General Information

Opsumit (macitentan) is a tissue-targeting Endothelin Receptor Antagonist. Endothelin Receptor Antagonists mediate a variety of deleterious effects, such as vasoconstriction, fibrosis, proliferation, hypertrophy, and inflammation.

Opsumit is specifically indicated for the treatment of pulmonary arterial hypertension (WHO Group I) to delay disease progression.

Opsumit is supplied as a tablet for oral administration. The recommended dose is 10 mg once daily.

Mechanism of Action

Opsumit (macitentan) is a tissue-targeting Endothelin Receptor Antagonist. Endothelin Receptor Antagonists mediate a variety of deleterious effects, such as vasoconstriction, fibrosis, proliferation, hypertrophy, and inflammation. Macitentan is an endothelin receptor antagonist that prevents the binding of ET-1 to both ETA and ETB receptors. Macitentan displays high affinity and sustained occupancy of the ET receptors in human pulmonary arterial smooth muscle cells. One of the metabolites of macitentan is also pharmacologically active at the ET receptors and is estimated to be about 20% as potent as the parent drug in vitro.

Side Effects

Adverse events associated with the use of Opsumit may include, but are not limited to, the following:

• anemia
• nasopharyngitis/pharyngitis
• bronchitis
• headache
• influenza
• urinary tract infection

Clinical Trial Results

The FDA approval of Opsumit was based on a multi-center, long-term (average duration of exposure approximately 2 years), placebo-controlled study in 742 subjects with symptomatic [WHO functional class (FC) II-IV] PAH who were randomized to placebo, 3 mg macitentan or 10 mg macitentan once daily. The primary study endpoint was time to the first occurrence of death, a significant morbidity event, defined as atrial septostomy, lung transplantation, initiation of IV or subcutaneous (SC) prostanoids, or other worsening of PAH during double-blind treatment plus 7 days. Treatment with Opsumit 10 mg resulted in a 45% reduction (p<0.0001) in the occurrence of the primary endpoint up to end of double-blind treatment compared to placebo.