Key Highlights
- Roche and Alnylam advance zilebesiran, a first-in-class RNAi therapy, into global Phase III ZENITH outcomes trial.
- KARDIA-3 Phase II data shows meaningful blood pressure reductions with twice-yearly dosing.
- ZENITH to enroll 11,000 patients across 30 countries, targeting uncontrolled hypertension and high cardiovascular risk.
Phase II Data Paves the Way
The KARDIA clinical program—spanning three Phase II trials—has provided the foundation for moving zilebesiran into Phase III. In KARDIA-3, a single 300 mg injection every six months demonstrated clinically meaningful blood pressure reduction, with stronger benefits observed in patients on diuretics and with higher baseline systolic pressure. While statistical thresholds were not fully met, the trial succeeded in identifying patient populations most likely to benefit.
ZENITH: A Landmark Global Study
The ZENITH Phase III cardiovascular outcomes trial will recruit approximately 11,000 patients across 30+ countries. It will evaluate zilebesiran’s impact on reducing major adverse cardiovascular events—including CV death, heart attack, stroke, and heart failure hospitalizations—versus placebo. The trial is designed for patients with uncontrolled hypertension on multiple therapies, signaling the ambition to set a new standard of care.
Why Zilebesiran Matters
Hypertension remains the leading modifiable risk factor for cardiovascular disease, affecting over 1.2 billion people worldwide. Despite the availability of daily oral antihypertensives, up to 80% of patients fail to achieve adequate control. Zilebesiran’s twice-yearly dosing via subcutaneous injection could overcome adherence challenges, providing continuous blood pressure control and lowering long-term cardiovascular risks.
Industry Impact and Innovation
RNA interference (RNAi), the therapeutic platform behind zilebesiran, has been hailed as a once-in-a-decade breakthrough in biology. By targeting angiotensinogen upstream in the RAAS pathway, zilebesiran aims to provide durable reductions in blood pressure while integrating seamlessly with existing therapies. If successful, the therapy could mark a paradigm shift in hypertension management, reducing disease burden on patients and healthcare systems alike.
About Roche
Roche, founded in 1896 in Basel, Switzerland, is the world’s largest biotechnology company and a leader in in-vitro diagnostics. With over 125 years of scientific innovation, Roche is advancing personalized healthcare by combining pharmaceuticals, diagnostics, and real-world data insights. The company is committed to sustainable healthcare transformation and achieving net-zero emissions by 2045.
About Alnylam
Alnylam Pharmaceuticals, headquartered in Cambridge, Massachusetts, is a pioneering biopharmaceutical company focused on RNA interference (RNAi) therapeutics. With multiple FDA-approved products and a growing late-stage pipeline, Alnylam is redefining the treatment landscape for genetic and cardiometabolic diseases. Its collaboration with Roche on zilebesiran underscores a shared vision to tackle hypertension and cardiovascular risk at a global scale.
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