Actelion Pharmaceuticals US, Inc. announced positive results from two trials demonstrating that Tracleer(R) (bosentan) may be safe and effective as a combination therapy
for the treatment of pulmonary arterial hypertension (PAH). Data from both
studies suggest that Tracleer, when given in combination with sildenafil,
is well-tolerated and improves hemodynamics in PAH patients. The data were
presented at CHEST 2007, the annual meeting of the American College of
Chest Physicians, taking place in Chicago.
COMPASS-1 (Effects of Combination Of bosentan and sildenafil versus
sildenafil Monotherapy on morbidity and mortality in symptomatic PAtientS
with pulmonary arterial hypertenSion) was the first clinical trial to
provide detailed hemodynamic information on the combination of Tracleer and
sildenafil, and showed that the combination of acute oral sildenafil
together with long-term Tracleer therapy significantly reduced pulmonary
vascular resistance (PVR).
Data from the sildenafil cohort of the Phase 3 EARLY (Endothelin
Antagonist tRial in miLdlY symptomatic PAH patients) study showed that
Tracleer improved hemodynamics and suggested a delay in disease progression
in sildenafil-treated mildly symptomatic PAH patients. The EARLY trial was
the first study of its kind to evaluate the benefit of Tracleer and
sildenafil combination therapy.
"Despite the availability of effective PAH therapies, we are not
meeting key treatment goals for long-term stabilization in the majority of
patients," said Nazzareno Galie from the University of Bologna, Italy, also
the lead author of the COMPASS-1 study. "Given the progressive and
destructive nature of this disease, combining therapies with different
modes of action has become an important focus for research, and these
results support our belief that adding bosentan to sildenafil could
potentially slow disease progression."
"The results of the COMPASS-1 and EARLY studies demonstrate that
Tracleer, when used alone or in combination with other therapies, appears
to be well-tolerated and an effective treatment option for patients with
PAH," said Craig Hopkinson, vice president of U.S. medical at Actelion.
"Actelion is committed to conducting studies with Tracleer in combination
with other approved therapies in order to evaluate the drug's effect in a
combination therapy setting on delaying disease progression and improving
patient care."
COMPASS-1 Study Details and Results
The COMPASS-1 trial assessed the acute hemodynamic effects of
sildenafil in combination therapy with Tracleer. The open-label,
uncontrolled, prospective, multicenter study evaluated 45 patients
receiving Tracleer and measured PVR with the addition of inhaled nitric
oxide (iNO) and a single 25mg dose of sildenafil.
The % change in PVR induced by iNO and sildenafil was similar.
Sildenafil lowered mean PVR by 15.1% from 828+/-724 to 721+/-651
dyne.s.cm-5 60 minutes after intake (p