Cambridge, Mass. — Alnylam Pharmaceuticals announced new clinical data presented at the European Society of Cardiology Congress 2026 highlighting the performance of its RNA interference, or RNAi, therapies across transthyretin amyloidosis with cardiomyopathy and uncontrolled hypertension.
The presentations included new analyses of AMVUTTRA (vutrisiran), as well as pooled Phase 3 data involving vutrisiran and patisiran. Alnylam also presented findings from a Phase 2 study of zilebesiran, its investigational RNAi therapy for hypertension.
“With the power of our RNAi therapeutics platform, we have the potential to make a transformational impact on cardiovascular care,” said Pushkal Garg, M.D., Chief Research and Development Officer at Alnylam. “The data presented at ESC demonstrate the consistency of clinical outcomes achieved by RNAi-powered TTR silencing, reinforcing our conviction in AMVUTTRA as a first-line treatment option for ATTR-CM. With zilebesiran, we have the potential to extend the precision and durability of RNAi to uncontrolled hypertension. Together, these programs reflect our ambition to change the course of cardiovascular disease for patients with high unmet need.”
A prespecified subgroup analysis of the Phase 3 HELIOS-B trial evaluated vutrisiran based on whether patients were receiving tafamidis at baseline. Among 654 randomized and treated patients, 259 were receiving tafamidis. The treatment effect of vutrisiran on the primary composite endpoint of all-cause mortality and recurrent cardiovascular events was consistent regardless of baseline tafamidis use.
Patients receiving vutrisiran also showed preservation of functional capacity compared with placebo, as measured by the Six-Minute Walk Test. Safety outcomes were generally similar between patients receiving vutrisiran with tafamidis and those receiving tafamidis alone, as well as between vutrisiran monotherapy and placebo.
Additional HELIOS-B analyses examined the broader effects of ATTR-CM and the potential impact of treatment beyond traditional cardiac measures. In one post hoc analysis, patients treated with vutrisiran experienced 25% less decline in intrinsic capacity from baseline and a 52% reduction in the risk of decline compared with placebo.
A separate safety analysis found that patients treated with vutrisiran had fewer adverse events overall than those receiving placebo. Gastrointestinal and nervous system disorders were reported at lower rates with vutrisiran, according to the analysis.
Alnylam also presented pooled data from 1,402 patients across four Phase 3 studies of vutrisiran and patisiran. The analysis found that treatment effects from RNAi-mediated TTR silencing were consistent between women and men across ATTR-CM and hereditary ATTR polyneuropathy.
“These data add to the deep and consistent evidence base supporting RNAi-mediated TTR silencing in ATTR-CM,” said Teresa Trenkwalder, M.D., Senior Physician at TUM University Hospital German Heart Center. “Across patient populations, treatment settings, and manifestations of disease, the analyses of vutrisiran demonstrate the clinical benefit that can be achieved by reducing TTR production at its source.”
Separately, Alnylam presented a subgroup analysis from the Phase 2 KARDIA-3 study of zilebesiran in patients with uncontrolled hypertension and high cardiovascular risk.
Among patients taking a background diuretic who had office systolic blood pressure of at least 140 mmHg at baseline, zilebesiran produced greater reductions in office and 24-hour ambulatory systolic blood pressure than were seen in the overall study population. The company said the findings support continued evaluation of zilebesiran in the ongoing Phase 3 ZENITH cardiovascular outcomes trial.
