CardioExchange Archive

Actelion has announced positive top-line results for a phase III trial of a new oral drug for the treatment of pulmonary arterial hypertension (PAH). The drug, selexipag, is a first-in-class orally available selective prostacyclin IP receptor agonist.

The pivotal, double-blind GRIPHON study was the largest outcome trial ever performed in PAH. A total of 1,156 PAH patients were randomized to selexipag or placebo. The company said that trial had “met its primary efficacy endpoint with high statistical significance.” After followup of up to 4.3 years, selexipag reduced the risk of a morbidity or mortality event by 39% (p<0.0001). The results were consistent across the key subgroups of age, gender, WHO functional class, PAH etiology, and background therapy. Endpoint events were adjudicated by a blinded independent committee.

Actelion reported that 14% of patients in the selexipag group and 7% of patients in the placebo group discontinued treatment due to adverse events. The most common adverse events associated with selexapig were similar to those seen with previous prostacyclin therapies, including headache, diarrhea, nausea, jaw pain, vomiting, pain in extremity, myalgia, nasopharyngitis, and flushing.

Most patients in the study were taking other oral PAH drugs at the start of the study.

“I have been prescribing intravenous prostacyclin therapies in PAH patients for almost twenty years. Today’s GRIPHON results represent a major step forward. For the first time, with selexipag, we have an oral compound acting on the prostacyclin pathway showing a significant risk reduction on a highly clinically relevant endpoint,” said Gérald Simonneau, a member of the trial’s steering committee, in the Actelion press release.

John Ryan, an expert on PAH at the University of Utah, expressed enthusiasm for the news:

This is an exciting trial and an intriguing result, especially when considering the size of the study, the prolonged follow-up, and the high percentage of patients already on background therapy. Having an oral agent in PAH that significantly impacted mortality/morbidity represents a major step forward and could be a real game changer in this aggressive and fatal disease.”