Therapeutic advances in respiratory disease
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Ther Adv Respir Dis · Jun 2014
The potential for macitentan, a new dual endothelin receptor antagonist, in the treatment of pulmonary arterial hypertension.
In recent years in the management of pulmonary arterial hypertension (PAH), endothelin receptor antagonists (ERAs) represent a well-established class of therapeutic agents with clear beneficial effects. Macitentan (Opsumit®), a dual ERA optimized for efficacy and safety, is the newest drug in the class. Macitentan presents a number of key beneficial characteristics, including increased in vivo preclinical efficacy versus existing ERAs, resulting from sustained receptor binding and physicochemical properties that allow enhanced tissue penetration. ⋯ In the SERAPHIN trial, a phase III long-term study of PAH, macitentan significantly reduced morbidity and mortality by 45% versus placebo, providing sustained long-term improvements in exercise capacity. No association was found between changes in exercise capacity and long-term clinical outcomes, but improved cardiopulmonary hemodynamics were recorded in macitentan-treated patients irrespective of baseline background PAH therapy or World Health Organization functional class. Based on these favorable data, the US Food and Drug Administration approved the 10 mg/day dose in late 2013 and the same process has recently been concluded by the European Medicines Agency.