Cardiology Letters 2024, 33(5):338-343

Zilebesiran - a new principle and new hope in the treatment of hypertension

Juraj Dúbrava

Oddelenia neinvazívnej kardiológie, Univerzitná nemocnica Bratislava, Slovenská republika

Blood pressure control in arterial hypertension is unsatisfactory and up to half of patients do not achieve the targets. A natural consequence is research for new classes of antihypertensive drugs. Zilebesiran is an experimental small-interfering RNA (siRNA) therapeutic. It is designed to intervene selectively in the liver, where it causes post-transcriptional silencing of the gene responsible for the synthesis of angiotensinogen. Zilebesiran thus inhibits the renin-angiotensin-aldosterone system at its very beginning. The extrahepatic expression of angiotensinogen is preserved, limiting off-target effects on the kidneys and other tissues. Zilebesiran is the first siRNA with a proven positive effect in hypertension in humans. In phase 1 and 2 clinical trials in adults with mild and moderate hypertension a dose-dependent decrease in serum angiotensinogen levels (> 90%) and 24-hour systolic blood pressure (> 10 mmHg at doses ≥ 200 mg) were sustained 6 months after a single s.c. application. The safety profile of zilebesiran was favorable, with no reduction in renal function. The advantage is a very long interval between applications (6 months), and therefore zilebesiran can be an effective weapon against non-adherence.

Keywords: zilebesiran; siRNA; arterial hypertension; blood pressure

Published: May 1, 2024  Show citation