Zilebesiran, a siRNA targeting hepatic angiotensinogen, reduces blood pressure by up to 20 mmHg with effects lasting 24 weeks, offering potential for bi-annual dosing.
Does zilebesiran reduce blood pressure in hypertensive patients?
Zilebesiran, an siRNA targeting hepatic angiotensinogen, offers a promising approach for hypertension management with potential bi-annual dosing that could improve medication adherence and 24-hour blood pressure control.
INTRODUCTION: Hypertension is the main global risk factor for cardiovascular disease. Despite this, less than half of treated hypertensive patients are controlled. One reason for this is nonadherence, a major unmet need in hypertension pharmacotherapy. Small interfering RNA (small interfering ribonucleic acid) therapies inhibit protein translation, and, when linked to N-acetylgalactosamine, allow liver-specific targeting, and durability over several months. Targeted knockdown of hepatic angiotensinogen, the source of all angiotensins, offers a precision medicine approach. AREAS COVERED: This article describes the molecular basis for durability over months and the 24-h tonic target inhibition observed after one administration. We present an analysis of the published phase I trials using zilebesiran, a siRNA targeting hepatic angiotensinogen, which reduces blood pressure (BP) by up to 20 mmHg, lasting 24 weeks. Finally, we examine data evaluating reversibility of angiotensinogen knockdown and its relevance to the future clinical utility of zilebesiran. EXPERT OPINION: Further studies should assess safety, efficacy, and outcomes in larger, more broadly representative groups. An advantage of zilebesiran is the potential for bi-annual dosing, thereby reducing nonadherence and improving control rates. It may also reduce nighttime BP due to 24-h tonic control. The provision of adherence assessment services will maximize the clinical value of zilebesiran.
Addison et al. (Sat,) conducted a review in Hypertension. zilebesiran was evaluated on blood pressure (BP). Zilebesiran, a siRNA targeting hepatic angiotensinogen, reduces blood pressure by up to 20 mmHg with effects lasting 24 weeks, offering potential for bi-annual dosing.