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Review Article
- Zilebesiran: an RNA therapeutic agent interfering with angiotensinogen synthesis
- Woong Gil Choi
- Cardiovasc Prev Pharmacother. 2025;7(3):102-108. Published online July 25, 2025
- DOI: https://doi.org/10.36011/cpp.2025.7.e12
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Abstract
PDF - Hypertension remains a leading modifiable risk factor for cardiovascular morbidity and mortality worldwide, yet rates of blood pressure control remain suboptimal despite the availability of multiple classes of antihypertensive agents. Zilebesiran is a novel small interfering RNA therapeutic that targets hepatic angiotensinogen messenger RNA, offering a unique upstream approach to renin-angiotensin-aldosterone system suppression. Conjugated with N-acetylgalactosamine for liver-specific delivery, zilebesiran enables sustained angiotensinogen silencing and long-lasting blood pressure reductions after a single subcutaneous injection. Preclinical studies have demonstrated potent antihypertensive effects with minimal toxicity. Phase 1 and 2 clinical trials (KARDIA-1 and KARDIA-2) confirmed its dose-dependent and durable efficacy, with significant 24-hour ambulatory systolic blood pressure reductions maintained for over 6 months. Zilebesiran also showed a favorable safety profile, with minimal adverse effects and no evidence of renal, hepatic, or electrolyte disturbances. Its long-acting mechanism, reduced dosing frequency, and potential to improve adherence make it a promising therapeutic candidate for both general and resistant hypertension. Ongoing phase 2b studies (KARDIA-3) will further clarify its utility in high-risk patients and those with chronic kidney disease.
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Citations
Citations to this article as recorded by
- Zilebesiran as an Innovative siRNA-Based Therapeutic Approach for Hypertension: Emerging Perspectives in Cardiovascular Medicine
Petruta A. Morosan, Amelian M. Bobu, Alexandru Carauleanu, Radu Popa, Claudia F. Costea, Cristiana Filip, Catalin M. Buzduga, Emilia Patrascanu, Andrei I. Cucu, Razvan I. Tudosa, Roxana Covali, Anca Haisan
International Journal of Molecular Sciences.2025; 26(21): 10717. CrossRef
- Zilebesiran as an Innovative siRNA-Based Therapeutic Approach for Hypertension: Emerging Perspectives in Cardiovascular Medicine
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