Amvuttra (vutrisiran) / Alnylam, Sanofi - LARVOL DELTA

Alnylam Presents New Data from the HELIOS-B Phase 3 Study of Vutrisiran in Patients with ATTR Amyloidosis with Cardiomyopathy (ATTR-CM) at the American College of Cardiology’s Annual Scientific Session 2025 (Businesswire) - P3 | N=655 | HEALIOS-B (NCT04153149) | Sponsor: Alnylam Pharmaceuticals | "New echocardiographic data from the HELIOS-B Phase 3 clinical trial...demonstrated that treatment with vutrisiran improved echocardiographic cardiac function. Vutrisiran treatment led to significant improvements in diastolic function and attenuation of declines in left ventricular (LV) and right ventricular (RV) systolic function at Month 18, compared to placebo...An exploratory subgroup analysis demonstrated that vutrisiran reduced all-cause mortality and recurrent cardiovascular events across a range of baseline heart failure severities in patients with ATTR-CM. The greatest benefit was observed in patients with earlier, less severe disease, underscoring the need for timely diagnosis and early intervention....A separate analysis confirmed that vutrisiran significantly maintained or improved functional capacity, and patient-reported health status and quality of life, compared to placebo over 30 months."

P3 data • Amyloidosis • Cardiomyopathy

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

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

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

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

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

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

Precision medicine in the diagnostics and treatment of cardiomyopathies : State of the art (PubMed, Herz) - "Mavacamten treats left ventricular outflow tract (LVOT) obstruction in hypertrophic CMP, while tafamidis and RNA-based treatment, such as patisiran and vutrisiran specifically affect transthyretin-mediated amyloidosis. Artificial intelligence (AI) is pivotal in precision medicine where AI-assisted analyses enhance the diagnosis of subclinical diseases, optimize imaging modalities and accelerate the development of new treatment approaches. The ESC guidelines are an important milestone in the care of patients with CMP, while also emphasizing the need for further research and scientific ethical discussions, especially with respect to AI and innovative forms of treatment."

Journal • Review • Amyloidosis • Cardiomyopathy • Cardiovascular • Gene Therapies

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 Heart Failure Severity on Vutrisiran Efficacy in Transthyretin Amyloidosis with Cardiomyopathy. (PubMed, J Am Coll Cardiol) - P3 | "Vutrisiran demonstrated evidence of benefit across the range of baseline disease severities in HELIOS-B, with the greatest benefit in earlier, less severe disease."

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

Impact of Vutrisiran on Functional Capacity and Quality of Life in Transthyretin Amyloidosis With Cardiomyopathy. (PubMed, J Am Coll Cardiol) - "Vutrisiran maintained or improved functional capacity, health status, and QOL in more patients with ATTR-CM versus placebo over 30 months."

HEOR • Journal • 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

Alnylam Announces FDA Approval of AMVUTTRA (vutrisiran), the First RNAi Therapeutic to Reduce Cardiovascular Death, Hospitalizations and Urgent Heart Failure Visits in Adults with ATTR Amyloidosis with Cardiomyopathy (ATTR-CM) (Businesswire) - "Alnylam Pharmaceuticals...announced the U.S. Food and Drug Administration (FDA) approval of the supplemental New Drug Application (sNDA) for its RNAi therapeutic, AMVUTTRA (vutrisiran), for the treatment of the cardiomyopathy of wild-type or hereditary transthyretin-mediated amyloidosis (ATTR-CM) in adults to reduce cardiovascular mortality, cardiovascular hospitalizations and urgent heart failure visits. The approval expands the indication for AMVUTTRA, which now becomes the first and only therapeutic approved by the FDA for the treatment of ATTR-CM and the polyneuropathy of hereditary transthyretin-mediated amyloidosis (hATTR-PN) in adults....This approval is based on the HELIOS-B Phase 3 clinical trial which evaluated AMVUTTRA for the treatment of ATTR-CM....Alnylam remains on track to proceed with additional global regulatory submissions for vutrisiran in 2025."

FDA approval • Filing • Amyloidosis • Cardiac Amyloidosis • Cardiomyopathy

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

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

Vutrisiran in patients with transthyretin amyloidosis with cardiomyopathy in HELIOS-B who had progressed on tafamidis (HEART FAILURE 2025) - No abstract available

Clinical • Cardiac Amyloidosis • Cardiomyopathy • Cardiovascular

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

Retrospective data • Cardiac Amyloidosis • Cardiovascular

RNAi Therapeutics for hATTR Amyloidosis: A Comprehensive Single Arm Meta-Analysis of Clinical Outcomes and Treatment Efficacy (AAN 2025) - "Objective:The primary objective of this single-arm meta-analysis is to comprehensively evaluate the efficacy and clinical outcomes of RNA interference (RNAi) therapies, specifically patisiran and vutrisiran, in the treatment of hereditary transthyretin amyloidosis (hATTR) with neurologic involvement.Background:New RNA interference (RNAi) therapies, particularly patisiran and vutrisiran, represent a groundbreaking approach in the management of Hereditary Transthyretin Amyloidosis (hATTR). This meta-analysis demonstrates that RNA interference drugs significantly slow progression of disease, substantially improves neurologic symptoms and quality of life, with a favorable safety profile. These findings support its use as a valuable treatment option for hereditary transthyretin amyloidosis. Further research is needed to assess long-term outcomes and comparative effectiveness."

Clinical data • Retrospective data • Amyloidosis • Cardiac Amyloidosis • Pain

Efficacy of Pharmacological Interventions for Transthyretin Familial Amyloid Polyneuropathy (TTR-FAP): A Systematic Review and Network Meta-Analysis (AAN 2025) - "Patisiran and Inotersen demonstrated superior efficacy with significant results, while Vutrisiran and Diflunisal also showed notable outcomes. In contrast, Tafamidis did not yield significant results. Further research is needed to confirm these findings."

Retrospective data • Review • Amyloidosis • CNS Disorders • Diabetic Neuropathy • Pain

Hereditary transthyretin amyloidosis incidentally diagnosed by video-associated lung surgery for lung cancer: A case report. (PubMed, Respir Med Case Rep) - "Finally, treatment with vutrisiran, a small interfering RNA (siRNA) targeting the TTR gene, was successfully initiated. Physicians need to be aware that unidentified amyloidosis may be diagnosed incidentally from a biopsied or resected specimen for another purpose. Diagnosing systemic amyloidosis that may otherwise be overlooked would enable patients to receive benefits from the definitive therapy."

Journal • Video • Amyloidosis • Cardiac Amyloidosis • CNS Disorders • Lung Cancer • Musculoskeletal Pain • Obstructive Sleep Apnea • Oncology • Pain • Respiratory Diseases • Sleep Disorder • Solid Tumor

Therapeutic effect of TTR siRNA on hereditary transthyretin amyloidosis (ATTRv) nephropathy. (PubMed, Amyloid) - "Notably, longitudinal data showed that TTR siRNA therapeutics reduced proteinuria and increased serum protein, while none of the new treatments could demonstrate a significant improvement in the slope of eGFR decline. We demonstrated that TTR siRNA therapeutics represent potential candidates for ATTRv nephropathy, despite the fact that their use has been limited to neurological symptoms to date."

Journal • Amyloidosis • Cardiac Amyloidosis • Renal Disease

Phenotype variability and therapeutic response to Patisiran in patients with hereditary transthyretin amyloidosis: a Belgian real-world experience. (PubMed, Acta Clin Belg) - "Currently, several disease-modifying treatments for hATTRv are available in Belgium including the TTR stabilizer tafamidis and TTR mRNA silencers patisiran and vutrisiran. The cases also highlight the importance of red flags recognition to allow early diagnosis and treatment to prevent further disease progression. Due to the multisystemic nature of the disease and its heterogeneous clinical presentation, close collaboration between neurologists and cardiologists is highly recommended, ideally within a multidisciplinary amyloidosis team, to provide holistic care in hATTRv patients."

Journal • Real-world evidence • Amyloidosis • Cardiac Amyloidosis • Cardiomyopathy • Cardiovascular • Gastrointestinal Disorder • Pain

Alnylam Announces Preliminary Fourth Quarter and Full Year 2024 Global Net Product Revenues and Provides 2025 Combined Net Product Revenue Guidance and Pipeline Goals (Businesswire) - "Vutrisiran...Secure additional global approvals and reimbursement in Japan and the EU for the treatment of adults with ATTR amyloidosis with cardiomyopathy in the second half of 2025. Nucresiran (ALN-TTRsc04) – an investigational RNAi therapeutic in development for the treatment of ATTR amyloidosis. Alnylam expects to: Initiate a Phase 3 study in patients with ATTR amyloidosis with cardiomyopathy in the first half of 2025...Mivelsiran – an investigational RNAi therapeutic in development for the treatment of Alzheimer’s disease and cerebral amyloid angiopathy (CAA). Alnylam expects to: Report interim results from Part B of the Phase 1 study in Alzheimer’s disease in the second half of 2025. Initiate a Phase 2 study in Alzheimer’s disease in the second half of 2025...In 2025, Vir expects to initiate a Phase 3 chronic hepatitis delta registrational study and to report functional cure results from a Phase 2 chronic hepatitis B study."

Approval • New P2 trial • New P3 trial • P1 data • P2 data • Reimbursement • Alzheimer's Disease • Amyloidosis • CNS Disorders

Patisiran in ATTRv amyloidosis with polyneuropathy: "PatisiranItaly" multicenter observational study. (PubMed, J Neurol) - "Patisiran can be considered a valid therapeutic option for the management of patients with ATTRv amyloidosis. Considering its mechanism of action, similar outcomes could also be expected with the wider utilization of newly approved gene silencers for ATTRv therapy, such as vutrisiran."

Journal • Observational data • Amyloidosis • Cardiac Amyloidosis • CNS Disorders • Diabetic Neuropathy • Pain

Alnylam Pharmaceuticals Reports Fourth Quarter and Full Year 2024 Financial Results and Highlights Recent Period Progress (Businesswire) - "Achieved global net product revenues for ONPATTRO and AMVUTTRA for the fourth quarter of $56 million and $287 million, respectively, and $343 million combined, representing 35% total TTR growth compared to Q4 2023, and full year 2024 revenues of $253 million and $970 million, respectively, and $1,223 million combined, representing 34% total TTR growth compared to full year 2023...Achieved global net product revenues for GIVLAARI and OXLUMO for the fourth quarter of $65 million and $44 million, respectively, and $108 million combined, representing 18% total Rare growth compared to Q4 2023, and full year 2024 revenues of $256 million and $167 million, respectively, and $423 million combined, representing 29% total Rare growth compared to full year 2023."

Commercial • Amyloidosis • Genetic Disorders • Rare Diseases • Renal Calculi • Renal Disease