Roche and Alnylam advance zilebesiran into global phase III cardiovascular outcomes trial for people with uncontrolled hypertension

Core Viewpoint - Roche and Alnylam are initiating a Phase III cardiovascular outcomes trial (CVOT) for zilebesiran, an RNAi therapeutic aimed at reducing major adverse cardiovascular events in patients with uncontrolled hypertension [1][5]. Group 1: Clinical Trial Details - The Phase III trial, named ZENITH, will enroll approximately 11,000 patients and evaluate zilebesiran (300 mg) administered every six months compared to placebo [5][16]. - The KARDIA-3 study demonstrated a placebo-adjusted reduction in office systolic blood pressure (SBP) of -5.0 mmHg at month three and -3.9 mmHg at month six for the 300 mg dose [2][12]. - KARDIA-3 identified a patient population that could benefit most from zilebesiran, particularly those on diuretics with a baseline SBP greater than 140 mmHg, showing reductions of -9.2 mmHg at month three and -8.3 mmHg at month six [3][12]. Group 2: Safety and Efficacy - Zilebesiran exhibited an encouraging safety profile, with serious adverse events occurring in 3.8% of patients treated with zilebesiran compared to 4.5% in the placebo group, and no deaths reported during the six-month period [14]. - The drug demonstrated clinically meaningful reductions in blood pressure and sustained effects over six months, indicating its potential as a long-acting therapy for hypertension [8][12]. Group 3: Market Need and Potential - Hypertension affects over 1.2 billion people globally, with up to 80% of patients not achieving adequate blood pressure control, highlighting the need for new treatment options [6][20]. - Zilebesiran's biannual dosing could address adherence issues associated with daily oral therapies, potentially reducing the risk of serious health complications and cardiovascular events [4][17].