Roche and Alnylam will conduct a Phase III trial to test zilebesiran’s ability to reduce cardiovascular risk in patients with uncontrolled hypertension, based on data from the KARDIA program. The Phase II KARDIA-3 study showed zilebesiran lowered blood pressure significantly at month three and maintained control at month six. The study highlighted the potential benefits of combining zilebesiran with a diuretic. Zilebesiran demonstrated promising safety when used alongside multiple background therapies. The upcoming ZENITH trial, expected to begin in 2025, will enroll 11,000 patients to further evaluate zilebesiran’s effectiveness in reducing cardiovascular events in hypertensive patients. Zilebesiran, a potential best-in-disease RNAi anti-hypertensive, showed clinically meaningful reductions in office systolic blood pressure in the Phase II KARDIA-3 study, with continuous control through month six. A Phase III cardiovascular outcomes trial is expected to start by year-end. In Cohort A, zilebesiran 300 mg achieved significant reductions in office SBP at month three compared to placebo, with sustained benefits at month six. The drug demonstrated an encouraging safety profile when combined with two or more antihypertensives. Results from KARDIA-3 Cohort B are awaited. The global ZENITH CVOT will assess zilebesiran’s impact on reducing cardiovascular events in patients with uncontrolled hypertension and established or high risk for CVD. In a Phase III trial, zilebesiran showed significant reductions in blood pressure from a comprehensive KARDIA data set gathered from Phase II studies. This RNAi anti-hypertensive, given twice-yearly, displayed promising safety when combined with multiple antihypertensives. A Phase III cardiovascular outcomes trial is set to launch later this year. Cardiovascular disease is a major global health concern, with hypertension as a leading modifiable risk factor. Despite available treatments, many patients struggle to reach and maintain blood pressure targets, highlighting the need for innovative approaches like RNAi therapeutics. Founded in 1896, Roche focuses on developing medicines and diagnostics to improve global healthcare, with a commitment to sustainability and scientific excellence.

Read more at Phase III trial informed by comprehensive KARDIA data set shows zilebesiran’s effectiveness in reducing blood pressure, with potential for twice-yearly dosing. Presented at the European Society of Cardiology Congress 2025. Cardiovascular outcomes trial to start by year-end. (GlobeNewswire): Roche and Alnylam advance zilebesiran into global phase III