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Actelion’s PAH drug fails to meet primary objective in Phase III study

PBR Staff Writer Published 24 January 2017

A Phase III study evaluating Actelion's macitentan in patients with pulmonary arterial hypertension (PAH) due to Eisenmenger Syndrome failed to meet its primary goal.

The trial, Maestro, had enrolled 226 patients, with 135 of them in Functional Class II and was randomized in a 1:1 ratio. While one patient group was subjected to daily once 10 mg macitentan, the other group was given placebo.

Post 16 weeks of treatment, the mean change in 6-minute walk distance (6-MWD) from baseline was registered to have increased by 18.3m in the macitentan group in comparison to the 19.7m in the placebo group.

At week 16, the 6-MWD least-squares mean difference was calculated as -4.7 m between macitentan and placebo.

Also after 16 weeks with macitentan in comparison to placebo, a decrease by 20% was observed in the levels of N-terminal pro b-type natriuretic peptide which was the exploratory biomarker endpoint of the trial and also an indicator of cardiac response.

Additionally, a hemodynamic sub-study of 39 patients showed that after 16 weeks, there was a 13% decrease in pulmonary vascular resistance index (PVRi) with macitentan when compared to placebo.

Actelion global clinical development head Guy Braunstein said: "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."

Opsumit (macitentan), an orally available endothelin receptor antagonist, resulted from a drug discovery process in Actelion's laboratories.

In the US, Opsumit is indicated to treat PAH, WHO Group I to delay disease progression.