MAESTRO study of Opsumit (macitentan) in patients with pulmonary arterial hypertension fails to meet primary objective- Actelion

Actelion has announced that the MAESTRO study to assess the efficacy, safety and tolerability of Opsumit (macitentan) in patients with pulmonary arterial hypertension (PAH) due to Eisenmenger Syndrome did not meet its primary objective. After 16 weeks of treatment, the mean change in 6-minute walk distance (6-MWD) from baseline was an increase of 18.3 meters in the macitentan group and 19.7 m in the placebo group. The 6-MWD least-squares mean difference at Week 16 was -4.7 m between macitentan and placebo.

In the per-protocol population (200 patients), the mean change in 6-MWD from baseline was an increase of 30.2 m in the macitentan group and 18.9 m in the placebo group. The 6-MWD least-squares mean difference at Week 16 was 6.4 m between macitentan and placebo. 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 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 in a hemodynamic sub-study of 39 patients (20 in the macitentan group and 19 in the placebo group).

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. 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%). The company will now fully analyze the data and make them available through a peer-reviewed publication.