CAMBRIDGE, Mass.– Alnylam Pharmaceuticals, Inc. (Nasdaq: ALNY), the leading RNAi therapeutics company, today announced the first patient has been dosed in ZENITH (ZilebEsiraN CardIovascular OuTcome Study in Hypertension), a global Phase 3 cardiovascular outcomes trial evaluating zilebesiran as a potential biannual treatment to reduce the risk of major adverse cardiovascular events in patients with uncontrolled hypertension.
Zilebesiran is an investigational RNAi therapeutic designed to silence liver-expressed angiotensinogen (AGT), the most upstream precursor in the Renin-Angiotensin-Aldosterone System (RAAS), which regulates blood pressure and impacts cardiovascular and renal health. Administered as a subcutaneous injection twice per year, zilebesiran has the potential to provide sustained 24-hour blood pressure control for patients with high unmet need.
“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, M.D., Ph.D., 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.”
The ZENITH trial (NCT07181109) will enroll approximately 11,000 patients across 35 countries to evaluate zilebesiran (300 mg) administered every six months versus placebo in patients with uncontrolled hypertension who either have established cardiovascular disease or are at high risk despite being on two or more antihypertensives. The primary endpoint is reduction in the risk of cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, or heart failure events compared with placebo.
Under its global collaboration and license agreement with Roche, Alnylam has triggered a $300 million milestone payment with the initiation of the ZENITH trial.
The trial builds on results from the KARDIA Phase 2 clinical program, including data from KARDIA-3 (Cohort A) presented at the European Society of Cardiology Congress in Madrid this summer. Additional results from KARDIA-3 (Cohort B) will be presented at the American Heart Association Scientific Sessions 2025.
