Genentech and Alnylam Initiate Phase III Trial for Zilebesiran in Hypertension Patients

What's Happening?

Genentech and Alnylam have announced the initiation of a Phase III cardiovascular outcomes trial for zilebesiran, an RNAi therapeutic aimed at reducing major adverse cardiovascular events in patients with uncontrolled hypertension. This decision follows promising results from the KARDIA Phase II program, which demonstrated zilebesiran's ability to lower systolic blood pressure in patients with high cardiovascular risk. The Phase III trial, named ZENITH, will enroll approximately 11,000 patients globally and evaluate the efficacy of zilebesiran administered biannually. The trial aims to address the unmet need for effective long-term blood pressure control, as current treatments fail to adequately manage hypertension in up to 80% of patients.

Why It's Important?

Hypertension is a leading modifiable risk factor for cardiovascular disease, affecting one in three adults worldwide. Despite the availability of antihypertensive medications, many patients struggle to maintain target blood pressure levels, increasing their risk of cardiovascular events. Zilebesiran offers a potential solution with its long-acting, twice-yearly dosing regimen, which could improve adherence and provide continuous blood pressure control. If successful, this therapeutic could significantly reduce the burden of cardiovascular disease, which is responsible for millions of deaths annually. The trial's outcome could influence future treatment protocols and healthcare strategies for managing hypertension.

What's Next?

The ZENITH Phase III trial is expected to begin by the end of 2025, pending regulatory approval. It will focus on patients with uncontrolled hypertension who are already on multiple antihypertensive medications. The trial will assess zilebesiran's impact on reducing cardiovascular death, nonfatal myocardial infarction, stroke, and heart failure events compared to placebo. The results could pave the way for zilebesiran's approval and integration into standard hypertension treatment regimens, potentially transforming patient care and outcomes in this high-risk population.