Aprocitentan, targeting the endothelin pathway, offers a new approach for managing hypertension alongside existing medications.

The US Food and Drug Administration approved aprocitentan (Tryvio, Idorsia) for the treatment of hypertension, in combination with other antihypertensive drugs, to lower blood pressure in adults who are not adequately controlled on other drugs.

Aprocitentan is the first oral anti-hypertensive therapy that works via a new therapeutic pathway to be approved in almost 40 years, according to a release from Idorsia. The drug is expected to be available in the second half of 2024.

Aprocitentan is an endothelin receptor antagonist that inhibits the binding of endothelin (ET)-1 to ETA and ETB receptors. The effects of ET-1 bear many similarities with the pathophysiology of hypertension, and ET-1 is a major driver of aldosterone production. 

Until the approval of aprocitentan, no systemic antihypertensive medications targeted the ET pathway, as approved antihypertensive therapies focus on the regulation of salt and water (diuretics), antagonism of the renin–angiotensin–aldosterone system, reduction of influx of extracellular calcium into the cell (calcium channel blockers), sympatholytic activity (beta blockers, central alpha-agonist agents), or non-selective vasodilatory effects.

Aprocitentan was evaluated as a monotherapy in a phase 2 study in patients with hypertension, and as an add-on therapy in a phase 3 study called PRECISION in patients with confirmed resistant hypertension. In PRECISION, aprocitentan was well tolerated and superior to placebo in lowering blood pressure at week four, with a sustained effect at week 40.

Lowering blood pressure reduces the risk of fatal and non-fatal cardiovascular events, primarily strokes and myocardial infarctions. The recommended dosage of aprocitentan is 12.5 mg orally once daily, with or without food.