Switzerland-based Actelion Pharmaceuticals' initial analysis indicates that the pivotal, long-term phase III SERAPHIN study with macitentan, a novel dual endothelin receptor antagonist, has met its primary endpoint.
In the multinational, multi-center, event-driven study, 742 patients suffering from pulmonary arterial hypertension (PAH) were treated with macitentan 3mg, 10mg or placebo for up to three and a half years. Mean exposure to study treatment was 85.3 weeks for placebo patients (n=249), 99.5 weeks for patients on 3mg (n=250) and 103.9 weeks for patients on 10mg (n=242).
Results show that macitentan, at both the 3mg and 10mg dose, decreased the risk of a morbidity/mortality event over the treatment period versus placebo. This risk was reduced by 45% in the 10mg dose group (p
Secondary efficacy endpoints, including change from baseline to month six in six-minute walk-distance, change from baseline to month six in WHO functional class and time—over the whole treatment period—to either death due to PAH or hospitalization due to PAH, also showed a dose-dependent effect (p
"I am extremely pleased with the outstanding SERAPHIN results,” said Jean-Paul Clozel, CEO of Actelion. “Submission of the registration dossier to Health Authorities worldwide is expected by the fourth quarter of 2012.”
Macitentan was well tolerated in this patient population. The number of adverse events reported and patients discontinuing treatment due to adverse events was similar across all groups. Elevations of liver alanine or aspartate aminotransferases greater than three times the upper limit of normal were observed in 4.5% of patients receiving placebo, in 3.6% of patients on 3mg of macitentan and in 3.4% of patients on 10mg of macitentan. In addition, no difference was observed between macitentan and placebo on fluid retention (edema). A decrease in hemoglobin was observed more frequently on macitentan than placebo, with no difference in treatment discontinuation between groups.