Zilebesiran Demonstrates Effective Blood Pressure Reduction in Phase II Trial

Alnylam Therapeutics, in collaboration with Roche, has reported that its experimental hypertension treatment, zilebesiran, has successfully achieved its primary goal in a Phase II clinical trial. Zilebesiran is an RNA interference (RNAi) therapeutic targeting liver-expressed angiotensinogen (AGT), and it has demonstrated a significant decrease in average 24-hour systolic blood pressure by the third month of treatment.

The KARDIA-2 trial incorporated zilebesiran as an adjunct to three conventional hypertension medications: indapamide, amlodipine, and olmesartan. Although specific data were not released, Alnylam highlighted that the drug exhibited promising safety and tolerability when combined with these treatments. The company is optimistic about the Phase II study outcomes and intends to unveil the comprehensive results at the American College of Cardiology's Annual Scientific Session in April 2024.

Simon Fox, Alnylam's vice president and lead for the zilebesiran program, expressed enthusiasm about the drug's potential, noting that a single dose of zilebesiran resulted in clinically meaningful reductions in systolic blood pressure for patients whose hypertension was not well-managed by standard antihypertensive drugs. The KARDIA-2 trial's results, which showed sustained blood pressure reduction on top of standard treatments with a favorable safety profile, have bolstered Alnylam's confidence in zilebesiran's unique therapeutic profile.

Initiated in 2021, the global study is expected to conclude in 2025 and has enrolled 672 hypertension patients. Additionally, Roche and Alnylam have commenced another Phase II study to explore zilebesiran as an add-on therapy for adults at high cardiovascular risk with uncontrolled hypertension despite the use of multiple antihypertensive medications. The primary goal of this study will be to measure the change in mean seated office systolic blood pressure at month three.

Further objectives of the ongoing research include assessing changes in 24-hour mean systolic blood pressure through ambulatory blood pressure monitoring at the third month and changes in seated office systolic blood pressure at the sixth month. Alnylam is also planning adjustments to a Phase III trial for its RNAi therapy, Amvuttra (vutrisiran), for patients with ATTR amyloidosis and cardiomyopathy, modifying the primary and secondary endpoints of the study.