Cambridge, Mass. – August 30, 2026
Alnylam Pharmaceuticals announced new clinical data at the European Society of Cardiology (ESC) Congress 2026, reinforcing the company’s position in RNA interference (RNAi)-based cardiovascular therapeutics. The company highlighted new analyses of AMVUTTRA® (vutrisiran) across transthyretin amyloidosis with cardiomyopathy (ATTR-CM) populations and treatment settings, together with new data supporting the potential of investigational zilebesiran in uncontrolled hypertension. The ESC presentations build on Alnylam’s broader clinical development strategy of using RNAi to achieve sustained suppression of disease-driving proteins and expand treatment options for cardiovascular diseases with substantial unmet need. The company particularly emphasized findings from the HELIOS-B Phase 3 study, which showed consistent clinical benefit with vutrisiran regardless of whether patients were receiving background tafamidis at study entry. Alnylam said the findings further support the potential role of TTR silencing across contemporary ATTR-CM treatment approaches.
HELIOS-B Data Support Consistent Vutrisiran Benefit
The HELIOS-B prespecified subgroup analysis evaluated the effect of vutrisiran according to baseline tafamidis use among 654 randomized and treated patients, including 259 patients who were receiving tafamidis at baseline. According to Alnylam, the treatment effect on the composite endpoint of all-cause mortality and recurrent cardiovascular events through approximately three years was consistent in patients receiving tafamidis and those treated without background tafamidis. The analysis also showed preservation of functional capacity measured by the Six-Minute Walk Test, while health-status outcomes measured using the Kansas City Cardiomyopathy Questionnaire generally favored vutrisiran in both treatment populations. Alnylam emphasized that HELIOS-B was not specifically powered to establish efficacy in the tafamidis subgroup, making these findings supportive rather than definitive for combination treatment. The company also presented additional analyses examining the broader systemic burden of ATTR-CM, highlighting potential effects of vutrisiran beyond traditional cardiac endpoints.
Alnylam Expands Evidence Around Multisystem ATTR-CM
Additional HELIOS-B analyses presented at ESC 2026 focused on the multisystem nature of ATTR-CM and the potential impact of TTR silencing on patients’ broader functional health. A post hoc analysis found that patients receiving vutrisiran experienced 25% less decline in intrinsic capacity compared with placebo and a 52% reduction in the risk of intrinsic-capacity decline. Intrinsic capacity incorporates domains including locomotion, cognition, vitality, psychological well-being and sensory function, providing a broader view of patient function. Alnylam also highlighted real-world evidence indicating that extra-cardiac manifestations of ATTR-CM may occur years before formal diagnosis and can accumulate over time. Separately, a pooled analysis involving 1,402 patients across four Phase 3 studies of vutrisiran and patisiran showed generally consistent treatment effects across females and males. Together, these analyses add to Alnylam’s effort to demonstrate the relevance of RNAi-powered TTR silencing across different patient characteristics and manifestations of ATTR.
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Zilebesiran Strengthens Alnylam’s Cardiovascular Pipeline
Beyond ATTR-CM, Alnylam presented new KARDIA-3 Phase 2 subgroup data for zilebesiran, an investigational RNAi therapeutic targeting angiotensinogen (AGT) for sustained blood-pressure control. In patients with uncontrolled hypertension who were receiving background diuretic therapy and had office systolic blood pressure of at least 140 mmHg, zilebesiran produced greater reductions in office and 24-hour ambulatory systolic blood pressure than observed in the overall study population. Blood-pressure reductions were also observed across the day-night cycle, including nighttime measurements, with similar findings in patients who had impaired nocturnal blood-pressure dipping. Alnylam said these findings support continued evaluation of zilebesiran in the ongoing Phase 3 ZENITH cardiovascular outcomes trial. Overall, the ESC 2026 data strengthen Alnylam’s strategy of applying RNAi technology to major cardiovascular diseases, with vutrisiran providing established clinical evidence in ATTR-CM and zilebesiran representing a potential future approach to durable hypertension management. However, zilebesiran remains investigational, and its efficacy and safety have not been established by regulatory authorities.
Source:Alnylam Pharmaceuticals, press relese
