Cambridge, Massachusetts, United States, November 9, 2026
Alnylam Pharmaceuticals, Inc. has announced encouraging five-year clinical findings from its HELIOS-B Phase 3 study, demonstrating sustained cardiovascular benefits of AMVUTTRA® (vutrisiran) in adults with transthyretin amyloidosis with cardiomyopathy (ATTR-CM). The long-term results show that patients who started vutrisiran earlier and continued treatment experienced more favorable outcomes across mortality, recurrent cardiovascular events, quality of life and cardiac biomarkers than patients who initially received placebo and began treatment later. The findings were presented at the American Heart Association (AHA) Scientific Sessions 2026 in Chicago, Illinois. The analyses include data from the study’s two-year open-label extension (OLE), extending observations to 60 months. In the overall study population, continuous vutrisiran treatment was associated with a 41% lower risk of the composite of all-cause mortality and recurrent cardiovascular events compared with delayed treatment initiation. In the monotherapy population, the relative risk reduction was 48%. The results strengthen the clinical evidence for RNA interference (RNAi)-based treatment and highlight the potential importance of early intervention in this progressive cardiac disease.
HELIOS-B Shows Sustained Cardiovascular Benefits Over Five Years
The HELIOS-B Phase 3 clinical trial evaluated vutrisiran in adults with ATTR-CM, a condition caused by the accumulation of misfolded transthyretin proteins in the heart. During the original double-blind study period, participants were randomized to receive vutrisiran or placebo. Eligible participants subsequently entered the open-label extension, during which those initially assigned to placebo could transition to vutrisiran. This design enabled researchers to compare outcomes between patients who received continuous treatment and those who started treatment later. At the 60-month assessment, continuous vutrisiran treatment was associated with a 48% relative reduction in the risk of all-cause mortality and recurrent cardiovascular events in the monotherapy population, which included 395 participants. In the overall population of 654 participants, the corresponding reduction was 41%. The risk of recurrent cardiovascular events alone was reduced by 50% in the monotherapy population and 41% in the overall population. Patients who began treatment earlier also maintained better quality of life, measured using the Kansas City Cardiomyopathy Questionnaire Overall Summary (KCCQ-OS), and showed greater stability in cardiac biomarkers, including NT-proBNP and troponin I. These findings indicate sustained differences between earlier and delayed treatment initiation, although the comparisons should be interpreted in the context of the open-label extension design and the statistical analyses reported.
Exercise Capacity and Cardiac Function Findings
A separate post hoc analysis of HELIOS-B examined how vutrisiran affected patients’ cardiopulmonary responses during physical activity. The analysis included 48 participants who underwent cardiopulmonary exercise testing (CPET) alongside stress echocardiography at the National Amyloidosis Centre in London. Researchers evaluated exercise capacity, heart-rate response, ventilatory efficiency and cardiac function during exercise. Compared with placebo, vutrisiran preserved exercise capacity, measured by peak oxygen uptake (VO₂), with a least-squares mean difference of 1.57 mL/kg/min over two years. The analysis also indicated preservation of the chronotropic response, which describes the heart’s ability to increase its rate during physical activity, and improvements in ventilatory efficiency. Stress echocardiography demonstrated favorable changes in measures of right ventricular systolic reserve and left ventricular diastolic reserve. These findings are relevant because exercise intolerance is a common feature of ATTR-CM and can progressively restrict patients’ daily activities as the disease advances. However, this was a small, single-center, post hoc analysis, and its findings should be considered exploratory rather than definitive evidence of improved long-term exercise outcomes.
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RNAi Therapy Targets the Underlying Cause of ATTR
AMVUTTRA (vutrisiran) is an RNAi therapeutic designed to reduce the production of transthyretin (TTR) protein in the liver. It uses small interfering RNA (siRNA) to silence messenger RNA responsible for producing TTR, thereby reducing the supply of the protein that can form harmful amyloid deposits in the heart and other tissues. ATTR occurs in two main forms: hereditary ATTR, associated with genetic variants in the TTR gene, and wild-type ATTR, which develops without an inherited TTR mutation. Both forms can cause cardiomyopathy, while hereditary disease may also involve progressive nerve damage. AMVUTTRA is administered through a subcutaneous injection once every three months. It is approved in the United States for adults with wild-type or hereditary ATTR-CM to reduce cardiovascular mortality, cardiovascular hospitalizations and urgent heart failure visits. It is also approved for adults with hereditary ATTR polyneuropathy. Alnylam reported that the safety profile remained consistent through 60 months, with no new safety signals identified. Treatment can reduce serum vitamin A levels, so recommended daily allowance vitamin A supplementation is advised according to prescribing information. The five-year HELIOS-B findings add important long-term evidence supporting TTR silencing and the role of earlier treatment in managing ATTR-CM.
Source: Alnylam Pharmaceuticals press release
