Alnylam Presents New Data at ESC Congress 2026 Reinforcing RNAi-Powered TTR Silencing in ATTR-CM and Hypertension
核心洞察
A prespecified HELIOS-B subgroup analysis showed vutrisiran provided consistent benefit on all-cause mortality and recurrent cardiovascular events regardless of baseline tafamidis use in ATTR-CM patients.
Post hoc HELIOS-B analyses found vutrisiran preserved intrinsic capacity (25% less decline, 52% lower risk of decline) and reduced adverse event rates versus placebo.
A pooled analysis of 1,402 patients across four Phase 3 studies confirmed consistent vutrisiran and patisiran treatment effects across sexes.
Alnylam Pharmaceuticals (搜索), Inc. (Nasdaq: ALNY) presented new data at the European Society of Cardiology (ESC) Congress 2026 demonstrating the strength of RNAi-powered silencing for cardiovascular disease. The findings reinforce the clinical profile of AMVUTTRA® (vutrisiran) across transthyretin amyloidosis (ATTR) (搜索) patient populations, treatment settings, and manifestations of disease, while also expanding the potential application of RNAi to uncontrolled hypertension (搜索), the world's leading cause of cardiovascular disease.
"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 (搜索)."
HELIOS-B Subgroup Analysis Across Tafamidis Treatment Settings
A late-breaking oral presentation featured a prespecified subgroup analysis of the HELIOS-B Phase 3 clinical trial evaluating the treatment effect of vutrisiran according to baseline tafamidis use. The results were simultaneously published in the Journal of the American College of Cardiology.
Among 654 randomized and treated patients in HELIOS-B, 259 patients (40%) were receiving tafamidis at baseline. The treatment effect for vutrisiran on the primary composite endpoint of all-cause mortality and recurrent cardiovascular events through 33-36 months was consistent irrespective of baseline tafamidis use, suggesting clinical benefits across broad patient populations, including those receiving stabilizers.
All-cause mortality and additional cardiovascular outcomes showed a similar benefit among patients receiving tafamidis at baseline (the "combination population") and those who were not (the "monotherapy population"). Across both groups, treatment with vutrisiran preserved functional capacity versus placebo, as measured by the Six-Minute Walk Test. Improvement in health status by vutrisiran versus placebo, as measured by the Kansas City Cardiomyopathy Questionnaire-overall summary score, was observed in both the monotherapy and combination populations, with an attenuated effect seen among patients receiving tafamidis at baseline.
Safety outcomes were generally similar between combination vutrisiran and tafamidis versus tafamidis alone, and between vutrisiran monotherapy versus placebo. The study authors noted that HELIOS-B was not powered to establish the benefit of vutrisiran specifically in the population of patients receiving background tafamidis at baseline. These findings reinforce the impact of vutrisiran across contemporary ATTR-CM treatment settings and warrant further evaluation of TTR silencing and stabilization combination strategies.
Addressing the Multisystemic Burden of ATTR-CM
Additional analyses presented at ESC underscore the multisystemic burden of ATTR-CM and the importance of evaluating measures beyond traditional cardiac endpoints. Real-world evidence from the French National Health Data System showed that patients with ATTR-CM had a significantly higher burden of extra-cardiac manifestations across multiple organ systems compared with matched controls, and multiple manifestations were recorded years before ATTR-CM identification and tended to accumulate over time, suggesting a prolonged pre-diagnostic phase with evolving multisystem involvement.
A post hoc analysis of HELIOS-B evaluated the impact of treatment with vutrisiran on intrinsic capacity, a composite measure encompassing locomotion, cognition, vitality, psychological well-being and sensory function aligned with the World Health Organization Integrated Care for Older People framework. In the overall study population, compared with placebo, patients treated with vutrisiran demonstrated 25% less decline from baseline intrinsic capacity score and a 52% reduction in the risk of decline, suggesting that treatment with vutrisiran may help preserve functional reserve and support healthy aging in patients with ATTR-CM.
A separate post hoc safety analysis of HELIOS-B showed that patients treated with vutrisiran had fewer adverse events overall compared with placebo across the overall study population, monotherapy population and combination population. Among the most frequent system organ classes in the overall population, the lowest adverse event rate ratios were observed for gastrointestinal disorders and nervous system disorders, with 42% and 41% lower adverse event rates, respectively, with vutrisiran compared with placebo; eye disorders showed a 46% lower event rate with vutrisiran compared with placebo.
Consistent Treatment Effects Across Sexes
A pooled analysis of 1,402 patients (203 females, 1,199 males) across four Phase 3 studies of vutrisiran and patisiran further reinforces the clinical benefits of RNAi-mediated TTR silencing across sexes. Despite sex-specific baseline differences in disease presentation, treatment effects were consistent between females and males across both ATTR-CM and the polyneuropathy of hereditary ATTR (hATTR-PN), including clinical, biomarker, functional, health status and echocardiographic measures.
"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, 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."
Zilebesiran in Uncontrolled Hypertension
The KARDIA-3 Phase 2 study evaluated zilebesiran, an investigational RNAi therapeutic with the potential to provide continuous control of blood pressure (BP) with biannual dosing, in patients with uncontrolled hypertension (搜索) with high cardiovascular (CV) risk treated with two or more background antihypertensives. In patients who were receiving a background diuretic with an office systolic BP (SBP) ≥140 mmHg at baseline, zilebesiran achieved greater reductions in mean office and 24-hour ambulatory SBP than in the overall study population.
Furthermore, patients treated with zilebesiran experienced SBP reductions across the diurnal cycle, including at nighttime. Similar findings were observed in patients who had impaired nocturnal dipping at baseline. These findings are potentially important given the association between elevated nighttime BP and CV risk. The safety profile in this post hoc subgroup was consistent with the broader zilebesiran Phase 2 program. These findings further support the evaluation of zilebesiran in the ongoing global Phase 3 CV outcomes trial, ZENITH.
About Vutrisiran and ATTR
AMVUTTRA® (vutrisiran) demonstrates strength in RNAi-powered transthyretin (TTR) (搜索) silencing, delivering rapid knockdown of TTR at the source of disease to address the underlying cause of transthyretin amyloidosis (ATTR) (搜索). In the HELIOS-B Phase 3 study, AMVUTTRA reduced the risk of all-cause mortality and recurrent CV events compared to placebo in the overall and monotherapy populations by 28.2% and 32.8%, respectively, through 36 months. It is the only TTR silencer approved for both hATTR-PN and ATTR-CM in countries globally, and is administered once quarterly via subcutaneous injection.
Transthyretin amyloidosis (ATTR) (搜索) is an underdiagnosed, rapidly progressive, debilitating, and fatal disease caused by pathogenic transthyretin (TTR) (搜索) proteins, which accumulate as amyloid deposits in various parts of the body, including the nerves, heart, and gastrointestinal tract. It is estimated that more than 500,000 people worldwide live with ATTR, with approximately 80% remaining undiagnosed.
Zilebesiran is an investigational, subcutaneously administered RNAi therapeutic targeting angiotensinogen (AGT) (搜索), the most upstream precursor in the renin-angiotensin-aldosterone system (RAAS). It is being co-developed and co-commercialized by Alnylam and Roche, and its safety and efficacy have not been established or evaluated by the FDA, EMA, or any other health authority.