Zilebesiran - (KARDIA-3)

ESC Congress 2026: Alnylam Pharmaceuticals (NASDAQ: ALNY) presented new analyses on vutrisiran (AMVUTTRA) and zilebesiran.

For vutrisiran in ATTR-CM, a prespecified subgroup analysis from the Phase 3 HELIOS-B trial (n=654; 40% on tafamidis at baseline) showed the primary composite endpoint of all-cause mortality plus recurrent cardiovascular events through 33-36 months was consistently improved versus placebo regardless of baseline tafamidis use. Benefits on all-cause mortality, other cardiovascular outcomes, and 6-minute walk test were similar in monotherapy and combination groups; Kansas City Cardiomyopathy Questionnaire benefit was seen in both groups but attenuated with baseline tafamidis. Safety was generally similar; the study was not powered to prove benefit specifically in patients on background tafamidis.

Additional HELIOS-B post hoc analyses showed 25% less decline in intrinsic capacity and a 52% lower risk of decline versus placebo, plus fewer adverse events overall, including lower gastrointestinal, nervous system, and eye disorder event rates. A pooled analysis across four positive Phase 3 studies of vutrisiran and patisiran (1,402 patients) showed consistent treatment effects across sexes in ATTR-CM and hATTR-PN.

For zilebesiran, a post hoc subgroup analysis from the Phase 2 KARDIA-3 study in uncontrolled hypertension found greater office and 24-hour ambulatory systolic BP reductions in patients on a background diuretic with baseline office SBP ≥140 mmHg, including nighttime BP reductions; Phase 3 ZENITH is ongoing. Alnylam’s RNAi Roundtable on zilebesiran is scheduled for September 17, 2026.