Roche and Alnylam are initiating a Phase III trial for zilebesiran, an RNAi therapeutic for hypertension. This decision is supported by data from the KARDIA Phase II program, including KARDIA-3. The KARDIA-3 study, presented at the European Society of Cardiology Congress 2025, showed clinically meaningful reductions in office systolic blood pressure at three months with continuous control through six months with a 300 mg dose of zilebesiran. No additional benefit was seen with a 600 mg dose. While KARDIA-3 did not meet pre-specified statistical significance due to multiplicity testing, it identified a patient population that could benefit most. The study also demonstrated encouraging safety when zilebesiran was combined with other antihypertensives. Specifically, a subgroup analysis of patients on diuretics showed greater blood pressure reductions. Zilebesiran targets angiotensinogen, potentially offering durable blood pressure control with twice-yearly subcutaneous dosing. The upcoming Phase III ZENITH trial will evaluate zilebesiran's ability to reduce major adverse cardiovascular events in approximately 11,000 patients with uncontrolled hypertension. Hypertension affects over 1.2 billion people globally, with up to 80% not achieving adequate blood pressure control. Poor adherence to daily medications contributes significantly to this issue.