Amvuttra (vutrisiran) / Alnylam, Sanofi - LARVOL DELTA

HELIOS-A: A Study of Vutrisiran (ALN-TTRSC02) in Patients With Hereditary Transthyretin Amyloidosis (hATTR Amyloidosis) (clinicaltrials.gov) - P3 | N=164 | Active, not recruiting | Sponsor: Alnylam Pharmaceuticals | Trial completion date: Oct 2026 ➔ Oct 2025

Trial completion date • Amyloidosis • Cardiac Amyloidosis

Hypertrophic Cardiomyopathy and Phenocopies: New Therapies for Old Diseases-Current Evidence and Future Perspectives. (PubMed, J Clin Med) - "In particular, many chemotherapy agents (alkylating agents, proteasome inhibitors, immunomodulatory drugs, and monoclonal antibodies targeting clonal cells) allowing one to treat AL amyloidosis, transthyretin stabilizers (tafamidis and acoramidis), and gene silencers (patisiran and vutrisiran) are available in transthyretin cardiac amyloidosis, and enzyme replacement therapies (agalsidase-alpha, agalsidase-beta, and pegunigalsidase-alpha) or oral chaperone therapy (migalastat) can be used in Anderson-Fabry disease. In addition, the introduction of cardiac myosin inhibitors (mavacamten and aficamten) has deeply modified the treatment of hypertrophic obstructive cardiomyopathy. The aim of this review is to describe the new disease-modifying treatments available in HCM and phenocopies in light of current scientific evidence."

Journal • Review • Amyloidosis • Cardiac Amyloidosis • Cardiomyopathy • Cardiovascular • Fabry Disease • Gene Therapies • Genetic Disorders • Hypertrophic Cardiomyopathy • Obstructive Hypertrophic Cardiomyopathy • Rare Diseases

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

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

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

Cardiovascular

Relative efficacy of tafamidis, acoramidis, patisiran and vutrisiran in patients with transthyretin cardiac amyloidosis: a network meta-analysis (ESC-WCC 2025) - No abstract available

Retrospective data • Cardiac Amyloidosis • Cardiovascular

HELIOS-B: 12-month results from the open-label extension period of vutrisiran in patients with transthyretin amyloidosis with cardiomyopathy (ESC-WCC 2025) - No abstract available

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 (ESC-WCC 2025) - No abstract available

Clinical • Cardiac Amyloidosis • Cardiomyopathy • Cardiovascular

Vutrisiran (Amvuttra) for transthyretin amyloid cardiomyopathy. (PubMed, Med Lett Drugs Ther) - No abstract available

Journal • Amyloidosis • Cardiac Amyloidosis • Cardiomyopathy • Cardiovascular

EC approves first RNAi therapy for ATTR cardiomyopathy (Investing.com) - "Alnylam Pharmaceuticals, Inc...announced today that the European Commission (EC) has granted approval for its RNAi therapeutic, AMVUTTRA (vutrisiran), to treat adult patients with wild-type or hereditary transthyretin amyloidosis with cardiomyopathy (ATTR-CM)....The approval is based on results from the HELIOS-B Phase 3 study, which demonstrated up to a 36% reduction in all-cause mortality and improvements in functional capacity and quality of life with just four quarterly doses per year."

EMA approval • Amyloidosis • Cardiac Amyloidosis • Cardiomyopathy

Pharmacological Management of Transthyretin Amyloid Cardiomyopathy: Where We Are and Where We Are Going. (PubMed, J Clin Med) - "TTR stabilizers, such as tafamidis and acoramidis, can reduce TTR instability and subsequent amyloid fibril formation...Gene-silencing therapies using small interfering RNAs (siRNAs), such as patisiran and vutrisiran, or antisense oligonucleotide inhibitors (ASOs), such as inotersen and eplontersen, serve as powerful therapeutic options by decreasing TTR production; trials on patients with ATTR-CM have been recently published or are ongoing. Novel, emerging therapies aim to enhance fibril clearance using monoclonal antibodies, such as NI006, that target amyloid deposits in the myocardium, promoting their depletion, plausibly with regression of the structural and functional impairments caused by the disease...Future directions will involve improving patients' screening to achieve earlier diagnoses, optimising patients' selection for disease-modifying therapy and identifying criteria for the treatment's response or lack thereof to possibly consider therapy..."

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

Current and emerging treatment options for transthyretin amyloid cardiomyopathy. (PubMed, Heart) - "Treatments available in clinical practice include TTR stabilisers (tafamidis and acoramidis), which prevent the dissociation of TTR tetramer into monomers and oligomers that subsequently form amyloid fibrils, and gene-silencing therapies (patisiran, inotersen and vutrisiran), which suppress the hepatic synthesis of TTR, which is the amyloid precursor protein. Novel treatment strategies that are at various stages of development include Clustered Regularly Interspaced Short Palindromic Repeats-Cas9 gene-editing technology (nexiguran ziclumeran), which, if successful, offers the prospect of a single-dose treatment, and monoclonal (cormitug and ALXN220) and pan-amyloid antibodies (AT-02) that seek to target and remove amyloid fibrils that have deposited in the myocardium...The success of ATTR-specific disease-modifying therapies has already altered the treatment landscape and changed the perception of ATTR amyloidosis from a progressive and fatal disease to one that is..."

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

Impact of Vutrisiran on Functional Capacity and Quality of Life in ATTR Cardiomyopathy: HELIOS-B Analysis. (PubMed, J Am Coll Cardiol) - No abstract available

HEOR • Journal • Cardiomyopathy • Cardiovascular

Differential Protein Precipitation-Based GalNAc-siRNA Sample Preparation with LC/MS Method Development Workflow in Plasma. (PubMed, Anal Chem) - "This approach achieved a lower limit of quantification in the single-digit ng/mL range for four FDA-approved GalNAc-siRNAs (Givosiran, Lumasiran, Inclisiran, and Vutrisiran) and a major Givosiran metabolite, AS(N-1)3'. The applicability of this approach was successfully demonstrated by analyzing plasma samples from an in vivo rat study involving three molecules (Givosiran, Givosiran AS(N-1)3', and Inclisiran). This method is straightforward, robust, highly sensitive, and cost-effective and should be readily adaptable for the bioanalysis of diverse GalNAc-siRNAs and, potentially, for late-stage sample analyses."

Journal

HELIOS-B: Vutrisiran reduces all-cause mortality (HEART FAILURE 2025) - No abstract available

Late-breaking abstract • Cardiovascular

Vutrisiran in patients with transthyretin amyloidosis with cardiomyopathy in HELIOS-B who had progressed on tafamidis (HEART FAILURE 2025) - P3 | "In this post-hoc subgroup analysis of HELIOS-B, patients with ATTR progression under tafamidis presented / experienced a favorable trend in reducing incidence of composite ACM with recurrent CV events with vutrisiran treatment."

Clinical • Cardiac Amyloidosis • Cardiomyopathy • Cardiovascular • Congestive Heart Failure • Heart Failure

Relative efficacy of tafamidis, acoramidis, patisiran and vutrisiran in patients with transthyretin cardiac amyloidosis: a network meta-analysis (HEART FAILURE 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

Design and rationale of a phase 3 study to evaluate the efficacy and safety of nucresiran (ALN-TTRsc04) in patients with transthyretin amyloidosis with cardiomyopathy (HEART FAILURE 2025) - "Most recently, vutrisiran was shown to improve outcomes for patients with ATTR-CM across multiple domains in the HELIOS-B study, including reducing cardiovascular events and all-cause mortality, and improving functional capacity and quality of life (3). The phase 3 study will investigate the efficacy, safety and PK/PD of nucresiran in patients with ATTR-CM. Nucresiran has the potential to provide greater and more sustained TTR knockdown with lower inter-patient variability and less frequent dosing than current TTR-lowering therapies."

Clinical • P3 data • Cardiac Amyloidosis • Cardiomyopathy • Cardiovascular

Treatment with vutrisiran in people with transthyretin amyloidosis with cardiomyopathy: a plain language summary. (PubMed, Future Cardiol) - No abstract available

Journal • Amyloidosis • Cardiac Amyloidosis • Cardiomyopathy • Cardiovascular

Alnylam will present the study design and rationale for TRITON-CM, a Phase 3, randomized, double-blind, study of nucresiran in patients with ATTR-CM. (Businesswire) - "The study is on track to initiate in the first half of 2025 and will enroll approximately 1,200 patients with wild-type or variant TTR and confirmed cardiomyopathy, including those receiving background stabilizer therapy. Additional details of the study’s secondary endpoints and key inclusion and exclusion criteria will be shared on Monday, May 19...The Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) has adopted a positive opinion recommending the approval of vutrisiran for [cardiomyopathy of wild-type or hereditary transthyretin-mediated amyloidosis]. A formal regulatory decision by the European Commission of the EMA is expected by the third quarter of 2025...Alnylam remains on track to proceed with additional global regulatory submissions for vutrisiran in 2025 and beyond."

Clinical protocol • EMA approval • Filing • New trial • Amyloidosis • Cardiomyopathy

AMVUTTRA (vutrisiran) Significantly Reduces Mortality and a Range of Important Cardiovascular Events in Patients with ATTR Amyloidosis with Cardiomyopathy: Additional Data from HELIOS-B (Businesswire) - P3 | N=655 | HELIOS-B (NCT04153149) | Sponsor: Alnylam Pharmaceuticals | "Importantly, results from the November 2024 data cut, including further follow up through up to 42 months, reinforce the primary HELIOS-B analysis showing vutrisiran’s effect on ACM, and further demonstrate that vutrisiran reduces CV mortality. Through 42 months, the risk of ACM was reduced by 36% (95% CI: 0.46, 0.88; p = 0.007) and the risk of CV mortality was reduced by 33% (95% CI: 0.47, 0.96; p = 0.038) in the overall population, compared to placebo. For both the primary analysis and the current analysis, vital status through 42 months was ascertained for over 99% of all randomized patients from the HELIOS-B study, underscoring the robustness of the results."

P3 data • Amyloidosis • Cardiomyopathy

Vutrisiran Improves Survival and Reduces Cardiovascular Events in ATTR Amyloid Cardiomyopathy: HELIOS-B. (PubMed, J Am Coll Cardiol) - P3 | "Consistent with the primary trial results, vutrisiran reliably reduced the risk of ACM, CV mortality, CV hospitalizations, HF hospitalizations, and urgent HF visits vs placebo in patients with ATTR-CM. (HELIOS-B: A Study to Evaluate Vutrisiran in Patients With Transthyretin Amyloidosis With Cardiomyopathy; NCT04153149)."

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

Transthyretin Gene Silencing in Amyloid Transthyretin Cardiomyopathy: A Novel Treatment Delivers New Dilemmas. (PubMed, J Am Coll Cardiol) - No abstract available

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

Alnylam to Share Progress Across its Transthyretin Amyloidosis Franchise Including Additional Analyses of the HELIOS-B Phase 3 Study Results at Heart Failure 2025 Congress (Businesswire) - "Alnylam Pharmaceuticals, Inc...announced that the Company will present the latest data from its flagship transthyretin amyloidosis (TTR) franchise at the upcoming Heart Failure 2025 Congress, a scientific congress of the European Society of Cardiology, taking place May 17-20 in Belgrade, Serbia...The latest analyses of the HELIOS-B Phase 3 study of vutrisiran in patients with ATTR amyloidosis with cardiomyopathy (ATTR-CM), including further outcomes data on cardiovascular hospitalizations and urgent heart failure visits up to 42-months, will be presented as a late-breaking abstract....Additional updates to be presented include the design and rationale of the TRITON-CM Phase 3 study of nucresiran (ALN-TTRsc04), an investigational next-generation TTR silencer, in patients with ATTR-CM, as well as an additional analysis from the HELIOS-B study of vutrisiran in patients with ATTR-CM who experienced disease progression while being treated with tafamidis."

Clinical data • Clinical protocol • Amyloidosis • Cardiomyopathy

Vutrisiran in Patients with Transthyretin Amyloidosis with Cardiomyopathy. Reply. (PubMed, N Engl J Med) - No abstract available

Journal • Amyloidosis • Cardiac Amyloidosis • Cardiomyopathy • Cardiovascular