Amvuttra (vutrisiran) / Alnylam, Sanofi - LARVOL DELTA

Vutrisiran in ATTR-CM: transforming outcomes with precision medicine (ESC-WCC 2025) - "Sponsored by Alnylam Pharmaceuticals"

Cardiovascular

RNAi therapeutics: changing the future landscape in ATTR-CM management (ESC-WCC 2025) - "Strengthen cardiologists' understanding of the clinical profile of vutrisiran for the treatment of ATTR-CM...This symposium is sponsored/funded by Alnylam Pharmaceuticals. May contain information on Alnylam medicinal products"

Cardiovascular

A new chapter in transthyretin amyloid cardiomyopathy (ATTR-CM): what comes next in clinical practice? (ESC-WCC 2025) - "Amvuttra® no está autorizado en España para la indicación ATTR con cardiomiopatía.This is an Alnylam-sponsored promotional symposium; organised and funded by Alnylam Pharmaceuticals. It may contain information on Alnylam medicinal products; AMV-ESP-00185; May 2025"

Clinical • Cardiac Amyloidosis • Cardiomyopathy • Cardiovascular

Effects of vutrisiran on echocardiographic measures of cardiac structure and function: the HELIOS-B trial (ESC-WCC 2025) - "Joint session with Nature Medicine"

Cardiovascular

Optimizing treatment strategies for transthyretin amyloid cardiomyopathy: a comprehensive Bayesian network meta-analysis of disease-specific therapies (ESC-WCC 2025) - "Emerging disease-specific therapies, including tafamidis, patisiran, acoramidis, and vutrisiran, have shown promise in improving clinical outcomes. This study highlights the differential benefits of disease-specific therapies in ATTR-CM. patisiran was most effective for mortality reduction, acoramidis for cardiovascular hospitalizations, patisiran for functional capacity, and tafamidis for quality of life. Treatment selection should be individualized based on mortality risk, functional capacity, and quality of life to optimize ATTR-CM management."

Retrospective data • Cardiac Amyloidosis • Cardiomyopathy • Cardiovascular

Relative efficacy of tafamidis, acoramidis, patisiran and vutrisiran in patients with transthyretin cardiac amyloidosis: a network meta-analysis (ESC-WCC 2025) - "Tafamidis demonstrated the highest efficacy in improving survival, reducing cardiovascular hospitalizations, and enhancing functional capacity and quality of life in patients with ATTR-CA, qualifying as the primary treatment choice. Vutrisiran and acoramidis emerged as viable alternatives."

Retrospective data • Cardiac Amyloidosis • Cardiomyopathy • Cardiovascular • Congestive Heart Failure • Heart Failure

RNA interference therapy in transthyretin amyloid cardiomyopathy: a systematic review and meta-analysis of randomised controlled trials (ESC-WCC 2025) - "In this meta-analysis of randomised controlled trials, RNAi therapeutics, patisiran and vutrisiran, significantly reduced serum transthyretin levels and improved quality of life and imaging parameters in ATTR-CM. These findings suggest the potential of these agents to slow disease progression. Further RCTs are warranted to assess the long-term effects of this therapy."

Retrospective data • Review • Cardiac Amyloidosis • Cardiomyopathy • Cardiovascular • Congestive Heart Failure • Heart Failure

HELIOS-B: 12-month results from the open-label extension period of vutrisiran in patients with transthyretin amyloidosis with cardiomyopathy (ESC-WCC 2025) - "Over the 33–36-month (M), double-blind (DB) period of HELIOS-B, vutrisiran treatment lowered the risk of the primary composite endpoint of all-cause mortality (ACM) and recurrent cardiovascular (CV) events vs placebo in both the overall population and the monotherapy population (patients not on tafamidis at baseline). During the DB period of HELIOS-B, vutrisiran demonstrated significant clinical benefit versus placebo in patients with ATTR-CM. The impact of early vs delayed initiation of vutrisiran in this population will be elucidated in the OLE M12 data."

Clinical • Cardiac Amyloidosis • Cardiomyopathy • Cardiovascular

Vutrisiran reduces days lost to death and/or hospitalization versus placebo in patients with transthyretin amyloidosis with cardiomyopathy in the HELIOS-B trial [WITHDRAWN] (ESC-WCC 2025) - No abstract available

Clinical • Cardiac Amyloidosis • Cardiomyopathy • Cardiovascular

ATTRv longevity variant: a novel clinical entity in the spectrum of cardiac amyloidosis (ESC-WCC 2025) - "Among ATTRv patients, genetic testing enabled targeted therapy in 11 individuals (9 patisiran, 2 vutrisiran). Up to 15% of elderly patients with ATTR-CM carry a pathogenic TTR mutation, with Ile88Leu being the most prevalent in central Italy. This late-onset ATTRv exhibits a distinct phenotype, differing from younger-onset ATTRv, with higher female prevalence, increased neuropathy, lower arrhythmic burden, and reduced bone scintigraphy positivity, defining a novel entity: the "ATTRv Longevity Variant." These findings support systematic genetic testing in all ATTR-CM patients, irrespective of age, to enable targeted therapy and early intervention in at-risk relatives."

Clinical • Cardiac Amyloidosis • Cardiomyopathy • Cardiovascular

Vutrisiran in Transthyretin Amyloidosis: A Pooled Safety Analysis of HELIOS-A and HELIOS-B. (PubMed, JACC Adv) - "In a broad population of patients with ATTR who were treated for up to 58 months, vutrisiran was well tolerated and had an acceptable safety profile, consistent with that previously reported for the HELIOS-A and HELIOS-B studies."

Journal • Amyloidosis • Cardiac Amyloidosis • Cardiomyopathy • Cardiovascular • Congestive Heart Failure • Heart Failure • Infectious Disease • Novel Coronavirus Disease • Pain

Effects of Vutrisiran on Cardiac Function and Outcomes in Patients With Transthyretin Amyloidosis With Cardiomyopathy. (PubMed, J Am Coll Cardiol) - "Echocardiographic measures of biventricular systolic and diastolic function provide important prognostic information beyond National Amyloidosis Centre stage in patients with ATTR-CM. Vutrisiran improved diastolic function and attenuated declines in left ventricular and right ventricular systolic function over 18 months. The benefits on cardiac function with vutrisiran may partly underlie its beneficial effects on clinical outcomes."

Clinical • Journal • Amyloidosis • Cardiac Amyloidosis • Cardiomyopathy • Cardiovascular

Cardiac Biomarkers as an Early Warning System in Transthyretin Cardiac Amyloidosis. (PubMed, J Am Coll Cardiol) - No abstract available

Biomarker • Journal • Amyloidosis • Cardiac Amyloidosis • Cardiomyopathy • Cardiovascular

Alnylam’s Amvuttra approved by MHRA to treat rare heart disease ATTR-CM (PMLive) - "Alnylam Pharmaceuticals’ Amvuttra (vutrisiran) has been approved by the Medicines and Healthcare products Regulatory Agency (MHRA) to treat adults with transthyretin amyloid cardiomyopathy (ATTR-CM), a rare and potentially fatal disease of the heart muscle....The UK regulator’s decision was supported by results from the late-stage HELIOS-B study, in which Amvuttra was associated with significant reductions in mortality and cardiovascular events in ATTR-CM patients."

MHRA approval • Amyloidosis • Cardiomyopathy • Cardiovascular

Intracellular fatty acid levels differentially impact target silencing by FDA-approved siRNA drugs. (PubMed, Biochem Pharmacol) - "Efficacy in the reduction of targets at both the mRNA and protein levels was determined for three selected Food and Drug Administration (FDA)-approved siRNA drugs, patisiran, vutrisiran, and inclisiran. Our findings demonstrate strong evidence that elevated intracellular FFA levels significantly alter the efficacy of the FDA-approved siRNA drugs, impacting both mRNA and protein target reduction and highlighting a previously underexplored factor which could impact clinical outcomes. Understanding the impact on siRNA functions is critical for optimizing the therapeutic potential of siRNA-based treatments for patients with FFA diseases, such as obesity and MAFLD."

FDA event • Journal • Genetic Disorders • Hepatology • Metabolic Dysfunction-Associated Steatotic Liver Disease • Obesity

Effects of vutrisiran on cardiac structure and function in patients with transthyretin amyloidosis with cardiomyopathy: secondary outcomes of the HELIOS-B trial. (PubMed, Nat Med) - P3 | "Consistent with its clinical benefits, these echocardiographic findings indicate favorable effects of vutrisiran on cardiac structure and function in patients with ATTR-CM. ClinicalTrials.gov registration: NCT04153149 ."

Clinical • Journal • Amyloidosis • Cardiac Amyloidosis • Cardiomyopathy • Cardiovascular

A mutation in transthyretin gene in a Mexican patient leading to hereditary amyloidosis: a case report. (PubMed, J Med Case Rep) - "A high index of suspicion is required for diagnosing transthyretin amyloidosis. This case will help raise awareness among physicians regarding the presence of the G67A mutation in Mexican patients and its management."

Journal • Amyloidosis • Cardiac Amyloidosis • Cardiovascular • Congestive Heart Failure • Heart Failure • Pain

Impact of Vutrisiran on Cardiac Biomarkers in Patients With Transthyretin Amyloidosis With Cardiomyopathy From HELIOS-B. (PubMed, J Am Coll Cardiol) - P3 | "Patterns of associations between biomarkers and adverse outcomes support the importance of early treatment initiation and the potential for risk reduction in patients with ATTR-CM. Vutrisiran maintained stable or reduced levels of both biomarkers consistent with the benefit of treatment in reducing the risk of cardiovascular events and all-cause mortality. (HELIOS-B: A Study to Evaluate Vutrisiran in Patients With Transthyretin Amyloidosis With Cardiomyopathy; NCT04153149)."

Biomarker • Clinical • Journal • Amyloidosis • Cardiac Amyloidosis • Cardiomyopathy • Cardiovascular • Developmental Disorders

Effects of vutrisiran on cardiac structure and function in patients with transthyretin amyloidosis with cardiomyopathy: secondary outcomes of the HELIOS-B trial (Nature) - P3 | N=655 | HELIOS-B (NCT04153149) | Sponsor: Alnylam Pharmaceuticals | "At 30 months after treatment, as compared to the placebo group, vutrisiran treatment attenuated increases in mean left ventricular (LV) wall thickness (least squares mean difference: −0.4 mm; 95% confidence interval (CI): −0.8, 0.0; P = 0.03) and LV mass index (−10.6 g m−2; 95% CI: −18.0, −3.3; P < 0.01). Vutrisiran treatment also attenuated declines in LV ejection fraction (2.0%; 95% CI: 0.3, 3.7; P = 0.02), absolute global longitudinal strain (1.2%; 95% CI: 0.7, 1.7; P < 0.01) and LV stroke volume (4.1 ml; 95% CI: 1.7, 6.4; P < 0.01), and decreased both the average ratio of early diastolic transmitral flow velocity to early diastolic mitral annular tissue velocity..."

P3 data • Amyloidosis • Cardiomyopathy

Alnylam to Present Progress in Transforming the Treatment of Cardiovascular Disease with RNAi Therapeutics at European Society of Cardiology Congress 2025 (Businesswire) - "Data from the Company’s flagship TTR franchise will also be presented, including new analyses from the HELIOS-B Phase 3 study of AMVUTTRA (vutrisiran), which delivers rapid knockdown of transthyretin, in patients with ATTR amyloidosis with cardiomyopathy (ATTR-CM). These presentations include results of 12-month follow-up from the ongoing open-label extension (OLE) period of HELIOS-B, which will provide further insights into the sustained longer-term benefits of treatment with AMVUTTRA, and an analysis examining the effect of AMVUTTRA on days lost to death and/or hospitalization (DLDH)."

P3 data • Amyloidosis • Cardiomyopathy

Structure, Function, and Outcomes in Transthyretin Amyloid Cardiomyopathy: Insights From HELIOS-B. (PubMed, J Am Coll Cardiol) - No abstract available

Journal • Amyloidosis • Cardiac Amyloidosis • Cardiomyopathy • Cardiovascular

Novel Therapeutic Mechanisms for the Treatment of Transthyretin Amyloid Cardiomyopathy. (PubMed, Cardiol Rev) - "In this review, special attention is given to tafamidis and vutrisiran for the treatment of ATTR-CM, while exploring the therapeutic potential of leptin modulation and TIE kinase inhibition through a narrative review of preclinical and clinical evidence. On the other hand, leptin modulators and TIE kinase inhibition show promise in clinical trials, but further validation of these findings is necessary. Ultimately, these agents may become therapeutic targets for treating ATTR-CM in the future."

Journal • Amyloidosis • Cardiac Amyloidosis • Cardiomyopathy • Cardiovascular • LEP

Second Quarter 2025 and Recent Significant Business Highlights (Businesswire) - "Achieved global net product revenues for AMVUTTRA and ONPATTRO for the second quarter of $492 million and $53 million, respectively, representing $544 million in total TTR net product revenues and 77% total TTR growth compared to Q2 2024; Achieved approximately 1,400 ATTR-CM patients on AMVUTTRA as of June 30, 2025....Alnylam announces today that nucresiran has received Fast Track Designation from the FDA's Division of Cardiology and Nephrology for the treatment of the cardiomyopathy of wild-type or hereditary transthyretin mediated amyloidosis in adults to reduce mortality, cardiovascular hospitalizations, and urgent heart failure visits."

Fast track • Sales • Amyloidosis • Cardiomyopathy

Realizing the therapeutic potential of rapid knockdown of transthyretin via RNA interference in transthyretin amyloidosis. (PubMed, Mol Ther Nucleic Acids) - "This review describes the clinical development of patisiran and vutrisiran, which target the hepatic production of TTR for the treatment of ATTR amyloidosis. Findings from clinical studies show that rapid knockdown of TTR by RNAi therapeutics initiates a cascade of effects that ultimately leads to benefits across multiple clinical, quality of life, imaging, and biomarker disease measures of ATTR amyloidosis disease progression."

Journal • Review • Amyloidosis • Cardiac Amyloidosis • Cardiovascular

Transthyretin Amyloid Cardiomyopathy-2025 Update: Current Diagnostic Approaches and Emerging Therapeutic Options. (PubMed, J Clin Med) - "First-generation therapies such as tafamidis have demonstrated survival benefits in ATTR-CM. More recently, second-generation agents-such as the TTR stabilizer acoramidis and RNA silencers including vutrisiran and eplontersen-have shown promising efficacy in clinical trials...This review outlines current diagnostic strategies and therapeutic options for ATTR amyloidosis, emphasizing the need for early detection and individualized treatment approaches. The expanding therapeutic landscape highlights the importance of accurate phenotyping and timely intervention to optimize clinical outcomes."

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