Zilebesiran: A Breakthrough in Hypertension Management with Biannual Dosing and Favorable Safety Profile

Dear Sir, Hypertension is a considerable cause of morbidity and mortality across the globe. It is estimated to contribute either directly or indirectly to one out of every eight deaths worldwide, accounting for 57 million disability-adjusted life years (DALYs) or 3.7% of the total.1 It is directly linked to coronary artery disease, heart failure, stroke, and renal insufficiency, among other life-threatening diseases. Hypertensive complications frequently arise in people older than 50 and one of the most contributing factors in that age group is noncompliance to antihypertensive medications. Polypharmacy, particularly in elderly patients with comorbidity predisposes them to further health concerns due to multiple dozing, drug-to-drug, and drug-to-food interactions.2 Zilebesiran, an interference RNA, is a promising drug therapeutically designed to specifically target to halt the synthesis of angiotensinogen, which is the precursor of angiotensin peptides and a vital regulator of arterial blood pressure. Zilebesiran demonstrates a notable selectivity towards hepatic glycoprotein receptors and effectively causes a reduction in the production of hepatic angiotensinogen messenger RNA levels, Consequently, the hepatic production of angiotensinogen is markedly diminished.3 Previously, in a 2023 phase 1 study, Desai et al. reported a dose-dependent decrease in levels of serum angiotensinogen levels as well as blood pressure levels after receiving a single subcutaneous shot of Zilebesiran and the effects were retained for up to 24 weeks.4 Recently, a February 2024 study published in the Journal of American Medical Association complemented the findings of the previous studies and demonstrated a 3-month change in the average systolic blood pressure of 9.1 mmHg (P < 0.001) from baseline in the group treated with 300 mg Zilebesiran subcutaneously once every 6 months. Serious adverse drug reactions were also observed with less frequency in patients treated with Zilebesiran (11 out of 306 patients or 3.6%) compared with those treated with a placebo (5 out of 75 patients or 6.7%).5 Zilebesiran is an innovative drug that addresses challenges associated with polypharmacy and compliance in both elderly and young patients in today's fast-paced world. Zilebesiran revolutionizes hypertension management by offering a hassle-free approach with its biannual dosing ensuring control of blood pressure levels for up to 6 months. Ongoing clinical trials are currently assessing the long-term efficacy of Zilebesiran and determining the optimal dosing regimen. Financial support and sponsorship Nil. Conflicts of interest There are no conflicts of interest.