Alnylam Pharmaceuticals presented new data from its landmark HELIOS-B Phase 3 clinical trial at the American College of Cardiology's Annual Scientific Session (ACC.25) in Chicago, further validating the efficacy of vutrisiran (AMVUTTRA) in treating transthyretin amyloidosis with cardiomyopathy (ATTR-CM).
The presentations follow the recent U.S. Food and Drug Administration approval of AMVUTTRA for the treatment of cardiomyopathy in adults with wild-type or hereditary transthyretin-mediated amyloidosis. This approval, announced on March 20, 2025, established AMVUTTRA as the first RNAi therapeutic approved to reduce cardiovascular mortality, cardiovascular hospitalizations, and urgent heart failure visits in ATTR-CM patients.
Improved Cardiac Structure and Function
New echocardiographic data from HELIOS-B, described as the largest systematic echocardiographic study in a pivotal trial, demonstrated that vutrisiran treatment significantly improved cardiac function compared to placebo.
Patients receiving vutrisiran showed significant improvements in diastolic function and attenuated declines in both left ventricular (LV) and right ventricular (RV) systolic function at 18 months. The study revealed that worsening LV and RV systolic function over 18 months was significantly associated with an increased risk of subsequent all-cause death, highlighting the clinical importance of these parameters.
"The HELIOS-B study continues to deliver a robust data package showcasing the unique, differentiated value of vutrisiran as a first-line treatment option that can enable patients with ATTR-CM to live longer, better, and healthier lives," said Pushkal Garg, M.D., Chief Medical Officer of Alnylam. "Data showing beneficial effects on cardiac systolic and diastolic function are novel and indicate the direct impact of vutrisiran in cardiac structure and function of patients living with ATTR-CM."
Early Intervention Shows Greatest Benefit
An exploratory subgroup analysis presented at ACC.25 demonstrated that vutrisiran reduced all-cause mortality and recurrent cardiovascular events across a range of baseline heart failure severities in ATTR-CM patients. Notably, the greatest benefit was observed in patients with earlier, less severe disease, underscoring the importance of early diagnosis and intervention.
Similar effects were observed in the monotherapy population and across additional endpoints, including functional capacity and cardiac biomarkers, reinforcing vutrisiran's efficacy regardless of disease stage. These results were recently published in the Journal of the American College of Cardiology (JACC).
Quality of Life Improvements
A separate analysis confirmed that vutrisiran significantly maintained or improved functional capacity and patient-reported health status and quality of life compared to placebo over 30 months. Greater proportions of patients treated with vutrisiran preserved or improved 6-minute walk test distance and Kansas City Cardiomyopathy Questionnaire scores at clinically meaningful thresholds.
"The HELIOS-B clinical trial found that vutrisiran allowed patients to live longer, experience fewer hospitalizations, and improve how they function and feel," said Ronald Witteles, M.D., HELIOS-B Investigator, Professor of Medicine at Stanford University School of Medicine and Co-Director of the Stanford Amyloid Center. "The trial enrolled patients who mirror the real-world population with this disease, and I am very encouraged by vutrisiran's ability to demonstrate meaningful clinical benefits across both cardiovascular outcomes and multiple measures of disease progression."
Novel Mechanism of Action
AMVUTTRA is an RNAi therapeutic that works by delivering rapid knockdown of transthyretin (TTR), addressing the disease at its source. Administered quarterly via subcutaneous injection, AMVUTTRA substantially decreases deposition of TTR fibrils, which form amyloid and cause irreversible cardiovascular damage in patients with ATTR-CM.
ATTR amyloidosis is an underdiagnosed, rapidly progressive, debilitating, and fatal disease caused by misfolded TTR proteins that accumulate as amyloid deposits in various parts of the body, including the nerves, heart, and gastrointestinal tract. It affects approximately 50,000 people worldwide in its hereditary form (hATTR) and an estimated 200,000-300,000 people worldwide in its wild-type form (wtATTR).
Comprehensive Patient Support
Alnylam offers multiple support services for patients prescribed AMVUTTRA through Alnylam Assist®, the only in-house patient support program in ATTR-CM. The program provides one-on-one support for patients and healthcare teams, including insurance coverage assistance, financial assistance, and disease and treatment education.
The company reports that AMVUTTRA for hATTR-PN is covered by insurers for approximately 99% of patients, with the majority paying $0 out-of-pocket. Similar broad coverage and out-of-pocket costs are expected for ATTR-CM patients.
Marketing authorization applications based on HELIOS-B data are currently under review by several global health agencies, including the European Medicines Agency, the Brazilian Health Regulatory Agency, and the Japanese Pharmaceuticals and Medical Devices Agency. Alnylam remains on track to proceed with additional global regulatory submissions for vutrisiran in 2025.
