Macitentan for the treatment of pulmonary arterial hypertension

Figures & data

Figure 1 Macitentan and its two metabolites.

Abbreviation: ACT, Actelion.

Figure 2 Heterodimerization of G-coupled protein ERA_A and ERA_B receptors required to initiate downstream second messaging.

Abbreviations: ERA, endothelin-receptor antagonist; ET, endothelin.

Table 1 Comparative features for FDA-approved ERAs

Comparators	Bosentan	Ambrisentan	Macitentan
Date of FDA approval	2001	2007	2013
Selectivity	Nonselective	Selective	Nonselective
Kb ratio*	0.7	1.0	6.3
Half-life	5 hours	15 hours	16 hours
Dosing	62.5 mg BID or 125 mg BID	5 mg QD or 10 mg QD	10 mg QD
Study outcomes	Primary outcome:	Primary outcome:	Composite primary end point:
	6MW distance	6MW distance	Death
	Secondary outcome:	Secondary outcome:	Lung transplantation
	WHO class	WHO class	Atrial septostomy
	Borg dyspnea index	Borg dyspnea index	Parenteral prostanoid initiation
	Time to clinical worsening	Time to clinical worsening	Worsening of PAH
		Plasma B-type natriuretic peptide	Secondary end points:
			6MW distance
			WHO class
			Hemodynamic end points:
			PVR reduction
			Cardiac index increase

Note:

* Functional inhibition constant.

Abbreviations: FDA, US Food and Drug Administration; ERA, endothelin-receptor antagonist; BID, bis in die (twice daily); QD, quaque die (every day); 6MW, 6-minute walk; WHO, World Health Organization; PAH, pulmonary arterial hypertension; PVR, pulmonary vascular resistance.

Table 2 Adverse-effect profile for FDA-approved ERAs

Adverse effects	Bosentan	Ambrisentan	Macitentan
Aminotransferase elevations	>10% of cases	<3% of cases	<3% of cases (subject of ongoing Phase IV evaluation)
Peripheral edema	3%–10% of cases	>10% of cases	<3% of cases
Anemia	3%–10% of cases	3%–10% of cases	3%–10% of cases

Abbreviations: FDA, US Food and Drug Administration; ERA, endothelin-receptor antagonist.