Alnylam, Roche Advance Hypertension Drug to Pivotal Phase 3 Trial
Zilebesiran, a twice-yearly injection, will be tested in 11,000 high-risk patients following promising mid-stage results.
Alnylam Pharmaceuticals and its partner Roche are advancing their novel hypertension treatment, zilebesiran, into a large-scale global Phase 3 trial, a critical step toward potential approval. The decision follows positive Phase 2 data showing the RNA-based therapy can significantly reduce blood pressure in patients with uncontrolled hypertension.
The upcoming trial, named ZENITH, is set to enroll approximately 11,000 patients with high cardiovascular risk by the end of 2025. It will evaluate whether the blood pressure-lowering effects of the twice-yearly injection can lead to a meaningful reduction in major adverse events such as heart attacks and strokes.
This move was prompted by results from the comprehensive KARDIA Phase 2 program. In the most recent KARDIA-3 study, a single 300 mg dose of zilebesiran resulted in clinically meaningful, placebo-adjusted reductions in systolic blood pressure that were sustained for six months. The effect was particularly pronounced in patients also taking a diuretic, a common blood pressure medication.
“Zilebesiran has the potential to become a best-in-disease treatment for many patients with uncontrolled hypertension,” said Levi Garraway, Roche’s chief medical officer. “Its blood pressure-lowering effects and twice-yearly dosing could reduce the risk of serious health complications and death.”
Hypertension is a leading cause of cardiovascular disease worldwide, and up to 80% of patients fail to achieve adequate blood pressure control with existing daily medications. Poor adherence to daily pills is a major contributor to this problem. A long-acting therapy like zilebesiran, which targets angiotensinogen—a key protein in the body's blood pressure regulation system—could offer a transformative solution by ensuring continuous control.
The ZENITH study will compare zilebesiran to a placebo in patients who remain uncontrolled despite being on two or more standard hypertension therapies. The primary goal is to assess its impact on reducing cardiovascular death, heart attacks, strokes, and heart failure events.