Alnylam Pharmaceuticals presents results from KARDIA-2 Phase 2 study

Alnylam Pharmaceuticals announced positive results from the KARDIA-2 Phase 2 study evaluating the efficacy and safety of a single subcutaneous dose of zilebesiran when added to one of three standard of care antihypertensives including a thiazide-like diuretic, calcium channel blocker or angiotensin receptor blocker. Zilebesiran is an investigational RNAi therapeutic targeting liver-expressed angiotensinogen in development for the treatment of hypertension with the potential for biannual dosing. The results were presented as a late-breaking clinical trial at the 2024 American College of Cardiology Annual Scientific Session. The company previously announced topline results from the KARDIA-2 study in March 2024. The KARDIA-2 study achieved its primary endpoint demonstrating clinically and statistically significant additive, placebo-adjusted reductions of up to 12.1 mmHg in 24-hour mean systolic blood pressure measured by ambulatory blood pressure monitoring when zilebesiran was added to a thiazide-like diuretic, calcium channel blocker or angiotensin receptor blocker, measured independently at Month 3. The study achieved the key secondary endpoint evaluated at Month 3, demonstrating clinically significant additive reductions in office SBP across all three independent cohorts. At Month 6, zilebesiran demonstrated clinically significant and sustained placebo-adjusted, time-adjusted reductions in office SBP when added to indapamide, amlodipine and olmesartan, despite the addition of rescue antihypertensives at Month 3. In addition, zilebesiran resulted in clinically significant placebo-adjusted, time-adjusted reductions in 24-hour mean SBP, assessed by ABPM, when added to indapamide and amlodipine, sustained to Month 6. A non-statistically significant result was observed when zilebesiran was added to the maximum dose of olmesartan when evaluated by time-adjusted change from baseline in 24-hour mean SBP, assessed by ABPM at Month 6. Most laboratory abnormalities of interest were mild, occurred in the first three months of treatment and resolved upon repeat measure within one to two weeks without intervention. There were no deaths reported, and no AEs led to study discontinuation during the six-month double-blind period.