zilebesiran + amlodipine

A combination of **zilebesiran** and **amlodipine** under investigation for the management of hypertension. Zilebesiran is a small interfering RNA (siRNA) therapeutic that targets hepatic angiotensinogen (AGT) mRNA to suppress angiotensinogen synthesis, thereby decreasing angiotensin II levels and disrupting the renin–angiotensin–aldosterone system (RAAS)[1][4][6]. This results in reduced blood pressure through a novel gene-silencing approach with potential for infrequent (e.g., biannual) dosing[4][6]. Amlodipine is a dihydropyridine calcium channel blocker that reduces blood pressure by inhibiting calcium influx into vascular smooth muscle, causing peripheral vasodilation[2]. Clinical trials (e.g., KARDIA-2) demonstrate that the combination achieves additive reductions in systolic blood pressure compared to either agent alone, especially when zilebesiran is added to chronic amlodipine therapy, with sustained efficacy up to six months[3][5][7]. This combination is under investigation for treating primary hypertension in adults with inadequate blood pressure control on standard therapy[1][3][7].