Alnylam has dosed the first patient in ZENITH, its global Phase 3 cardiovascular outcomes trial of the investigational therapy zilebesiran for patients with uncontrolled hypertension, the company said.
The trial—which is being conducted in collaboration with Roche—will enroll about 11,000 patients across 35 countries. It will compare twice-annual 300 mg subcutaneous doses of zilebesiran versus placebo in hypertensive patients who already receive two or more antihypertensive agents and who have either established cardiovascular disease or are at high cardiovascular risk despite treatment, according to the company.
The primary endpoint is a composite one: cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, or heart failure events (including hospitalization or urgent visits).
Zilebesiran is a small interfering RNA (siRNA) therapeutic designed to suppress liver-derived angiotensinogen (AGT), a precursor in the renin-angiotensin-aldosterone system, thereby regulating blood pressure, the company claims. Dosing every six months is enabled by Alnylam’s GalNAc-conjugate RNAi technology.
Earlier, in August, Alnylam had presented data from its Phase 2 KARDIA-3 (Cohort A) study; results from Cohort B are expected to be presented at the 2025 American Heart Association Scientific Sessions, the company said.
Regulatory approvals for zilebesiran have not yet been granted by agencies such as the FDA or EMA. Alnylam forwards that actual clinical outcomes may differ from expectations.
