Onpattro (patisiran) / Alnylam, Arbutus, Sanofi, Medison - LARVOL DELTA

Class-Specific Adverse Events of Patients Treated with Small Interfering RNA Therapeutics: A Disproportionality Analysis of the United States Food and Drug Administration Adverse Event Reporting System Database Based on the MY FAERS Platform. (PubMed, Nucleic Acid Ther) - "This study aimed to identify and quantify CAE-siRNA associated with U.S. Food and Drug Administration (FDA)-approved siRNA drugs (patisiran, givosiran, vutrisiran, inclisiran, and lumasiran) using real-world pharmacovigilance data, focusing on potential class-wide effects. This study identified clinically relevant CAE-siRNA, particularly hepatic toxicity for inclisiran, supporting enhanced monitoring. While disproportionality analyses are hypothesis generating, these findings underscore the need for targeted pharmacovigilance to optimize the safety of this promising drug class."

Adverse events • Journal • Back Pain • Fatigue • Gastroenterology • Gastrointestinal Disorder • Musculoskeletal Pain • Pain

Emerging nanotechnology-enabled siRNA oral delivery platforms. (PubMed, Nanomedicine (Lond)) - "Nanotechnology-based platforms have enabled delivery of siRNA and have already been clinically validated for intravenous (IV) infusion administration (e.g patisiran)...Together, these advances outline a promising path toward clinically viable, patient-friendly siRNA therapeutics delivered orally. Literature for this review was identified through database searches [University of New Mexico University Libraries, Web of Science, Google Scholar, and PubMed databases April 2025-November 2025] as it related to the oral delivery of nanoparticles, siRNA-loaded nanoparticles, gene therapy, and related nanomedicine delivery strategies."

Journal • Review • Gastrointestinal Disorder • Gene Therapies

Role SGLT2 inhibitor therapy in patients with transthyretin cardiac amyloidosis: a GRADE assessed systematic review and meta-analysis. (PubMed, Acta Cardiol) - "Transthyretin amyloid cardiomyopathy (ATTR-CM) patients continue to experience worsening heart failure despite therapy with disease modifying therapies (tafamidis, patisiran, etc.). However, these findings are derived from observational studies with their inherent biases and must be interpreted with caution. High-quality randomised controlled trials are needed to confirm these associations and better define their clinical role in ATTR-CM."

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

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

Trial completion • Amyloidosis • Cardiac Amyloidosis

Relative efficacy of tafamidis, acoramidis, patisiran and vutrisiran in patients with transthyretin cardiac amyloidosis: a network meta-analysis. (PubMed, Eur Heart J Open) - "When the ATTR-ACT trial was excluded from the analysis, vutrisiran monotherapy consistently showed the highest probability of being ranked better than other treatments in terms of primary end-point. Although differences in trial design and study populations complicate direct efficacy comparisons, tafamidis demonstrated the highest efficacy in improving survival, reducing cardiovascular hospitalizations, and enhancing functional capacity and quality of life in patients with ATTR-CA, but also vutrisiran and acoramidis emerged as viable options."

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

Real-world effectiveness of targeted therapies in ATTR cardiomyopathy: A meta-analysis integrating population-based data. (PubMed, ESC Heart Fail) - "Targeted treatments for ATTR-CM significantly reduce mortality and cardiovascular hospitalizations. When extrapolated to population-level data, these treatments show clinical benefits, emphasizing the importance of early diagnosis and therapeutic intervention."

Journal • Real-world evidence • Retrospective data • Amyloidosis • Cardiac Amyloidosis • Cardiomyopathy • Cardiovascular

Dually Decorated Palmitate-Containing Lipid Nanoparticles for the Targeted Delivery of siRNAs against HER2 and Hsp27 in HER2+ Breast Cancer. (PubMed, J Med Chem) - "Ionizable lipid nanoparticles (LNPs) have enabled significant advances in oligonucleotide (ON) therapeutics, resulting in the approval of the short interfering RNA (siRNA)-based formulation Onpattro...By altering the targeting peptide and siRNA combination, it could be adapted for diverse tumors and combination treatments. Additionally, palmitic acid inclusion further enhanced cytotoxicity in palmitate-sensitive cells, offering additional therapeutic advantages."

Journal • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Oncology • Solid Tumor • HER-2 • SSTR • SSTR2

Lipid Nanoparticle Library Screen Reveals Lymphatic Endothelial Cell-Targeting Lipid Nanoparticle for Delivering Vascular Endothelial Growth Factor C mRNA after Lymphatic Injury. (PubMed, ACS Nano) - "We identified and validated several LNP formulations optimized for high LEC uptake when administered ID and compared their efficacy for delivery of functional mRNA with that of free mRNA and mRNA delivered with a commercially available MC3-based LNP (Onpattro)...A single dose of VEGFC mRNA delivered via LNP7 resulted in enhanced LEC proliferation at the site of injury and an increase in lymphatic function up to 14 days postsurgery. Our results suggest a therapeutic potential of VEGFC mRNA using lymphatic-enriched LNP delivery for alleviating lymphatic dysfunction observed during lymphatic injury and could provide a promising approach for targeted and transient lymphangiogenic therapy."

Journal • Oncology • Palliative care • VEGFA • VEGFC

Lipid Nanoparticle Library Towards Development of Next Generation Genomic Medicines (ASH 2023) - "Ionizable amino lipids are a major constituent of the lipid nanoparticles for delivering nucleic acid therapeutics (e. g. , DLin-MC3-DMA in ONPATTRO®, ALC-0315 in Comirnaty®, SM-102 in Spikevax®). Further, using ionizable lipids from the library, we have shown gene editing of various targets in rodents. We believe that these studies will pave the path to the advancement in nucleic acid based therapeutics and vaccines, or cell & gene therapy agents for early diagnosis and detection of cancer, and for targeted genomic medicines towards cancer treatment and diagnosis."

Lipid Nanoparticle • Gene Therapies

Patterns of Treatment Adherence and Administration Preferences for People With Transthyretin Amyloid Cardiomyopathy: A Real-World Survey in Europe, the United States, and Japan (ISPOR-EU 2025) - "At survey, 73% of patients were prescribed treatment, of which 93% were prescribed DMTs including tafamidis (85%), patisiran (6%), vutrisiran (2%) and diflunisal (2%). Tafamidis was the most frequently prescribed DMT, and adherence was high. Patients more frequently reported feeling comfortable with oral medications than injections/infusions, particularly once daily orals, underscoring the relevance of administration preferences among treatment landscapes. Further research is needed to explore outcomes with ATTR treatments."

Adherence • Clinical • Real-world • Real-world evidence • Amyloidosis • Cardiac 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

Coramitug, a Humanized Monoclonal Antibody for the Treatment of Transthyretin Amyloid Cardiomyopathy: a Phase 2, Randomized, Multicenter, Double-Blind, Placebo-Controlled Trial. (PubMed, Circulation) - "This phase 2 trial showed that coramitug, an antibody targeting misfolded transthyretin in ATTR-CM, was well tolerated and at a dose of 60 mg/kg resulted in a statistically significant reduction in NT-proBNP, a validated marker of disease progression, with no statistically significant effect on 6MWT within 52 weeks."

Journal • P2 data • Amyloidosis • Cardiac Amyloidosis • Cardiomyopathy • Cardiovascular • Congestive Heart Failure • Heart Failure

RNA Interference Therapeutics for Hereditary Transthyretin-Mediated Amyloidosis with Neuropathy: A Systematic Review (ASH 2024) - "Currently, limited treatment options are available for ATTRv, which include orthotopic liver transplantation and transthyretin tetramer stabilizers (tafamidis or diflunisal)...The most common cause of death reported was cardiac failure.Conclusion : RNA interference therapies, including Eplontersen, Inotersen, Vutrisiran, and Patisiran, have demonstrated significant benefits in enhancing the quality of life for patients with ATTRv and associated polyneuropathy...While RNAi therapies offer substantial symptomatic relief, vigilant surveillance for side effects is crucial to optimize patient outcomes and ensure safety. Further studies, including comparative studies, are essential to establish therapeutic protocols and ensure improved quality of life for patients with ATTRv."

Review • Amyloidosis • Cardiac Amyloidosis • Cardiomyopathy • Cardiovascular • CNS Disorders • Congestive Heart Failure • Diabetic Neuropathy • Glomerulonephritis • Heart Failure • Hematological Disorders • Lupus Nephritis • Nephrology • Pain • Renal Disease • Thrombocytopenia

Neurological efficacy and safety of RNA therapeutics in hereditary transthyretin amyloidosis: a systematic review and meta-analysis of randomized controlled trials. (PubMed, Ther Adv Cardiovasc Dis) - "RNA therapeutics are effective and well-tolerated in patients with hATTR, significantly improving quality of life and the progression of neurological impairment. siRNAs demonstrate better outcomes compared to ASOs."

Journal • Retrospective data • Review • Amyloidosis • Cardiac Amyloidosis • Diabetic Neuropathy • Gastrointestinal Disorder • Pain

Optimization of Targeted Lipid Nanoparticle for the Treatment of RUNX1::ETO Driven AML (ASH 2024) - "To address these challenges, we began by modifying the lipid composition of a Standard LNP based on the marketed Onpattro formulation, incorporating a tripeptide, LDV (Leu-Asp-Val), to target the Very Late Antigen-4 (VLA-4) receptor present on all hematopoietic cells (Swart et al, 2023)...These advancements are especially significant for treating fusion gene-driven leukemias, offering the potential for more effective RNA-based therapies with enhanced targeting and reduced side effects. This is an encouraging step forward in improving outcomes for leukemia patients."

Lipid Nanoparticle • Acute Myelogenous Leukemia • Hematological Malignancies • Infectious Disease • Infertility • Leukemia • Oncology • Pediatrics • Sexual Disorders • RUNX1

The Nanoparticle-Mediated Delivery of Therapeutic Sirnas Targeting the KMT2A::Afdn Fusion Gene in AML (ASH 2024) - "First, we assessed the delivery and knockdown efficiency using the Onpattro (Patisiran) LNP formulation, which consists of DLin-MC3-DMA, DSPC, cholesterol and DMG-PEG2000 at the molar ratios 50 : 10 : 38.5 : 1.5, respectively...Furthermore, the colony formation was decreased following KMT2A : : AFDN knockdown, which is in line with the loss of SHARP1. As such, the knockdown of KMT2A : : AFDN with LNPs shows great potential in the treatment of t(6; 11) AML."

Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology • Pediatrics • AFDN • DOT1L • KIT • KMT2A

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

Gastrointestinal Amyloidosis: Unmasking the Hidden Culprit of Chronic Epigastric Pain and Weight Loss (ACG 2025) - "Recent trials support daratumumab for AL and patisiran/inotersen for ATTR amyloidosis. Early, accurate diagnosis is key to initiating appropriate therapy and improving outcomes, with multidisciplinary involvement crucial for optimal care."

Amyloidosis • Cardiovascular • Constipation • Gastroenterology • Gastroesophageal Reflux Disease • Gastrointestinal Disorder • Heart Failure • Hematological Malignancies • Hepatitis B • Hepatology • Infectious Disease • Lymphoma • Monoclonal Gammopathy • Pain • Renal Disease

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

Unlocking the potential of nanoparticle extrahepatic delivery using high-throughput screening to enable expanded machine learning design of novel chemistry (ESGCT 2024) - "With the approval of ONPATTRO and COVID mRNA vaccines, most development is limited to liver indications and vaccines...We have further expanded upon that approach by integrating peptide barcoding into our screening funnel allowing us to rapid screen for biodistribution of mRNA in organs and tissues of interest and then identify those LNPs which also demonstrate productive delivery through robust peptide sequencing. This platform results in much cheaper and quicker screening of LNPs."

Machine learning • Novel Coronavirus Disease

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

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

Influence of polyethylene glycol on the mucus penetration and stability of lipid nanoparticles in cryopreservation and lyophilization. (PubMed, RSC Adv) - "Lipid nanoparticles (LNPs) have emerged as clinically validated drug delivery vehicles, as demonstrated by the successful deployment of COVID-19 mRNA vaccines (Comirnaty and Spikevax) and siRNA therpy (Patisiran). Stability assessments showed that LNPs remained stable in PEG media at -20 °C for 4 weeks. However, none of the tested PEG formulations prevented LNPs aggregation during lyophilization."

Journal • Infectious Disease • Novel Coronavirus Disease

Revolutionizing pediatric gene and cell therapy: The hope for lipid-based nanoparticles in blood disorders. (PubMed, Curr Res Transl Med) - "In 2018, the first FDA-approved LNP-based siRNA therapy (Patisiran/ Onpattro®) for treating hereditary amyloidosis brought attention to the feasibility of LNPs for gene therapy. Eventually, authorization and approval of the mRNA-LNP vaccines against COVID-19 (Comirnaty® of BioNTech/Pfizer and SpikeVax® of Moderna) was another milestone for the development of LNP-based nucleic acid therapies...This innovative approach offers a brighter future for pediatric healthcare, where children can look forward to healthier and more fulfilling lives. This review paper provides an overview of the applications of LNPs in gene and cell therapies with a special focus on their pre-clinical application in primary cells, including natural killer cells, T cells, and hematopoietic stem cells, highlighting LNPs' efficacy, safety profile, and potential for transforming the landscape of pediatric healthcare in the future."

Journal • Review • Amyloidosis • Gene Therapies • Genetic Disorders • Hematological Disorders • Infectious Disease • Novel Coronavirus Disease • Oncology • Pediatrics

Reply to the Letter to the Editor: "Underlying Mechanism of Hypothyroidism in a Patient with ATTRv Receiving Patisiran". (PubMed, Intern Med) - No abstract available

Journal • Amyloidosis • Endocrine Disorders