Actelion announces results of the MAESTRO study with macitentan in patients with pulmonary arterial hypertension due to Eisenmenger Syndrome - Seite 2

A 20% reduction of the exploratory biomarker endpoint, N-terminal pro b-type natriuretic peptide, an indicator of cardiac response, was observed after 16 weeks with macitentan compared to placebo (95% CL: -32%, -6%; p=0.006) in the overall patient population. In addition, a 13% reduction in pulmonary vascular resistance index (PVRi) was observed after 16 weeks with macitentan compared to placebo (95% CL: -27%, 3%; p=0.102 ITT) in a hemodynamic sub-study of 39 patients (20 in the macitentan group and 19 in the placebo group). The  mean change from baseline to Week 16 in PVRi was a decrease of -409.8 dyn.sec/cm5/m2 in the macitentan group and an increase of 79.4 dyn.sec/cm5/m2 in the placebo group. The PVRi least-squares mean difference at Week 16 was -434.8 dyn.sec/cm5/m2 between macitentan and placebo (95% CL: -791.5, -78.0 m; p=0.018, ITT). Patients in the sub-study also showed an improvement in exercise capacity: the mean change in 6-MWD from baseline was an increase of 34.1 m in the macitentan group and 3.5 m in the placebo group. The 6-MWD least-squares mean difference at Week 16 was 24.9 m between macitentan and placebo (95% CL: -9.1, 59.0 m; p=0.146 ITT).

Guy Braunstein, Head of Global Clinical Development, commented: "We have seen encouraging results on multiple measures, particularly in the hemodynamic sub-study. Preliminary results from the open label extension of the study suggest that patients originally randomized to placebo and subsequently treated with macitentan showed an improvement in exercise capacity after 24 weeks. We must fully understand the results, in particular the reason for the large placebo effect, to know what might be changed so that we can deliver on our commitment to patients with Eisenmenger Syndrome."

The MAESTRO safety set comprised 226 patients, 114 patients in the macitentan group and 112 patients in the placebo group. Macitentan was well tolerated in this patient population, and safety was, in general, consistent with the known safety profile for macitentan from previous clinical studies. The most frequently reported adverse events that occurred with higher frequency on macitentan vs. placebo were headache (11.4% vs. 4.5%) and upper respiratory tract infection (9.6% vs. 6.3%). Seven (6.1%) patients on macitentan experienced a serious adverse event compared with two (1.8%) patients on placebo. Two patients (1.8%) in each group discontinued the study treatment due to an adverse event. During the course of the study, there was one death reported (respiratory failure), in a patient receiving macitentan.