Macitentan (Opsumit®) is an orally available endothelin receptor antagonist (ERA) that resulted from a tailored drug discovery process in Actelion’s laboratories, which is currently approved for the treatment of pulmonary arterial hypertension (PAH), a chronic, life-threatening disorder which severely compromises the function of the lungs and heart.
Macitentan is currently being studied in the Phase III study MAESTRO (MAcitentan in Eisenmenger Syndrome To RestOre exercise capacity). A multi-center, double-blind, randomized, placebo-controlled, parallel-group, Phase 3 study to evaluate the effects of macitentan on exercise capacity in subjects with Eisenmenger Syndrome.
This study is ongoing with approximately 220 subjects to be randomized in a 1:1 ratio into 2 treatment groups (macitentan 10mg or placebo) over a 16 week treatment period.
Macitentan is currently being evaluated in patients with chronic thromboembolic pulmonary hypertension (CTEPH) in the Phase II study MERIT (Macitentan in thE tReatment of Inoperable chronic Thromboembolic pulmonary hypertension). MERIT is a prospective, randomized, placebo-controlled, double-blind, multicenter, parallel-group study to assess the efficacy, safety and tolerability of 10mg macitentan in subjects with inoperable CTEPH.
At the end of 2015, the initial results of the Phase II MELODY study with macitentan became available. MELODY was a prospective, multicenter, double-blind, randomized, placebo-controlled, parallel-group, 12-week study to evaluate the safety and tolerability of Macitentan in subjects with combined prE- and post-capiLlary pulmOnary hypertension (CpcPH) due to left ventricular DYsfunction. In the exploratory Phase II study, macitentan was generally well tolerated in this Group 2 pulmonary hypertension patient population with heart failure. In addition, encouraging hemodynamic effects were observed. The company will now fully evaluate the data and, together with the results of the current Phase II study with a new endothelin receptor antagonist (ERA), make a decision on the future development strategy of Actelion's ERAs beyond PAH.
Macitentan has been studied in SERAPHIN, a multicenter, double-blind, placebo-controlled, parallel-group, event-driven, Phase III outcome study in 742 patients with symptomatic PAH, who were randomized to three treatment groups (placebo [N = 250], 3 mg [N = 250] or 10 mg [N = 242] of macitentan once daily), to assess the long-term effect on morbidity or mortality.
Treatment with macitentan 10 mg resulted in a 45% risk reduction (hazard ratio [HR] 0.55; 97.5% CI: 0.39 to 0.76; logrank p < 0.0001) of the composite morbidity-mortality endpoint up to EOT when compared to placebo. The treatment effect was established early and was sustained. In patients already on background therapy for PAH treatment with macitentan 10mg resulted in a 38% risk reduction (HR 0.62; 97.5% CI: 0.43 to 0.8; logrank p=0.0094) of the composite morbidity-mortality endpoint compared to placebo.
The risk of PAH related death or hospitalization for PAH up to EOT was reduced by 50% (HR 0.50; 97.5% CI: 0.34 to 0.75; logrank p < 0.0001) in patients receiving macitentan 10 mg (50 events) compared to placebo.
Efficacy of macitentan 10 mg on the primary endpoint was consistent across subgroups of age, sex, ethnic origin, geographical region, aetiology, by monotherapy or in combination with another PAH therapy and by WHO FC (I/II and III/IV).
The most commonly reported adverse drug reactions are nasopharyngitis (14.0%), headache (13.6%) and anaemia (13.2%, see section 4.4). The majority of adverse reactions are mild to moderate in intensity.
2013 – Opsumit approved by the EU Commission
2013 – Opsumit approved by the US FDA
2012 – SERAPHIN outcome study meets its primary endpoint
2007 – Initiation of Phase III SERAPHIN study in PAH patients
2005 – Initiation of Phase II dose ranging study
2004 – Entry-into-man
2003 – Selection of macitentan for initiation of preclinical studies
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