Alnylam reports five-year HELIOS-B findings showing lower mortality and cardiovascular event risks, better quality of life and preserved exercise capacity with vutrisiran in ATTR-CM.
Written By: Sravani Pamanji, PharmD
Reviewed By: Pharmacally Editorial Team
Alnylam Pharmaceuticals announced five-year findings from its Phase 3 HELIOS-B study on November 9, 2026, demonstrating sustained cardiovascular benefits of AMVUTTRA® (vutrisiran) in patients with transthyretin amyloidosis with cardiomyopathy (ATTR-CM). Presented at the American Heart Association (AHA) Scientific Sessions 2026, the findings showed more favourable long-term outcomes among patients who received continuous vutrisiran treatment than those who initiated treatment approximately three years later.
The analyses demonstrated lower risks of all-cause mortality and recurrent cardiovascular (CV) events, better-preserved quality of life and greater stability in cardiac biomarkers through 60 months. A separate post hoc analysis also provided evidence of preserved exercise capacity and favourable changes in cardiopulmonary function.
Understanding the HELIOS-B Study
HELIOS-B (NCT04153149) is a Phase 3, randomized, double-blind, placebo-controlled, multicentre study evaluating the efficacy and safety of vutrisiran in patients with ATTR-CM. The trial enrolled 655 participants who initially received either vutrisiran 25 mg or placebo through subcutaneous administration once every three months during the 36-month double-blind period.
This was followed by an open-label extension (OLE) of up to 24 months, during which participants initially assigned to placebo could transition to vutrisiran. The five-year analyses included 654 participants in the overall population and 395 in the monotherapy population, which comprised patients not receiving tafamidis at baseline.
These analyses enabled comparisons between patients receiving continuous vutrisiran treatment and those who initiated treatment during the OLE period, approximately three years later.
Sustained Cardiovascular Benefits Over Five Years
Continuous vutrisiran treatment demonstrated favourable outcomes across both the monotherapy and overall populations. Compared with delayed treatment initiation, continuous treatment was associated with a 48% lower risk of all-cause mortality and recurrent CV events in the monotherapy population and a 41% lower risk in the overall population.
The risk of recurrent CV events was also reduced by 50% and 41%, respectively. Similarly, the risk of all-cause mortality or a first CV event was 48% lower in the monotherapy population and 39% lower in the overall population.
Patients receiving continuous treatment also maintained better quality of life, measured using the Kansas City Cardiomyopathy Questionnaire Overall Summary (KCCQ-OS) score. The least-squares mean differences were 11.66 points in the monotherapy population and 9.68 points in the overall population, with both comparisons reporting p<0.0001.
Greater stability in cardiac biomarkers, including N-terminal pro-B-type natriuretic peptide (NT-proBNP) and troponin I, was also observed.
Among patients receiving tafamidis at baseline, continuous treatment with vutrisiran alongside tafamidis was associated with a 23% reduction in recurrent CV events compared with delayed vutrisiran initiation (relative risk: 0.766; 95% CI: 0.597–0.984; p=0.0366).
The safety profile through 60 months remained consistent with the previously established profile, with no new safety signals identified. The reported p-values for the long-term efficacy endpoints were nominal and were not adjusted for multiplicity.
Exercise Capacity and Cardiopulmonary Function
A separate post hoc, single-centre analysis of 48 HELIOS-B participants evaluated the effects of vutrisiran on exercise capacity and cardiopulmonary function. Participants underwent cardiopulmonary exercise testing (CPET) alongside stress echocardiography at the National Amyloidosis Centre in London.
Over two years, vutrisiran demonstrated better preservation of exercise capacity compared with placebo, measured by peak oxygen uptake (VO₂). The least-squares mean difference was 1.57 mL/kg/min (95% CI: 0.14–3.00; p=0.031).
The analysis also showed preservation of chronotropic response and improved ventilatory efficiency. Stress echocardiography demonstrated favourable changes in measures of right ventricular systolic reserve and left ventricular diastolic reserve. No participants received other ATTR-CM disease-modifying therapies during the study period.
These findings provide additional physiological evidence of the potential effects of TTR silencing on maintaining the cardiovascular system’s response to physical activity. However, the small sample size and post hoc design warrant cautious interpretation.
How Vutrisiran Works
AMVUTTRA® (vutrisiran) is a small interfering RNA (siRNA)-based RNA interference (RNAi) therapeutic designed to reduce transthyretin (TTR) production at its source.
The treatment targets TTR messenger RNA (mRNA) in the liver, reducing the production of the transthyretin protein. In patients with ATTR-CM, abnormal transthyretin proteins accumulate as amyloid deposits in the heart, contributing to progressive cardiac dysfunction. By suppressing hepatic TTR production, vutrisiran addresses an underlying mechanism of the disease.
The treatment is administered as a subcutaneous injection once every three months. Its established safety considerations include reduced serum vitamin A levels, for which supplementation at the recommended daily allowance is advised.
Clinical Interpretation
The five-year HELIOS-B findings strengthen the evidence supporting sustained TTR silencing in patients with ATTR-CM. The lower risks of mortality and recurrent cardiovascular events, together with better-preserved quality of life and greater cardiac biomarker stability, highlight the potential importance of initiating treatment earlier.
The findings also provide a clinically relevant distinction between continuous and delayed treatment initiation. Patients who began vutrisiran earlier maintained more favourable outcomes than those who transitioned from placebo approximately three years later, supporting the potential value of earlier intervention in this progressive disease.
The exercise-related findings add a functional dimension to the evidence, suggesting that vutrisiran may help preserve exercise capacity and aspects of cardiopulmonary function. Nevertheless, these results come from a small post hoc analysis and require further evaluation.
Importantly, the five-year comparison reflects continuous versus delayed treatment rather than a five-year placebo-controlled assessment. The results therefore support the potential benefits of early and sustained treatment but should be interpreted within the design and statistical limitations of the analyses.
Reference
Alnylam Announces Five-Year HELIOS-B Data Demonstrating Sustained Benefit of AMVUTTRA® (vutrisiran) in ATTR-CM. November 9, 2026.
HELIOS-B: A Study to Evaluate Vutrisiran in Patients with Transthyretin Amyloidosis with Cardiomyopathy. ClinicalTrials.gov ID NCT04153149
About the Writer
Sravani Pamanji is a PharmD (LinkedIn) professional with experience in scientific writing, medical literature review, drug profile preparation, and clinical case documentation. She has contributed to scientific publication and presented at the 74th Indian Pharmaceutical Congress. Her training includes ICH GCP E6(R3), scientific research, and medication safety. She is passionate about evidence-based medical communication and accurate dissemination of clinical and pharmaceutical information.