ALNY News & Events

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.

Alnylam presented pooled Phase 2 safety data for zilebesiran, an investigational RNAi therapeutic being evaluated for cardiovascular risk reduction in patients with hypertension, with the potential to provide continuous control of blood pressure. The results support continued evaluation of zilebesiran in patients with hypertension and high CV risk in ZENITH, a global Phase 3 Cardiovascular Outcomes Trial that was initiated in September 2025. Building on the efficacy and safety results of the KARDIA Phase 2 program, these data reinforce the rationale for evaluating zilebesiran in patients with hypertension and established or at high risk of CVD, despite the use of at least two or more antihypertensives, in ZENITH. By targeting liver-expressed angiotensinogen, the most upstream precursor in the renin-angiotensin-aldosterone system, zilebesiran has the potential to provide continuous control of blood pressure with biannual dosing, offering a potentially differentiated approach to hypertension and CV risk management in patients with the highest unmet need. Pooled Safety Analysis from Phase 2 Studies A comprehensive analysis of safety across the Phase 2 KARDIA program demonstrated an acceptable safety profile for zilebesiran, both as monotherapy and in combination with standard-of-care antihypertensives, across patients with mild-to-moderate hypertension, those at high CV risk, or with lower eGFR at baseline. In the analysis, clinically relevant safety events, such as hypotension, hyperkalemia, and eGFR decline, were low across the patient populations, including those receiving zilebesiran in combination with an angiotensin-converting enzyme inhibitor or an angiotensin II receptor blocker. As previously reported, the majority of these events were transient and resolved without intervention.

Alnylam Pharmaceuticals announced a set of strategic efforts designed to accelerate earlier recognition and improve care coordination for patients with the cardiomyopathy of wild-type or hereditary transthyretin-mediated amyloidosis, ATTR-CM. Through complementary initiatives with Viz.ai and the American Heart Association, Alnylam is advancing a comprehensive, system-level approach to address persistent challenges of underdiagnosis and fragmented care in ATTR-CM. The collaboration includes the AI-Enhanced Echocardiography Workflow to Advance Recognition and Diagnosis of Cardiac Amyloidosis study. The initiative will launch at five pilot health systems later this year.