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

Hereditary Transthyretin Amyloidosis (ATTRv): finerenone along the spectrum of kidney and heart disease (ERA 2025) - "Anti-amyloid therapy included liver transplantation (n=13; 61.90%), tafamidis (n=5; 23.81%), and patisiran (n=3; 14.29%). In ATTRv, finerenone has shown efficacy in kidney protection, including in the setting of heart failure with preserved ejection fraction (HFpEF). It significantly reduces proteinuria (PCR) while demonstrating good tolerability, avoiding the deleterious hypotension associated with dysautonomia and minimizing complications related to neurogenic bladder. Furthermore, its use does not lead to significant changes in potassium levels."

Acute Kidney Injury • Amyloidosis • Cardiac Amyloidosis • Cardiomyopathy • Cardiovascular • Chronic Kidney Disease • Congestive Heart Failure • Diabetes • Diabetic Nephropathy • Fabry Disease • Genetic Disorders • Heart Failure • Hypotension • Infectious Disease • Nephrology • Renal Disease

Endosomal disruption by co-encapsulating gentamicin in lipid nanoparticles for efficient siRNA delivery and cancer therapy. (PubMed, Asian J Pharm Sci) - "We encapsulated gentamicin(GM) into the marketed Onpattro® formulation to establish LNP-siRNA/GM nanoparticles that promote siRNA endo-lysosomal escape through endosomal disruption, mechanistically exhibiting unique functionality and synergistic effects of LNP-siRNA/GM to improve cancer therapy. The combination of EGFR-siRNA and GM could also greatly inhibit angiogenesis, be antiproliferative, and induce tumor cells apoptosis. Therefore, this GM and siRNA co-delivery system would provide an efficient strategy for siRNA endosomal escape, significantly improving knockdown in various LNPs based siRNA delivery systems and efficiently enhancing cancer therapy."

Journal • Oncology • CXCL12 • EGFR

REGRESSION OF AMYLOID LOAD IN SUBCUTANEOUS FAT TISSUE OF HEREDITARY TRANSTHYRETIN AMYLOIDOSIS PATIENTS DURING TREATMENT WITH PATISIRAN (EULAR 2025) - "This study is the first to provide evidence of regression of amyloid in tissue of ATTRv amyloidosis patients who are treated with gene-silencing therapy. Congo red score decreases after a median of 36 months, but differences on group levels can already be detected 2 years after initiation of patisiran. The level of serum transthyretin reduction does not correlate with the decrease in Congo red score in fat tissue in our population, however, analysis of predictors of amyloid regression are ongoing."

Clinical • Amyloidosis • Cardiac Amyloidosis • Pain

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

A novel lipopolyplex platform for dual mRNA delivery via core- and surface-loading. (PubMed, J Control Release) - "The approval of Onpattro® (2018) and Comirnaty (2020) has driven interest in nanoparticulate nucleotide delivery. Additionally, the role of mRNA localization within the LPP was investigated. Surface-loaded mRNA demonstrated superior transfection efficiency and shear resistance compared to core-loaded mRNA, which lost functionality under nebulization."

IO biomarker • Journal • Gene Therapies • Oncology

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

Evolving disease characteristics in cardiac amyloidosis: real-world data from a tertiary referral center (HEART FAILURE 2025) - "Overall mortality was lower when receiving disease-modifying therapy (DMT, tafamidis/patisiran), which is prescribed in NYHA class ≤II (p<0.001). Medical and device therapy also significantly changed. These changes have implications for prognostication and on-going research."

Clinical • Real-world • Real-world evidence • 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 (ESC-WCC 2025) - No abstract available

Retrospective data • Cardiac Amyloidosis • Cardiovascular

Rational Design and Preclinical Applications of Long Circulating Lipid Nanoparticles (lcLNPs) for Extra Hepatic Delivery of Nucleic Acids (ASGCT 2025) - "Lipid nanoparticles have already enabled successful delivery and manipulation of targets in the liver as demonstrated by the first ever approved RNAi therapeutic, Onpattro...This further supports the hypothesis that extrahepatic delivery can be achieved by extending circulation profiles of LNPs. Disease Focus of Abstract:Other Other: Delivery"

Lipid Nanoparticle • Preclinical • Gene Therapies

Delivery, Potency and Tolerability of Lipid Nanoparticle Formulations of mRNA in PXB-Mice (ASGCT 2025) - "Lipid nanoparticles (LNP) enable effective delivery of RNA-based therapeutics and have been clinically validated in approved intravenous products, including ONPATTRO®...Despite this, PXB-mice (and other liver-humanized mice) represent a promising preclinical model for mRNA-LNP testing and may be particularly useful in characterizing the biology of human-specific payloads when using highly active LNP. Disease Focus of Abstract:Liver Diseases"

Lipid Nanoparticle • Preclinical • Dyslipidemia • Hepatology • APOE

Mobilize LNPs: A Novel Platform for In Vivo Targeted Delivery of RNA Therapeutics to T Cells (ASGCT 2025) - "Introduction: Lipid nanoparticles (LNPs) have cemented their utility as efficient and effective delivery systems for RNA-based therapeutics with successful clinical translation as COVID vaccines (CORMIRNATY® and Spikevax) and hepatic delivery (ONPATTRO®). The Mobilize platform consistently demonstrates the ability to both (1) detarget the liver, (thus avoiding passive LNP sinks), and (2) specifically deliver to T-cells in vitro and in vivo in multiple models. The inherent design of the Mobilize platform elegantly addresses the challenges in functionalizing LNPs with targeting ligands for extra-hepatic delivery. The process behind Mobilize technology maintains platform versatility, stability, robustness, and delivery efficiency."

Preclinical • Novel Coronavirus Disease

Rational Design and Preclinical Applications of Novel Unshielded Lipid Nanoparticles (uLNPs) (ASGCT 2025) - "Onpattro, the first-ever approved RNAi therapeutic, is an siRNA-LNP against transthyretin and is indicated for the treatment of hereditary transthyretin amyloidosis...These novel 3-component uLNPs show excellent physicochemical properties and long-term stability making them an exciting platform to explore for range of other therapeutic applications. Disease Focus of Abstract:Other Other: Delivery"

Lipid Nanoparticle • Preclinical • Amyloidosis • Cardiac Amyloidosis • Gene Therapies • Immunology • APOE • CD4 • CD8

Liposomal lipid nanoparticles for extrahepatic delivery of mRNA (Pre-Recorded Presentation) (ASGCT 2025) - "These liposomal LNPs exhibit longer circulation lifetimes than LNP systems with Onpattro-like lipid compositions and have enhanced extrahepatic transfection properties. The prolonged blood circulation lifetime is attributed to reduced plasma protein adsorption. The transfection competency of liposomal LNP systems is attributed to export of the solid core containing mRNA from the LNP as the endosomal pH is lowered."

Reduction in amyloid deposition after patisiran in ATTRv patients: Assessment by biopsy, PET, and PYP scintigraphy (JSNE 2025) - No abstract available

Biopsy • Clinical • Gene Therapies • Pain

Liposomal lipid nanoparticles for extrahepatic delivery of mRNA. (PubMed, Nat Commun) - "These liposomal LNPs exhibit longer circulation lifetimes than LNP systems with Onpattro-like lipid compositions and have enhanced extrahepatic transfection properties. The prolonged blood circulation lifetime is attributed to reduced plasma protein adsorption. The transfection competency of liposomal LNP systems is attributed to export of the solid core containing mRNA from the LNP as the endosomal pH is lowered."

Journal

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

Patisiran Treatment in the Brazilian Subpopulation of the Phase 3 APOLLO-B Study in Transthyretin Amyloidosis with Cardiomyopathy: Post Hoc Analysis. (PubMed, Arq Bras Cardiol) - P3 | "Perugini grade improved in 11/18 (61.1%) and 0/10 evaluable patients with patisiran and placebo, respectively. There were no deaths in the patisiran group vs. 3 in the placebo group."

Biomarker • Clinical • Journal • P3 data • Retrospective data • Amyloidosis • Cardiac Amyloidosis • Cardiomyopathy • Cardiovascular

A scientometric study on research characteristics and trends of amyloidosis involving the oral cavity. (PubMed, J Dent Sci) - "The trend of drug aspect, e.g. prednisone, colchicine, corticosteroid, doxorubicin, and vincristine before 2015 has changed to monoclonal antibody, daratumumab, tafamidis, proteasome inhibitor, carfilzomib, ixazomib, patisiran, pomalidomide, diflunisal, and doxycycline. Herein, we highlight the awareness of early diagnosis and improve the access to care for amyloidosis, since oral involvement frequently constitutes the first sign of this disease. This scientometric study elucidated the current scenario and research trends of amyloidosis, underpinning that stomatologists can play roles in providing early recognition and timely diagnosis of amyloidosis when it involved the oral cavity."

Journal • Amyloidosis • Cardiac Amyloidosis • Cardiomyopathy • Cardiovascular • Hematological Malignancies • Multiple Myeloma • Oncology

Etiological Treatment of Cardiac Amyloidosis: Standard of Care and Future Directions. (PubMed, Curr Heart Fail Rep) - "The standard of care for ATTR-CA include agents capable of selectively stabilizing the precursor protein (e.g., tafamidis), whereas the plasma cell clone is the main target of chemotherapy for AL-CA...Recent data from ATTRibute-CM led to the approval of acoramidis, whereas patisiran received refusal based on the APOLLO-B trial. Novel CRISPR-Cas9-based drugs (i.e., NTLA-2001) hold great potential in the setting of ATTR-CA...However, the investigation of monoclonal antibodies targeting misfolded ATTR (e.g., PRX004, NI301A) or AL (e.g., birtamimab, anselamimab) has led to encouraging results. Various cutting-edge strategies are being tested for treatment of CA and may change the prognostic landscape of this condition in the next years."

Journal • Review • Amyloidosis • Cardiac Amyloidosis • Cardiovascular • Hematological Disorders

The Fomivirsen, Patisiran, and Givosiran Odyssey: How the Success Stories May Pave the Way for Future Clinical Translation of Nucleic Acid Drugs. (PubMed, BioDrugs) - "Givosiran (Givlaari; Alnylam) further revolutionized the field with a carrier-free, targeted platform, utilizing N-Acetylgalactosamine (GalNAc)-siRNA conjugates to enable efficient delivery, expanding therapeutic applications beyond rare genetic disorders to more common conditions such as hyperlipidemia and hypertension. In this review paper, we highlight the evolution of nucleic acid-based drug development, focusing on the pioneering agents fomivirsen, patisiran, and givosiran, and discuss the ongoing challenges in advancing these therapeutics and vaccines."

Journal • Cardiovascular • Dyslipidemia • Genetic Disorders • Hypertension

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

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