zilebesiran + irbesartan

**Zilebesiran + irbesartan** is an investigational fixed-dose combination of two antihypertensive agents under clinical investigation for the treatment of hypertension. **Zilebesiran** is a subcutaneously administered RNA interference (RNAi) therapeutic that targets hepatic angiotensinogen synthesis, reducing levels of angiotensin II and thus lowering blood pressure. It acts via a small interfering RNA (siRNA) mechanism, delivered to the liver via GalNAc conjugation for hepatocyte specificity, leading to prolonged angiotensinogen inhibition and durable blood pressure reduction. **Irbesartan** is a well-established oral small molecule angiotensin receptor blocker (ARB) that selectively antagonizes the type 1 angiotensin II receptor (AT1), resulting in vascular smooth muscle relaxation and decreased aldosterone secretion, further lowering blood pressure. Combination therapy with zilebesiran and irbesartan demonstrates additive blood pressure lowering effects, with each drug acting on different components of the renin-angiotensin-aldosterone system (RAAS) for enhanced efficacy. Zilebesiran is being developed by Alnylam for sustained antihypertensive effects with infrequent dosing; irbesartan is marketed by several companies as a generic agent and has long-standing approvals for hypertension and nephropathy. Zilebesiran + irbesartan is currently being studied in phase 1 and phase 2 trials for hypertension[1][3][4][5][6][7].

Other names

zilebesiran and irbesartan co-administration