Zilebesiran Fails to Substantially Lower Blood Pressure in Late-Breaking Trial
MADRID – A highly anticipated trial of zilebesiran, an investigational RNA interference therapy, showed no statistically significant reduction in blood pressure compared with placebo, researchers announced at the European Society of cardiology Congress. The findings, presented August 29, 2025, represent a setback for the potential treatment of hypertension and raise questions about the role of siRNA-based therapies in blood pressure management.
The results impact the millions worldwide living with uncontrolled hypertension and the search for novel treatment approaches beyond traditional medications. While zilebesiran demonstrated substantial reductions in levels of angiotensinogen, a key driver of the renin-angiotensin-aldosterone system, these reductions did not translate into clinically meaningful blood pressure lowering. The study’s outcome will likely prompt a reassessment of zilebesiran’s development pathway and potentially influence investment in similar RNA interference programs targeting hypertension.
The trial, led by Nalini Pagidipati, assessed the efficacy and safety of zilebesiran in patients with essential hypertension whose blood pressure remained inadequately controlled despite treatment with three or more antihypertensive medications.
Source: pagidipati N, et al. hot line 4. Presented at: European Society of Cardiology Congress; Aug. 29-Sept. 1, 2025; Madrid (hybrid meeting).
Disclosures: The study was funded by Alnylam. Pagidipati reports receiving research support from Alnylam,Amgen,Bayer,Boehringer ingelheim,Eli Lilly,Merck,Novartis and Novo Nordisk; and consulting and/or serving on advisory panels for Alnylam,Amgen,AstraZeneca,Bayer,Boehringer Ingelheim,Corcept,corsera,Eli Lilly,Esperion,Merck,NewAmsterdam Pharma,Novartis and Novo Nordisk.
