New Findings from Landmark HELIOS-B Phase 3 Study Show Vutrisiran's Long-Term Cardiovascular Benefits in ATTR-CM at ESC Congress 2025

Vutrisiran Clinical Study Results

• Long-term Efficacy: Vutrisiran has demonstrated sustained clinical benefits across mortality, cardiovascular events, quality of life, and cardiac biomarkers over a period of up to 48 months, including 12 months from the ongoing open-label extension (OLE) of the HELIOS-B Phase 3 study.
• Risk Reduction: The treatment reduced the risk of the composite endpoint of all-cause mortality or first cardiovascular event by 37% in the overall population and 42% in the monotherapy group, with statistical significance (p<0.001).

Study Details and Findings

• Patient Population: The HELIOS-B trial included 654 patients, with 466 entering the OLE period. Vital status was confirmed for over 99% of patients by the data cutoff on April 9, 2025.
• Quality of Life Improvements: Vutrisiran treatment resulted in a significant improvement in quality of life, as measured by the Kansas City Cardiomyopathy Questionnaire Overall Summary (KCCQ-OS), with a mean difference of 8.95 points in the overall population (p<0.0001) and 11.40 points in the monotherapy group (p<0.0001).

Safety and Tolerability

• Safety Profile: The long-term safety and tolerability of vutrisiran were consistent with previous reports, showing no increase in adverse events (AEs) or serious adverse events (SAEs) with extended treatment duration.
• Vitamin A Levels: Patients receiving vutrisiran experienced reduced serum vitamin A levels, necessitating supplementation of 2500 to 3000 IU per day.

Implications for Treatment

• First-Line Treatment Potential: The results support the potential of vutrisiran as a first-line therapy for patients with ATTR-CM, emphasizing the importance of early treatment initiation.
• Days Lost to Death and Hospitalization: A post hoc analysis indicated that vutrisiran was associated with a reduction of 32.2 days lost to death and/or hospitalization over three years compared to placebo.

Regulatory Approvals and Global Experience

• Global Approvals: Vutrisiran has received approvals in multiple regions, including the US, EU, Japan, and the UK, for treating both the cardiomyopathy and polyneuropathy manifestations of hereditary transthyretin-mediated amyloidosis (hATTR).
• Patient Experience: The treatment has accumulated over 8,000 patient-years of experience worldwide, marking it as the first RNAi therapeutic approved for these conditions.

About Alnylam Pharmaceuticals

• Company Overview: Alnylam Pharmaceuticals is a leader in RNAi therapeutics, focusing on innovative medicines for rare and prevalent diseases. The company continues to advance its pipeline and aims to transform patient care through sustainable innovation.