Amvuttra (vutrisiran) / Alnylam, Sanofi - LARVOL DELTA

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

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

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

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

Journal • Amyloidosis • Cardiac Amyloidosis • Cardiomyopathy • Cardiovascular

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

Journal • Amyloidosis • Cardiac Amyloidosis • Cardiomyopathy • Cardiovascular

First Quarter 2025 and Recent Significant Business Highlights (Businesswire) - "Strong progress making AMVUTTRA available for ATTR-CM in various global markets....Received approval from ANVISA (Brazilian Health Regulatory Agency) for ATTR-CM."

Approval • Amyloidosis • Cardiomyopathy

Key Upcoming Events (Businesswire) - "Alnylam intends to initiate the TRITON-CM Phase 3 clinical trial of nucresiran in patients with ATTR-CM in the first half of 2025...Alnylam anticipates regulatory approval for AMVUTTRA for ATTR-CM in Japan in Q2 and in the European Union in Q3 of 2025...Alnylam also intends to release data from the KARDIA-3 Phase 2 clinical trial evaluating zilebesiran in combination with at least two antihypertensives in high cardiovascular risk patients with uncontrolled hypertension in the second half of 2025. These results will further inform the design of a Phase 3 cardiovascular outcomes trial for zilebesiran that Alnylam intends to initiate in the second half of 2025."

EMA approval • Japan approval • New P3 trial • P2 data • Amyloidosis • Cardiomyopathy • Cardiovascular • Hypertension

First Quarter 2025 and Recent Significant Business Highlights (Businesswire) - "Achieved global net product revenues for AMVUTTRA and ONPATTRO for the first quarter of $310 million and $49 million, respectively, representing 36% growth compared to Q1 2024...Achieved global net product revenues for GIVLAARI and OXLUMO for the first quarter of $67 million and $42 million, respectively, representing 8% growth compared to Q1 2024."

Sales • Amyloidosis • Cardiomyopathy • Genetic Disorders • Renal Disease

CHMP post-authorisation summary of positive opinion for Amvuttra (II-15) (European Medicines Agency) - "On 25 April 2025, the Committee for Medicinal Products for Human Use (CHMP) adopted a positive opinion, recommending a change to the terms of the marketing authorisation for the medicinal product Amvuttra....The CHMP adopted an extension to an existing indication to include treatment of wild-type or hereditary transthyretin amyloidosis in adults with cardiomyopathy.The full indications for Amvuttra will therefore be as follow: Amvuttra is indicated for the treatment of wild-type or hereditary transthyretin amyloidosis in adult patients with cardiomyopathy (ATTR-CM)."

CHMP • Amyloidosis • Cardiomyopathy

Vutrisiran for Transthyretin Amyloidosis Cardiomyopathy. (PubMed, Curr Vasc Pharmacol) - No abstract available

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

More players in the treatment of transthyretin amyloidosis? The HELIOS-B study. (PubMed, Eur Heart J Suppl) - "The mean age was 77 years, and 40% received tafamidis at baseline. Treatment with vutrisiran resulted in a reduction in all-cause and CV mortality events, as well as preservation of functional capacity, quality of life, and health status in patients with TTR cardiomyopathy."

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

Transthyretin as a therapeutic target: the future of disease-modifying therapies for Alzheimer's disease. (PubMed, Mol Biol Rep) - "Recent research has revealed that TTR is gradually showcasing its promise in neuroprotection and neuronal viability in AD by binding with Aβ and mitigating its neurotoxic effects. Current preclinical and clinical studies also support that TTR is actively involved in maintaining the blood-brain barrier (BBB) integrity and maintain neurotransmitter balance, all of which offer significant therapeutic promise through TTR stabilizers, such as Tafamidis, Acoramidis, and Vutrisiran, highlighting their potential in AD treatment This review concludes that TTR plays bidirectional role and gaining interest as a potential biomarker, though several challenges must be addressed before it can be established a novel therapeutic target in AD management in the modern era of drug discovery."

Biomarker • Journal • Review • Alzheimer's Disease • CNS Disorders

4017 - Introduction to AMVUTTRA® (vutrisiran) (ACC 2025) - "Industry-Expert Theater presentations are not part of ACC.25, as planned by its Program Committee, and do not qualify for continuing medical education (CME), continuing nursing education (CNE) or continuing education (CE) credit. Sponsored by Alnylam Pharmaceuticals"

IMPROVEMENT IN MEASURES OF QUALITY OF LIFE AMONG PATIENTS RECEIVING TARGETTED THERAPY FOR ATTR AMYLOIDOSIS: A META-ANALYSIS OF DATA FROM RANDOMIZED CONTROLLED TRIALS - Shubhashis Saha (ACC 2025) - "Background: Novel drugs like patisiran, vutrisiran, tafamidis, acoramidis, eplontersen, and inotersen reduce the synthesis and deposition of TTR amyloid fibrils in patients with cardiac amyloidosis. Contemporary drugs for cardiac amyloidosis improved quality of life and 6MWT, while having a good safety profile. Although they are usually classified as secondary outcomes in many clinical trials, these improvements would be more relevant to the patients in short to medium term."

HEOR • Retrospective data • Amyloidosis • Cardiac Amyloidosis • Cardiovascular

LACK OF IMPROVEMENT IN CARDIAC FUNCTION AMONG PATIENTS RECEIVING TARGETTED THERAPY FOR ATTR AMYLOIDOSIS: A META-ANALYSIS OF DATA FROM RANDOMIZED CONTROLLED TRIALS - Revati Varma (ACC 2025) - "Background: Novel drugs like patisiran, vutrisiran, tafamidis, acoramidis, eplontersen, and inotersen reduce the synthesis and deposition of TTR amyloid fibrils in patients with cardiac amyloidosis (CA). Contemporary drugs for CA did not result in changes in the cardiac structure on echocardiographic parameters while having a good safety profile."

Retrospective data • Amyloidosis • Cardiac Amyloidosis • Cardiovascular

A RARE, UNUSUALLY AGGRESSIVE FORM OF HEREDITARY TRANSTHYRETIN AMYLOIDOSIS WITH SUBSTANTIAL SYSTEMIC, NEUROLOGIC, AND LEPTOMENINGEAL AMYLOID INFILTRATION IN A YOUNG PATIENT - Jingwen Zhang (ACC 2025) - "Vutrisiran was initiated for ATTRv. Efforts to obtain access to tafamidis are also underway, as it crosses the blood-brain barrier and may treat leptomeningeal amyloidosis. Leptomeningeal amyloidosis is an extremely rare, relentlessly progressive manifestation of ATTRv that may include infiltration into other organs, e.g. the heart and GI tract. Leptomeningeal amyloidosis is an extremely rare, relentlessly progressive manifestation of ATTRv that may include infiltration into other organs, e.g. the heart and GI tract. This case highlights the phenotypic variability of ATTRv and the importance of genetic testing. Knowledge of the phenotypic manifestations of the TTR genotype can influence the workup and treatment of ATTRv."

Clinical • Amyloidosis • Anorexia • Cardiac Amyloidosis • CNS Disorders • Congestive Heart Failure • Gastrointestinal Disorder • Heart Failure • Pain

NANOTECHNOLOGY TO TREAT TRANSTHYRETIN MEDIATED CARDIAC AMYLOIDOSIS - Arafat Farooqui (ACC 2025) - "Random effects model was employed when there was significant heterogeneity (>40%, as assessed by I-squared). Four RCTs were finalized (n=1556; RNAi: 819, placebo: 737) that studied Patisiran (371) and Vutrisiran (448). Pooled analysis showed that RNAi molecules improved the echocardiographic parameters of study population with decrease in cardiac biomarkers and improvement in overall mortality in TTR-mediated cardiac amyloidosis."

Amyloidosis • Cardiac Amyloidosis • Cardiovascular

CARDIOVASCULAR OUTCOMES OF TARGETED THERAPIES FOR TRANSTHYRETIN-ASSOCIATED AMYLOID CARDIOMYOPATHY - Sammudeen Ibrahim (ACC 2025) - "Our study highlights the efficacy of tafamidis, vutrisiran, acoramidis, and diflunisal in significantly improving all-cause mortality, OHT, and CV hospitalizations in patients with ATTR-CM. Conversely, patisiran did not demonstrate significant benefits on the evaluated outcomes."

Amyloidosis • Cardiac Amyloidosis • Cardiomyopathy • Cardiovascular

TRIUMPH OVER AMYLOIDOSIS: A CASE OF SUCCESSFUL DUAL ORGAN TRANSPLANT IN A PATIENT WITH ATTR AND SMOLDERING MYELOMA THROUGH MULTIDISCIPLINARY CARE - Vasili Katsadouros (ACC 2025) - "This case demonstrates the importance of a multi-disciplinary team in transplant management of complex patients with amyloidosis. With early and effective interventions, patients will have improved outcomes."

Clinical • Amyloidosis • Cardiovascular • Chronic Kidney Disease • Congestive Heart Failure • Heart Failure • Hematological Malignancies • Multiple Myeloma • Musculoskeletal Pain • Nephrology • Oncology • Renal Disease • Smoldering Multiple Myeloma • Solid Organ Transplantation • Transplantation

GEOGRAPHIC DISPARITIES IN CARDIAC AMYLOIDOSIS PRESCRIBING PATTERNS: INSIGHTS FROM EPIC COSMOS - Mirza S. Khan (ACC 2025) - "Medications included novel amyloid therapies tafamidis, vutrisiran, patisiran, eplontersen, inotersen and diflunisal. The highest prescription rates for cardiac amyloidosis therapies were in the Northeast U.S., known to have a high density of dedicated amyloidosis centers. Our findings underscore the need for efforts to improve recognition and diagnosis of cardiac amyloidosis and improve treatment access in underserved regions."

Amyloidosis • Cardiac Amyloidosis • Cardiovascular • Congestive Heart Failure • Heart Failure

MAINTENANCE OR IMPROVEMENT OF FUNCTIONAL CAPACITY, HEALTH STATUS, AND QUALITY OF LIFE WITH VUTRISIRAN IN PATIENTS WITH TRANSTHYRETIN AMYLOIDOSIS WITH CARDIOMYOPATHY: DATA FROM THE HELIOS-B STUDY - Farooq H. Sheikh (ACC 2025) - "Significantly more patients treated with vutrisiran maintained or improved functional capacity and health status/QOL compared with placebo, providing further evidence of the disease-modifying effect of vutrisiran treatment."

Clinical • HEOR • Amyloidosis • Cardiac Amyloidosis • Cardiomyopathy • Cardiovascular

IMPACT OF BASELINE HEART FAILURE SEVERITY ON EFFICACY OF VUTRISIRAN IN PATIENTS WITH TRANSTHYRETIN AMYLOIDOSIS WITH CARDIOMYOPATHY IN THE HELIOS-B TRIAL: A SUBGROUP ANALYSIS - Mathew S. Maurer (ACC 2025) - P3 | "In patients with ATTR-CM, the benefits of vutrisiran vs placebo on ACM, CV events, functional capacity, health status and QoL, and cardiac biomarkers were consistent across different baseline heart failure severity groups defined by NYHA Class or NT-proBNP level."

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

THE RELATIONSHIP BETWEEN CARDIAC STRUCTURE, FUNCTION, AND CLINICAL OUTCOMES, AND THE IMPACT OF VUTRISIRAN FROM THE HELIOS-B TRIAL - Karola Jering (ACC 2025) - "The primary endpoint was a composite of ACM and recurrent CV events (CV hospitalizations and urgent heart failure visits) assessed separately in the overall population and in the monotherapy population (defined as patients not on tafamidis at baseline). Improvements in cardiac structure and function support the benefits of vutrisiran in reducing the risk of CV events and ACM compared to placebo for patients with ATTR-CM."

Clinical • Clinical data • Cardiomyopathy • Congestive Heart Failure • Heart Failure