Alnylam Releases New Cardiovascular Data, Vutrisiran Significantly Improves Patient Quality of Life

Alnylam Pharmaceuticals announced new clinical and real-world data from its cardiovascular portfolio presented at the American College of Cardiology's Annual Scientific Session and Expo, reinforcing the potential of RNAi to deliver fundamentally differentiated, effective, and durable impact for patients living with cardiovascular disease . New data continue to support the use of vutrisiran as a first-line treatment for patients with the cardiomyopathy of wild-type or hereditary transthyretin-mediated amyloidosis. The HELIOS-B analyses demonstrate that vutrisiran delivered meaningful improvements in how patients with ATTR-CM feel and function, with benefits sustained across disease severity, reinforcing how TTR silencing at its source translates into durable clinical and health-related quality-of-life benefits for patients. New analyses expand the totality of HELIOS-B evidence demonstrating improvements in patients' health-related QoL, consistent efficacy on CV outcomes across a range of patient subgroups, including those with advanced disease and diastolic dysfunction, and real-world data showing high treatment adherence with four healthcare professional-administered doses per year. In addition to clinical studies, vutrisiran has more than 13,000 patient-years of experience for the treatment of ATTR-CM and the polyneuropathy of hereditary transthyretin-mediated amyloidosis in adults. This analysis evaluated placebo-corrected mean score changes of vutrisiran-treated patients across the 23-item Kansas City Cardiomyopathy Questionnaire Overall Summary Score from baseline to 30 Months. Compared to placebo, vutrisiran demonstrated improvements in nearly all components, most notably in physical limitations and QoL. Moreover, the magnitude of treatment effect in age-adjusted KCCQ-OSS favoring vutrisiran was comparable to the difference observed in patients 11 years apart in age. These findings were simultaneously published in the European Journal of Heart Failure. HELIOS-B Post Hoc Analysis of Patients with Advanced Disease During the Double-Blind Period: The analysis assessed the risk of patients developing advanced disease as defined by transitioning to New York Heart Association class III and National Amyloidosis Center stage 3, or NYHA class IV, with vutrisiran versus placebo during the HELIOS-B DB period. In the overall population, fewer patients receiving vutrisiran developed advanced disease compared to patients receiving placebo. The analysis also assessed the effect of vutrisiran on outcomes in patients with ATTR-CM who developed advanced disease. In these patients, treatment with vutrisiran reduced the risk of the composite of all-cause mortality and recurrent CV events during the DB period by 40% in the overall population and 46% in the monotherapy population, versus placebo. Treatment with vutrisiran also reduced the risk of ACM during the DB period plus up to six months of open-label extension by 56% in the overall population and 77% in the monotherapy population, versus placebo. Vutrisiran had a favorable safety profile in patients with advanced disease, with a similar or fewer proportion of patients experiencing adverse events, compared to placebo. A retrospective cohort study of real-world data in patients with amyloidosis indicated high adherence and persistence to vutrisiran treatment, with most patients still receiving treatment after 12 months. Patients were followed up for a mean of 613.8 days. Over the treatment period, 93.8% were adherent to vutrisiran, defined as PDC greater than or equal to0.8. Diastolic dysfunction is prognostic of poor outcomes in patients with ATTR-CM. To evaluate the effect of vutrisiran in patients across a range of diastolic dysfunction grades at baseline, a post hoc analysis of HELIOS-B assessed outcomes at Month 30 in patients who had evaluable DDG at baseline. Higher grade DDG at baseline corresponded with adverse outcomes in ATTR-CM. Vutrisiran was associated with a lower risk of worsening DDG, with a greater proportion of patients with baseline DDG III showing stable or improved NYHA class from baseline to Month 30 in the overall and monotherapy populations, compared to patients receiving placebo. Vutrisiran reduced the risk of ACM and CV events during the DB period, irrespective of baseline DDG.