Macitentan Meets Primary, Secondary Endpoints in Phase II Trial

Patients with chronic thromboembolic pulmonary hypertension (CTEPH) experienced a significant reduction in pulmonary vascular resistance and an increase in 6-minute walking distance after taking macitentan, an endothelin receptor antagonist originally approved for the treatment of pulmonary arterial hypertension (PAH).

Results were seen in the MERIT-1 clinical trial, which was led by Ardeschir Ghofrani (pictured), MD, professor of pulmonary vascular research at Justus Liebig University, Giessen, Germany, and head of the Pulmonary Hypertension Division at the University Hospital in Giessen.

“Macitentan is an endothelin receptor antagonist that’s well known to work well in patients with pulmonary arterial hypertension, but so far has not been investigated in patients with CTEPH," Ghofrani said.

CTEPH patients have limited treatment options, he added, with surgical intervention being most common in patients with proximal vascular disease. The other treatment choice is medical therapy with riociguat, a stimulator of the soluble guanylate cyclase.

“There’s no data on the use of other PAH specific medications, and there’s no information on combination therapies in patients with CTEPH,” Ghofrani said. “So there’s a lack of information and an unmet medical need for further treatments in this condition.”

The MERIT-1 clinical trial was a randomized, placebo-controlled, multicenter study that sought to fill that knowledge and treatment gap. The primary endpoint was the change in pulmonary vascular resistance at 16 weeks of treatment, and the secondary endpoint was change in 6-minute walking distance.

The study duration was 24 weeks. The primary endpoint was assessed at 16 weeks, and the secondary endpoint was assessed at the study’s close.

“Pulmonary vascular resistance at 16 weeks was significantly reduced in the macitentan arm as opposed to the placebo arm. The secondary endpoint — the change in 6-minute walking distance – improved by more than 30 meters after 24 weeks irrespective of whether patients were on background therapies. This was very encouraging,” Ghofrani said.

The MERIT-1 study will be followed by the MERIT-1 Open Label Extension (MERIT-2) study, he added. In this study, all the patients that were initially included in MERIT-1 would be transitioned to active drug, and those who received active drug from the beginning would still be prospectively followed up on.

“This will provide very important safety information long term,” Ghofrani said. “It will also provide another indication of efficacy, particularly for those patients who are transitioning from placebo to active therapy.”

Macitentan’s safety profile was corroborated with what was observed in previous studies of patients with PAH.

“With this drug, both of these side effects were shown not to be increased as opposed to placebo, which is very good news for our patients,” Ghofrani said.