Alnylam Presents Phase 2 Safety Data for Zilebesiran

Alnylam presented pooled Phase 2 safety data for zilebesiran, an investigational RNAi therapeutic being evaluated for cardiovascular risk reduction in patients with hypertension, with the potential to provide continuous control of blood pressure. The results support continued evaluation of zilebesiran in patients with hypertension and high CV risk in ZENITH, a global Phase 3 Cardiovascular Outcomes Trial that was initiated in September 2025. Building on the efficacy and safety results of the KARDIA Phase 2 program, these data reinforce the rationale for evaluating zilebesiran in patients with hypertension and established or at high risk of CVD, despite the use of at least two or more antihypertensives, in ZENITH. By targeting liver-expressed angiotensinogen, the most upstream precursor in the renin-angiotensin-aldosterone system, zilebesiran has the potential to provide continuous control of blood pressure with biannual dosing, offering a potentially differentiated approach to hypertension and CV risk management in patients with the highest unmet need. Pooled Safety Analysis from Phase 2 Studies A comprehensive analysis of safety across the Phase 2 KARDIA program demonstrated an acceptable safety profile for zilebesiran, both as monotherapy and in combination with standard-of-care antihypertensives, across patients with mild-to-moderate hypertension, those at high CV risk, or with lower eGFR at baseline. In the analysis, clinically relevant safety events, such as hypotension, hyperkalemia, and eGFR decline, were low across the patient populations, including those receiving zilebesiran in combination with an angiotensin-converting enzyme inhibitor or an angiotensin II receptor blocker. As previously reported, the majority of these events were transient and resolved without intervention.