommend to the U.S. Food and Drug Administration
(FDA) the approval of the oral dual endothelin receptor antagonist Tracleer(TM) (bosentan)
for the treatment of pulmonary arterial hypertension (PAH).
PAH is a life-threatening chronic condition that can severely compromise the function of the
lungs and heart. While the FDA is not bound by the recommendation, it traditionally follows
the Committee's advice.
``We will continue to work closely with the FDA to ensure that we can bring Tracleer, the
first oral therapy for pulmonary arterial hypertension, to patients in an expeditious manner,''
said Jean-Paul Clozel, CEO of Actelion. ``The FDA Advisory Committee recommendation
validates our belief in the therapeutic potential of endothelin receptor antagonism.''
The Committee based their recommendation to approve Tracleer on two successfully
concluded pivotal trials, the larger of which is known as the BREATHE-1 (Bosentan:
Randomized Trial of Endothelin Receptor Antagonist THErapy) trial. BREATHE-1 principle
investigator Lewis Rubin, MD, Professor of Medicine and Director, Pulmonary and Critical
Care Medicine, University of California at San Diego commented: ``We are nearing a
milestone in the treatment of pulmonary arterial hypertension. For the first time, patients and
their families can have realistic hope that an oral treatment demonstrating very promising
results may soon be made available.''
In the 213-patient BREATHE-1 trial, twice-daily Tracleer (125 mg b.i.d. and 250 mg b.i.d.)
demonstrated -- in both primary and secondary PAH -- statistically significant improvements
versus placebo in the primary efficacy endpoint of the study, exercise capacity. The overall
treatment effect for both doses of Tracleer combined was a 44 meter improvement in
walking distance as measured by a six-minute walk test, compared to placebo (p=0.0002).
Treatment with Tracleer also was associated with a significant delay in the time to clinical
worsening as defined as death, hospitalization, worsening PAH or initiation of intravenous
therapy (p=0.0015) and a significant improvement in functional status (p<0.05).
Tracleer was well tolerated overall. In BREATHE-1, the incidence of liver enzyme elevations, defined as above three times the
upper limit of normal (ULN), was 13 percent in the 125 mg b.i.d. group and 14 percent in the 250 mg b.i.d. group. These
dose-related elevations were usually transient in nature and returned to normal in all patients upon dose-reduction or
discontinuation. No patient in the 125 mg group discontinued treatment due to elevated liver enzymes, in contrast to three
patients on 250 mg whose liver enzyme values returned to normal following permanent drug discontinuation.
Approximately 100,000 people in the U.S. 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, such as scleroderma, lupus and
HIV/AIDS and the use of certain appetite suppressants.
The first signs of the disease, such as mild shortness of breath, fatigue and difficulty exercising, are so subtle that the disease is
often either misdiagnosed or not diagnosed until the patient's condition is far advanced. The survival rate for PAH in untreated
patients is only 40 to 55 percent at two years from the onset of symptoms. Once patients reach more advanced stages of PAH
(WHO Class III and IV), they often have no choice but to go on prostacyclin therapy, which requires a 24-hour infusion pump
and an intravenous line implanted through the chest directly into the patient's heart. Ultimately, many patients require lung
transplantation.
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 to the European Authorities in February 2001. Tracleer also is currently under review in
Switzerland, Canada and Australia. U.S., European and Australian regulatory authorities have granted Tracleer Orphan Drug
status in pulmonary arterial hypertension. The company is further studying Tracleer for children suffering from PAH, as well as
the concomitant use of Tracleer in patients who receive intravenous prostacyclin therapy.
Tracleer is currently also in Phase III trials for the treatment of chronic heart failure (CHF). Upon successful completion of this
program, Genentech Inc. has the option to become a co-promotion partner for Tracleer in both indications (CHF and PAH) in
the United States.
Actelion Ltd, a biopharmaceutical company headquartered in Allschwil/Basel, Switzerland, is a leading player 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(TM) and Veletri(TM) are in 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 SWX Swiss Exchange (SWX New Market: ATLN).
NOTE TO EDITORS: In the fifth paragraph, there is a ``less than'' symbol between (p and 0.05). This symbol may not appear
properly in some systems.
Contact:
Actelion Ltd, Allschwil
Roland Haefeli, +1 202 302 47 38 |
