NYMC Faculty Publications

Zilebesiran a Promising Antihypertensive Therapy Inhibiting Angiotensinogen Synthesis

Author Type(s)

Faculty

DOI

10.1097/CRD.0000000000000645

Journal Title

Cardiology in Review

First Page

279

Last Page

284

Document Type

Article

Publication Date

5-1-2025

Department

Medicine

Keywords

angiotensinogen, essential hypertension, RAAS, resistant hypertension, siRNA, Zilebesiran

Disciplines

Medicine and Health Sciences

Abstract

Systemic hypertension is one of the most common noncommunicable diseases globally, with over one billion people affected. Despite the widespread use of numerous antihypertensive drugs, it is estimated that only a fifth of diagnosed patients achieve adequate blood pressure control. For this reason, the pursuit for novel antihypertensive therapies is ongoing. Zilebesiran, an siRNA designed to target the liver, is the newest potential addition to the renin-angiotensin-aldosterone system-inhibiting drugs. This subcutaneous injection post-transcriptionally silences the AGT gene responsible for the synthesis of angiotensinogen. By preventing the progenitor protein of the renin-angiotensin-aldosterone system, zilebesiran blocks the downstream production of angiotensin II, which plays multiple roles in blood pressure elevation. Phase I clinical trials have demonstrated a dose-dependent negative relationship between zilebesiran and blood pressure/serum angiotensinogen levels—with sustained effects up to 6 months. Researchers also demonstrated a promising safety profile, as most of the adverse events were mild to moderate in nature. Phase II trials assessing efficacy and optimal dosing are currently underway, with a predicted completion by 2025.

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