Madrid, Spain – New analyses from the pivotal HELIOS-B Phase 3 study of vutrisiran (AMVUTTRA®) have revealed compelling long-term cardiovascular benefits for patients suffering from transthyretin-mediated amyloidosis with cardiomyopathy (ATTR-CM). Presented at the highly popular European Society of Cardiology (ESC) Congress 2025, these findings underscore vutrisiran’s potential to significantly alter the course of this progressive and life-threatening disease. The data, encompassing up to 48 months of treatment including a 12-month open-label extension, reinforce the drug’s established safety profile and its role in improving patient outcomes.
ATTR-CM: A Growing Challenge in Cardiology
Transthyretin-mediated amyloidosis with cardiomyopathy (ATTR-CM) is a debilitating condition characterized by the misfolding and deposition of transthyretin (TTR) protein, leading to progressive stiffening of the heart muscle and eventual heart failure. This disease is increasingly recognized as an underdiagnosed contributor to heart failure, particularly in elderly patients. Patients may present with polyneuropathy, cardiomyopathy, or both manifestations of disease. Historically, ATTR-CM has had limited therapeutic options, but the growing understanding and development of targeted therapies, such as RNA interference (RNAi) agents like vutrisiran, represent significant advancements in addressing this unmet medical need.
HELIOS-B Study: Unveiling Long-Term Efficacy and Mechanism
The HELIOS-B study, a landmark Phase 3 trial, was designed to evaluate the efficacy and safety of vutrisiran, an RNAi therapeutic developed by Alnylam Pharmaceuticals. Vutrisiran works by targeting the liver to reduce the production of TTR protein, addressing the root cause of ATTR-CM. Administered quarterly via subcutaneous injection, it delivers rapid knockdown of the disease-causing TTR protein. The trial enrolled 654 patients with ATTR-CM, with 466 proceeding into the open-label extension (OLE) period. The recent presentations at the ESC Congress 2025 focused on updated data, extending follow-up to up to 48 months, providing crucial insights into the drug’s sustained impact.
Sustained Cardiovascular Protection and Mortality Reduction
The most striking findings from the HELIOS-B study presented at ESC Congress 2025 highlighted vutrisiran’s ability to deliver sustained cardiovascular benefits. Over a period of up to 48 months, including the 12-month OLE period, vutrisiran demonstrated a significant reduction in the composite endpoint of all-cause mortality or first cardiovascular event, showing a 37% risk reduction in the overall population and an even more substantial 42% reduction in the monotherapy group, both with high statistical significance (p<0.001). Furthermore, vutrisiran also reduced the risk of all-cause mortality alone by 37% in the overall population (p<0.01) and 39% in the monotherapy group (p<0.01). These results underscore the potential of vutrisiran to improve survival and reduce cardiovascular morbidity.
Improving Quality of Life and Functional Capacity
Beyond mortality and major cardiovascular events, the new analyses from HELIOS-B also confirmed vutrisiran’s positive impact on patient-reported outcomes and disease progression markers. Treatment with vutrisiran consistently maintained or improved quality of life, as measured by the Kansas City Cardiomyopathy Questionnaire Overall Summary (KCCQ-OS), showing a mean improvement of 8.95 points in the overall population and 11.40 points in the monotherapy group. This indicates a tangible enhancement in daily living and well-being. Additionally, the drug preserved functional capacity, with data showing less decline in the 6-minute walk test compared to placebo, and reduced cardiac biomarkers such as NT-proBNP and Troponin I, further signaling a slowdown in disease progression. A post hoc analysis also highlighted a significant practical benefit, showing vutrisiran was associated with a reduction of 32.2 days lost to death and/or hospitalization over three years compared to placebo.
Consistent Safety Profile Reinforces Long-Term Viability
Crucially, the safety and tolerability profile of vutrisiran observed during the 12-month open-label extension period remained consistent with data from the double-blind phase. No new safety concerns were identified, and the rates of adverse events, including serious adverse events and cardiac events, did not increase with longer treatment duration. Patients receiving vutrisiran did experience reduced serum vitamin A levels, necessitating supplementation. Alnylam Pharmaceuticals reiterated that the overall safety and tolerability of vutrisiran in the extended treatment period were reassuring, making it a viable long-term option.
Vutrisiran’s Evolving Role in ATTR-CM Management
These comprehensive long-term data from the HELIOS-B study, presented at the ESC Congress 2025, significantly bolster the evidence supporting vutrisiran as a potentially transformative, first-line treatment for ATTR-CM. The findings emphasize the critical importance of early diagnosis and initiation of therapy to maximize benefits. With global approvals already secured in key regions, including the U.S., European Union, Japan, and the UK, for both ATTR-CM and hATTR-PN, vutrisiran offers a vital option for patients. The accumulating patient-years of experience worldwide further validate its clinical utility.
Conclusion
The latest insights from the HELIOS-B study presented at the ESC Congress 2025 mark a significant milestone in the management of ATTR-CM. Vutrisiran has demonstrated sustained and substantial cardiovascular benefits, improving survival, reducing cardiac events, and enhancing quality of life, all while maintaining a favorable safety profile. As the medical community continues to deepen its understanding of ATTR-CM, these findings solidify vutrisiran’s role as a cornerstone therapy, offering renewed hope for patients facing this challenging diagnosis. This important medical news highlights the ongoing progress in bringing innovative treatments to those in need.
