Macitentan (Opsumit) for the treatment of pulmonary arterial hypertension.
The endothelin pathway is a key pathway for the pathogenesis of pulmonary arterial hypertension (PAH). Antagonism of this pathway is recommended as initial therapy in low-risk patient with PAH to inhibit fibrosis, cell proliferation, and inflammation caused by endothelin. Prior to October 2013, ambrisentan, a selective ETA receptor antagonist and bosentan, a dual ETA/ETB antagonist, were the only currently available agents for PAH targeting the endothelin pathway. Based on the results of the SERAPHIN trial, macitentan (brand name Opsumit®), a new ETA/ETB antagonist, has been US FDA approved to delay disease progression and reduce hospitalizations for PAH. SERAPHIN is the first ERA trial to use an event-driven strategy with a composite primary end point of morbidity or mortality. Previous trials have focused on short-term outcomes, such as improved 6-min walk distance and WHO functional class.
Section of Heart Failure/Transplant and Pulmonary Hypertension, Allegheny General Hospital, 320 East North Avenue, Pittsburgh, PA 15212-4772, USA.
Megan
M
Clarke
Claire
C
Walter
Richa
R
Agarwal
Manreet
M
Kanwar
Raymond L
RL
Benza
D000959:Antihypertensive Agents / Q000627:therapeutic use; D017322:Clinical Trials, Phase II as Topic; D017326:Clinical Trials, Phase III as Topic; D065130:Endothelin A Receptor Antagonists / Q000627:therapeutic use*; D065627:Familial Primary Pulmonary Hypertension / Q000188:drug therapy*; D006801:Humans; D011743:Pyrimidines / Q000627:therapeutic use*; D013449:Sulfonamides / Q000627:therapeutic use*
D000959:Antihypertensive Agents; D065130:Endothelin A Receptor Antagonists; D011743:Pyrimidines; D013449:Sulfonamides; C533860:macitentan
drug development; endothelin; pharmacodynamics; pharmacokinetics; pulmonary arterial hypertension