Macitentan: Phase III data

The double-blind, international Phase III SERAPHIN trial in 742 patients with symptomatic PAH showed that once-daily 3 and 10 mg oral macitentan each met the primary endpoint of reducing a composite of time to first morbidity or mortality event vs. placebo. Specifically, low- and high-dose macitentan reduced the risk of a morbidity or mortality event, defined as death, atrial septostomy, initiation of IV or subcutaneous prostanoids, lung transplantation or other worsening of PAH, by 30% and 45%, respectively, compared to placebo (p=0.0108 and p<0.0001). Other worsening of PAH was defined as >=15% reduction in 6MWD, the need for new PAH treatment and worsening of PAH symptoms, including either an increase in WHO functional class or appearance or worsening of right heart failure symptoms.

On secondary endpoints, macitentan dose-dependently and significantly improved 6MWD and WHO functional class from baseline to 6 months and reduced time over the whole treatment period to either death due to PAH or hospitalization due to PAH vs. placebo (p<0.05 for all). Neither dose of macitentan significantly improved all-cause mortality vs. placebo. Macitentan was well tolerated with a similar number of adverse events and discontinuations due to adverse events reported across all treatment groups. Reductions in hemoglobin were observed more frequently in patients receiving macitentan vs. placebo. Furthermore, elevations of liver alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels that were >3 times the upper limit of normal were observed in 4.5%, 3.6% and 3.4% of patients receiving placebo, low-dose macitentan and high-dose macitentan, respectively. ...