Angiotensinogen is the sole precursor of angiotensin peptides and has a key role in the pathogenesis of hypertension. Zilebesiran, an investigational RNA interference therapeutic agent with a prolonged duration of action, inhibits hepatic angiotensinogen synthesis.
Zilebesiran is a small interfering RNA that silences hepatic AGT expression leading to a decrease in production of angiotensinogen protein and suppresses synthesis of angiotensin I, and angiotensin II, and consequent blood pressure lowering.
Dose-dependent decreases in serum angiotensinogen levels and 24-hour ambulatory blood pressure were sustained for up to 24 weeks after a single subcutaneous dose of zilebesiran of 200 mg or more; mild injection-site reactions were observed.