Amvuttra (vutrisiran) / Alnylam, Sanofi - LARVOL DELTA

Royalty Pharma acquires AMVUTTRA royalty for $310 million (Streetinsider.com) - "The transaction covers AMVUTTRA sales beginning October 1, 2025, excluding fixed payments from the original Blackstone investment of $70 million....projects sales to exceed $6 billion by 2028."

Commercial • Sales projection • Amyloidosis • Cardiomyopathy

Vutrisiran Healthcare Resource Utilization, Costs, Discontinuation, and Mortality: a Retrospective Database Analysis (AHA 2025) - "One-third to half of pts presented to the hospital within 1.5 y of vutrisiran treatment (before ATTR-CM approval); within 12 mo, roughly 1 in 4 died or discontinued therapy for ≥90 d past the 90-d administration schedule, with many switching to other ATTR treatments. This suggests that vutrisiran-treated pts continue to experience significant HCRU and costs related to disease progression despite treatment. A need remains for new therapies to further reduce burden and costs."

HEOR • Retrospective data • Amyloidosis • Cardiac Amyloidosis • Cardiomyopathy • Cardiovascular • CNS Disorders

Transthyretin Cardiac Amyloidosis Evaluation and Management: 2025 ACC Concise Clinical Guidance. (PubMed, J Am Coll Cardiol) - "Finally, individuals with transthyretin amyloid cardiomyopathy have benefitted from advances in broadly effective heart failure therapies, namely mineralocorticoid receptor antagonists and sodium glucose-cotransporter 2 inhibitors, as well as specific disease-modifying therapies with transthyretin stabilizers, tafamidis and acoramidis, and the transthyretin silencer vutrisiran. The purpose of this Concise Clinical Guidance is to offer updated strategies to clinicians, reflecting the expanding therapeutic landscape, and reinforcing best practices for the diagnosis and management of transthyretin amyloid cardiomyopathy with a focus on choice of disease-modifying therapies, heart failure therapies, and future directions."

Clinical guideline • Journal • Amyloidosis • Atrial Fibrillation • Cardiac Amyloidosis • Cardiomyopathy • Cardiovascular • CNS Disorders • Congestive Heart Failure • Heart Failure • Musculoskeletal Diseases • Musculoskeletal Pain • Orthopedics • Pain • Transplantation

LS.01: Introduction to AMVUTTRA® (vutrisiran) (AHA 2025) - "Description: Join our distinguished faculty as they review the clinical profile of AMVUTTRA for the treatment of the cardiomyopathy of transthyretin-mediated amyloidosis (ATTR-CM) in adults.Sponsored By: Alnylam Pharmaceuticals, Inc.This event is not part of the official Scientific Sessions Conference 2025 as planned by the American Heart Association Committee on Scientific Sessions Programming"

Amyloidosis • Cardiomyopathy • Cardiovascular

Comparative Efficacy and Safety of Vutrisiran, Acoramidis, Tafamidis in Transthyretin Amyloid Cardiomyopathy: A Network Meta-Analysis (AHA 2025) - "Background: Transthyretin amyloid cardiomyopathy (ATTR-CM) is a progressive, life-threatening disorder caused by transthyretin deposition in cardiac tissue. Vutrisiran demonstrated the most consistent survival and biomarker benefits, while Patisiran ranked highest in overall efficacy. Acoramidis showed strong improvement in functional capacity but varied across domains."

Retrospective data • Amyloidosis • Cardiac Amyloidosis • Cardiomyopathy • Cardiovascular

CA.APB.01: Electrophysiology, Amyloidosis & Precision Cardiology (AHA 2025) - "Several studies examine drug safety and efficacy (e.g., tafamidis, acoramidis, vutrisiran), while others investigate mechanisms of cardiac development, pacing strategies, and novel therapeutic approaches like gene transfer. This is not a CE accredited session. Poster Professor: Stavros Stavrakis (UNIVERSITY OF OKLAHOMA)"

Amyloidosis • Cardiac Amyloidosis • Cardiomyopathy • Cardiovascular • Congestive Heart Failure • Gene Therapies • Heart Failure • Infectious Disease • Novel Coronavirus Disease

Vutrisiran Improved Outcomes Versus Placebo in Patients with Transthyretin Amyloidosis with Cardiomyopathy and Severe Chronic Kidney Disease: Post Hoc Analysis of HELIOS-B (AHA 2025) - P3 | "Outcomes were assessed overall and by baseline tafamidis use (monotherapy and baseline tafamidis subgroups). Median (IQR) eGFR at baseline in pts receiving vutrisiran and PBO was 64 (50–81) and 65 (53–81) mL/min/1.73m2, respectively. Vutrisiran appeared to preserve renal function in pts with ATTR-CM. Consistent with results from the overall population, vutrisiran reduced the risk of ACM and CV events vs PBO in pts with ATTR-CM and advanced CKD in HELIOS-B; results require corroboration in a larger pt population."

Clinical • Retrospective data • Amyloidosis • Cardiac Amyloidosis • Cardiomyopathy • Cardiovascular • Chronic Kidney Disease • Nephrology • Renal Disease

Right Ventricular Free Wall Strain and Clinical Outcomes in Transthyretin Amyloid Cardiomyopathy and Effect of Vutrisiran: the HELIOS-B Study (AHA 2025) - "The association of baseline RVFWS with ACM and recurrent CV events was investigated using a modified Andersen-Gill model, adjusted for age, sex, ATTR disease type, National Amyloidosis Centre (NAC) stage, RV fractional area change (FAC), and tricuspid annular systolic myocardial velocity (RV S'), and stratified by baseline tafamidis use and treatment assignment. RVFWS is markedly impaired among patients with ATTR-CM and is strongly and independently associated with higher risk of ACM and recurrent CV events. Consistent with its beneficial effects on other measures of cardiac structure and function, vutrisiran stabilized RVFWS at 30 months compared with worsening in the placebo group."

Clinical • Clinical data • Amyloidosis • Atrial Fibrillation • Cardiac Amyloidosis • Cardiomyopathy • Cardiovascular • Heart Failure

Left Atrial Reservoir Strain and Clinical Outcomes in Transthyretin Amyloid Cardiomyopathy: Insights from the HELIOS-B Trial on Vutrisiran Efficacy (AHA 2025) - "Associations of baseline LASr with all-cause mortality as well as all-cause mortality and recurrent CV events were evaluated using Poisson regression models adjusted for age, ATTR disease type, National Amyloidosis Centre (NAC) disease stage, atrial fibrillation/flutter, left atrial volume index, LVEF, baseline tafamidis use and treatment assignment. Impairment in LASr is common among patients with ATTR-CM and is significantly and independently associated with all-cause mortality and recurrent CV events. Consistent with its beneficial effects on other measures of cardiac structure and function, vutrisiran attenuated worsening in LASr at 30 months compared with placebo. These findings support the central role of LA function in the pathophysiology of ATTR-CM."

Clinical • Clinical data • Amyloidosis • Atrial Fibrillation • Cardiac Amyloidosis • Cardiomyopathy • Cardiovascular

Association of TTR-Targeted Therapies with Cardiovascular Outcomes in Transthyretin Amyloid Cardiomyopathy: A Real-World Analysis (AHA 2025) - "Adults with a diagnosis of ATTR-CM were categorized into three groups based on prescription records: TTR stabilizers (e.g., tafamidis, acoramidis), TTR gene silencers (e.g., vutrisiran, eplontersen, patisiran, inotersen), or standard medical therapy. In this large, real-world analysis of patients with ATTR-CM, use of TTR stabilizers was associated with a lower incidence of major cardiovascular events compared with standard care. TTR gene silencers showed a similar directional association, though limited by a smaller sample size. These findings support further investigation in prospective studies to better understand the relationship between TTR-targeted therapies and clinical outcomes."

Clinical • Real-world • Real-world evidence • Amyloidosis • Cardiac Amyloidosis • Cardiomyopathy • Cardiovascular • Ventricular Tachycardia

Effects of Vutrisiran on Measures of Cardiac Structure, Function and Amyloid Burden by Cardiovascular Magnetic Resonance from the HELIOS-B Trial (AHA 2025) - "No patients received background tafamidis treatment. In patients with ATTR-CM, treatment with vutrisiran was associated with improvements in cardiac structure, function and amyloid burden compared to placebo."

Amyloidosis • Cardiac Amyloidosis • Cardiomyopathy • Cardiovascular

Ribonucleic acid and gene therapies in cardiovascular disease: clinical applications, delivery challenges and emerging precision tools. (PubMed, Heart) - "Recent European Medicines Agency and Food and Drug Administration-approved RNA therapies, including patisiran, vutrisiran and inclisiran, which employ lipid nanoparticle delivery systems, highlight the clinical potential of siRNAs for targeting hepatic molecular pathways. However, many challenges remain, particularly in targeting such therapies to cardiac tissues and optimising delivery systems. This review discusses the current state of the art in cardiovascular RNA and gene therapies, including current evidence, delivery challenges and the current landscape of gene and RNA therapies in phase I clinical trials and beyond."

Journal • Review • Cardiomyopathy • Cardiovascular • Gene Therapies

TRITON-PN: A Study to Evaluate the Efficacy and Safety of Nucresiran in Patients With Hereditary Transthyretin Amyloidosis With Polyneuropathy (clinicaltrials.gov) - P3 | N=125 | Not yet recruiting | Sponsor: Alnylam Pharmaceuticals

New P3 trial • Amyloidosis • Cardiac Amyloidosis • Pain

Total TTR: AMVUTTRA (vutrisiran) & ONPATTRO (patisiran) (Businesswire) - "Achieved global net product revenues for AMVUTTRA and ONPATTRO for the third quarter of $685 million and $39 million, respectively, representing $724 million in total TTR net product revenues and 135% total TTR growth compared to Q3 2024."

Sales • Amyloidosis • Cardiomyopathy

Efficacy and safety of vutrisiran in transthyretin amyloid cardiomyopathy across the age spectrum: The HELIOS-B trial. (PubMed, Eur J Heart Fail) - "Vutrisiran reduced all-cause mortality and cardiovascular events and maintained function and quality of life in patients with ATTR-CM across the age spectrum, including those ≥80 years."

Journal • Amyloidosis • Cardiac Amyloidosis • Cardiomyopathy • Cardiovascular

Clinical and radiological stabilization following vutrisiran treatment in transthyretin leptomeningeal amyloidosis: a case report. (PubMed, Amyloid) - No abstract available

Journal • Amyloidosis

Cardiac Amyloidosis: Tribulations and New Frontiers. (PubMed, J Pers Med) - "Critically, it is imperative that physicians develop close relationships with the patient that addresses not only their individual health needs but also their unique psychosocial situation. Therefore, more clinical trials, protocols and patient resources are needed to better inform and guide providers managing these complex patient needs."

Journal • Review • Amyloidosis • Cardiac Amyloidosis • Cardiomyopathy • Cardiovascular • Congestive Heart Failure • Heart Failure • Transplantation

EFFICACY OF VUTRISIRAN IN PATIENTS WITH HEREDITARY TRANSTHYRETIN-MEDIATED AMYLOIDOSIS WITH POLYNEUROPATHY: ANALYSIS OF THE EAST ASIAN SUBPOPULATION FROM THE HELIOS-A STUDY (WCN 2025) - P3 | "Data in the HELIOS-A East Asian population were consistent with those from the overall HELIOS-A population and indicate a notable health benefit for vutrisiran treatment in East Asian patients with ATTRv amyloidosis and polyneuropathy."

Clinical • CNS Disorders • Pain

Disease-Modifying Therapies for Transthyretin Amyloid Cardiomyopathy: A Systematic Review and Meta-Analysis. (PubMed, Arq Bras Cardiol) - "TTR stabilizers significantly reduced all-cause mortality and hospitalizations in patients with ATTR-CM compared with placebo. These benefits were not observed with TTR silencers, potentially due to shorter follow-up durations in the studies evaluated. Both therapies improved functional status and serum levels of NT-proBNP."

Biomarker • Clinical • Journal • Retrospective data • Review • Amyloidosis • Cardiac Amyloidosis • Cardiomyopathy • Cardiovascular

A Rare Unusually Aggressive Form of Hereditary Transthyretin Amyloidosis. (PubMed, JACC Case Rep) - "Understanding the phenotype associated with this ATTRv genotype, along with the patient's family history, guided targeted and timely evaluation and treatment."

Journal • Amyloidosis • Cardiac Amyloidosis • Cardiomyopathy • Cardiovascular • Congestive Heart Failure • Gastrointestinal Disorder • Heart Failure • Pain

Vutrisiran improves cardiac structure and function in individuals with transthyretin amyloidosis with cardiomyopathy. (PubMed, Nat Cardiovasc Res) - No abstract available

Journal • Amyloidosis • Cardiac Amyloidosis • Cardiomyopathy • Cardiovascular

Advances in Cardiovascular Pharmacotherapy. V. Molecular Targets in Transthyretin Amyloid Cardiomyopathy. (PubMed, J Cardiothorac Vasc Anesth) - "These groundbreaking advances are transforming ATTR-CM from debilitating, uniformly fatal disease to a manageable chronic condition with extended life-expectancy and preserved quality of life. This review discusses the pathophysiology of ATTR-CM, reviews the clinical trials demonstrating the efficacy of drugs that stabilize transthyretin or silence its expression, describes the preliminary use of monoclonal antibodies to degrade amyloid fibrils and reverse the disease's structural and functional consequences, and lastly, comments on the potential anesthetic implications of these new disease-modifying therapies."

Journal • Review • Amyloidosis • Anesthesia • Cardiac Amyloidosis • Cardiomyopathy • Cardiovascular • Congestive Heart Failure • Heart Failure

IET 07 Industry Expert Theaters (No CEUs) - Introduction to AMVUTTRA® (vutrisiran) (HFSA 2025) - "Sponsored by Alnylam This activity does not offer CEUs. Join our distinguished faculty as they review the clinical profile of AMVUTTRA for the treatment of the cardiomyopathy of transthyretin-mediated amyloidosis (ATTR-CM) in adults Faculty Rola Khedraki, MDAdvanced Heart Failure and Transplant CardiologistScripps Clinic John R. Anderson Medical PavilionLa Jolla, CA Dmitry Yaranov, MDAdvanced Heart Failure and Transplant CardiologistBaptist Medical GroupGermantown, TN"

Amyloidosis • Cardiomyopathy • Cardiovascular • Congestive Heart Failure • Heart Failure

Introduction to AMVUTTRA® (vutrisiran) - Speaker (HFSA 2025) - "Sponsored by Alnylam"

Introduction to AMVUTTRA® (vutrisiran) - Speaker (HFSA 2025) - "Sponsored by Alnylam"