Alnylam Pharmaceuticals, Inc. (NASDAQ:ALNY), the leading RNAi therapeutics company, today announced that the first patient has been dosed in ZENITH (ZilebEsiraN CardIovascular OuTcome Study in Hypertension), a global Phase 3 cardiovascular outcomes trial (CVOT) designed to evaluate the potential of zilebesiran, an investigational biannual subcutaneously administered RNAi therapeutic, to reduce the risk of major adverse cardiovascular (CV) events in patients with uncontrolled hypertension. Zilebesiran works by targeting liver-expressed angiotensinogen (AGT), the most upstream precursor in the Renin-Angiotensin-Aldosterone System (RAAS), which plays a key role in blood pressure regulation and impacts CV and renal health.

"The first patient dosed in our pivotal global Phase 3 cardiovascular outcomes trial, ZENITH, marks a major milestone in our commitment to exploring the ability of zilebesiran to reduce cardiovascular risk in patients with uncontrolled hypertension, a leading addressable cause of cardiovascular morbidity and mortality worldwide," said Weinong Guo, MD, PhD, Senior Vice President, Clinical Research at Alnylam. "By targeting the most upstream precursor of the RAAS, zilebesiran offers the potential for sustained, 24-hour, continuous control of blood pressure with biannual dosing in patients with high unmet need. It is one of the many novel RNAi therapeutics in our pipeline that demonstrates our long-term commitment to transforming the treatment of cardiovascular disease and improving outcomes for patients."

In this global multi-center Phase 3 ZENITH CVOT (NCT07181109), Alnylam and its partner Roche will enroll approximately 11,000 patients in 35 countries to evaluate zilebesiran (300 mg) administered every six months compared to placebo in patients with uncontrolled hypertension with either established CV disease or at high risk for CV disease despite the use of at least two or more antihypertensives. The primary objective will be to assess the impact of zilebesiran on reducing the risk of CV death, nonfatal myocardial infarction, nonfatal stroke, or heart failure (HF) events (hospitalization for HF or urgent HF visit), compared to placebo.

In August, Alnylam presented data from KARDIA-3 (Cohort A), the final study in the comprehensive KARDIA Phase 2 clinical program, as a late-breaking abstract at the European Society of Cardiology (ESC) Congress in Madrid, Spain. For additional details on the KARDIA-3 Cohort A presentation, please visit Capella. Results from KARDIA-3 Cohort B will be presented at the American Heart Association (AHA) Scientific Sessions 2025.