Alnylam and Roche take zilebesiran into an 11,000-patient Phase 3 outcomes trial after KARDIA-3

Alnylam Pharmaceuticals/Zilebesiran

KARDIA-3, in high-risk patients already on two or more blood pressure drugs, showed a modest 5.0 mmHg office systolic drop with 300 mg at three months, larger (9.2 mmHg) in those on a diuretic with higher starting pressure. The partners chose 300 mg twice a year for ZENITH, a trial testing whether it reduces heart attacks, strokes, heart failure and cardiovascular deaths.

• 300 mg: -5.0 mmHg office systolic at month 3, -3.9 mmHg at month 6; 600 mg missed significance.
• Subgroup on a diuretic with systolic pressure of 140+: -9.2 mmHg at month 3.
• ZENITH: about 11,000 patients with uncontrolled hypertension and established or high cardiovascular risk.
• Primary endpoint: cardiovascular death, heart attack, stroke or heart failure events vs placebo.