vupanorsen (AKCEA-ANGPTL3-LRx) / Ionis, Pfizer 
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  • ||||||||||  vupanorsen (AKCEA-ANGPTL3-LRx) / Ionis, Pfizer
    Preclinical, Journal:  Gene Silencing of Angiopoietin-like 3 (ANGPTL3) Induced De Novo Lipogenesis and Lipid Accumulation in Huh7 Cell Line. (Pubmed Central) -  Apr 17, 2024   
    Vupanorsen, an ANGPTL3 directed antisense oligonucleotide, showed an unexpected increase in liver fat content in humans...The effect of ANGPTL3-siRNA on the expression of genes involved in the de novo lipogenesis was not counteracted by gene silencing of PCSK9. In conclusion, our in vitro study suggests that ANGPTL3 silencing determines lipid accumulation in Huh7 cells by inducing the de novo lipogenesis independently from PCSK9.
  • ||||||||||  Review, Journal:  Advances in Dyslipidaemia Treatments: Focusing on ApoC3 and ANGPTL3 Inhibitors. (Pubmed Central) -  Feb 1, 2024   
    The antisense oligonucleotide (ASO) vupanorsen targeting ANGPTL3 was less effective in reducing LDL-C in patients with moderate hypertriglyceridaemia and its development has been discontinued but the small interfering RNA (siRNA) ARO-ANG3 is being investigated in Phase 2 studies...Olezarsen is an N-acetylgalactosamine-conjugated ASO targeting apoC3 which appears as effective as volanesorsen without the risk of thrombocytopaenia and is undergoing Phase 3 trials. ARO-APOC3 is an siRNA targeting apoC3 that is currently being investigated in Phase 3 studies.
  • ||||||||||  vupanorsen (AKCEA-ANGPTL3-LRx) / Ionis, Pfizer
    Journal:  Hepatic fat changes with antisense oligonucleotide therapy targeting ANGPTL3. (Pubmed Central) -  Jan 2, 2024   
    Increases in HFF were only moderately correlated with elevations in AST and ALT, suggesting that liver enzymes are an imperfect indicator to detect increases in hepatic fat. These results highlight the need to monitor HFF in clinical trials of therapies targeting intracellular ANGPTL3 inhibition, especially those that are targeted to the liver.
  • ||||||||||  vupanorsen (AKCEA-ANGPTL3-LRx) / Ionis, Pfizer
    Journal:  ANGPTL3 Deficiency and Risk of Hepatic Steatosis. (Pubmed Central) -  Nov 8, 2023   
    ANGPTL3 deficiency related to LoF mutations in ANGPTL3, as well as genetically determined reduction of plasma ANGPTL3 levels, is not associated with hepatic steatosis. Therapeutic approaches to inhibit ANGPTL3 production in hepatocytes are not necessarily expected to result in the increased risk for hepatic steatosis that was observed with vupanorsen.
  • ||||||||||  ARO-ANG3 / Arrowhead, vupanorsen (AKCEA-ANGPTL3-LRx) / Ionis, Pfizer
    Journal:  Angiopoietin-like 3 inhibition and the liver: less is more? (Pubmed Central) -  Nov 3, 2023   
    An alternative explanation may relate to off-target effects of vupanorsen, which have a molecule- and/or platform-specific origin. For intrahepatic strategies, highly potent ANGPTL3 inhibition will for now require special attention for liver safety.
  • ||||||||||  Review, Journal:  Updates in Drug Treatment of Severe Hypertriglyceridemia. (Pubmed Central) -  Aug 29, 2023   
    siRNA targeting APOC3 and ANGPTL3, namely ARO-APOC3 and ARO-ANG3, are also promising for the treatment of sHTG. However, the ultimate clinical goal of any sHTG treatment, the decrease in the risk of AP, has not been definitively achieved till now by any pharmacotherapy, either approved or in development.
  • ||||||||||  vupanorsen (AKCEA-ANGPTL3-LRx) / Ionis, Pfizer
    P1 data, P2 data, PK/PD data, Clinical Trial,Phase II, Journal:  A population pharmacokinetic and pharmacokinetic-pharmacodynamic analysis of vupanorsen from phase I and phase II studies. (Pubmed Central) -  Jul 17, 2023   
    The developed population PK/PD model was robust to predict the dose-response relationships. The model predicted that ANGPTL3 target reduction of 75% can be sufficiently achieved with a 320-mg monthly dose of vupanorsen, but target values for TG and non-HDL-C were not expected to be achieved at doses up to 320?mg monthly in patients with dyslipidemia.
  • ||||||||||  Evkeeza (evinacumab-dgnb) / Regeneron, Ultragenyx, vupanorsen (AKCEA-ANGPTL3-LRx) / Ionis, Pfizer
    Review, Journal:  Angiopoietin-like 3: An important protein in regulating lipoprotein levels. (Pubmed Central) -  Apr 18, 2023   
    Here, we review the discovery of ANGPTL3 as an important regulator of lipoprotein metabolism, molecular characteristics of the protein, mechanisms by which it regulates plasma lipids, and the clinical development of anti-ANGPTL3 agents. The clinical success of therapies inhibiting ANGPTL3 highlights the importance of this target as a novel approach in treating refractory hypertriglyceridemia and hypercholesterolemia.
  • ||||||||||  Evkeeza (evinacumab-dgnb) / Regeneron, Ultragenyx, ARO-ANG3 / Arrowhead, vupanorsen (AKCEA-ANGPTL3-LRx) / Ionis, Pfizer
    Journal:  Lipid metabolism and the targeting of angiopoietin-like 3: Experimental drugs under development. (Pubmed Central) -  Feb 9, 2023   
    The clinical success of therapies inhibiting ANGPTL3 highlights the importance of this target as a novel approach in treating refractory hypertriglyceridemia and hypercholesterolemia. No abstract available
  • ||||||||||  Evkeeza (evinacumab-dgnb) / Regeneron, Ultragenyx, vupanorsen (AKCEA-ANGPTL3-LRx) / Ionis, Pfizer
    Review, Journal:  How ANGPTL3 Inhibition Will Help Our Clinical Practice? (Pubmed Central) -  Jan 7, 2023   
    Finally, we will examine the lipid-lowering potential of pharmacological inhibition of ANGPTL3 based on the results of clinical trials employing Evinacumab, the first approved fully humanized monoclonal antibody against ANGPTL3. The future perspectives for ANGPTL3 inhibition will also be revised.
  • ||||||||||  vupanorsen (AKCEA-ANGPTL3-LRx) / Ionis, Pfizer
    HEPATIC FAT CHANGES AFTER AN ANTISENSE OLIGONUCLEOTIDE THERAPY TARGETING ANGPTL3: A TRANSLATE-TIMI 70 ANALYSIS (Poster Hall_Hall F) -  Jan 4, 2023 - Abstract #ACCWCC2023ACC_WCC_5975;    
    Vupanorsen caused increases in HFF that were associated with dose and with the degree of ANGPTL3 inhibition even after adjusting for dosing regimen. These findings suggest that hepatic fat will be important to evaluate for future therapies targeting ANGPTL3, especially those that work intracellularly.
  • ||||||||||  Review, Journal:  Recent Advances in Gene Therapy for Familial Hypercholesterolemia: An Update Review. (Pubmed Central) -  Nov 27, 2022   
    With gene editing technologies, such as CRISPR-Cas 9 and meganuclease, completing animal experiments in mice or cynomolgus monkeys and demonstrating lasting lipid-lowering effects, patients with FH are expected to reach a permanent cure in the future. (4) Gene therapy is being widely used for the lipid-lowering treatment of FH patients and has shown excellent therapeutic promise, but the current delivery efficiency, economic burden, immunogenicity and the precision of gene therapy can be further optimized.
  • ||||||||||  Review, Journal:  The promising novel therapies for familial hypercholesterolemia. (Pubmed Central) -  Jul 17, 2022   
    (4) Gene therapy is being widely used for the lipid-lowering treatment of FH patients and has shown excellent therapeutic promise, but the current delivery efficiency, economic burden, immunogenicity and the precision of gene therapy can be further optimized. While the therapies based on different targets including protein, RNA, and DNA are on different stages of development, the mechanisms of these novel therapies may provide new ideas for precision medicine.
  • ||||||||||  Journal:  Advances in the care of lipodystrophies. (Pubmed Central) -  Apr 26, 2022   
    However, these treatments are not yet approved for use in lipodystrophy. Further study of their efficacy and safety in this patient population is needed.
  • ||||||||||  vupanorsen (AKCEA-ANGPTL3-LRx) / Ionis, Pfizer
    Trial completion:  A Dose-Ranging Study With Vupanorsen (TRANSLATE-TIMI 70) (clinicaltrials.gov) -  Jan 11, 2022   
    P2b,  N=286, Completed, 
    Although limited, these results suggest that targeting ANGPTL3 with vupanorsen could address several metabolic abnormalities in patients with FPLD. Active, not recruiting --> Completed
  • ||||||||||  Parmodia (pemafibrate) / Kowa
    Journal:  Atherosclerosis prevention: new therapeutic strategies on the horizon (Pubmed Central) -  Nov 5, 2021   
    We discuss the mechanism of action, biological effects, and safety profile of these new drugs (bempedoic acid, lomitapide, inclisiran, evinacumab, vupanorsen, mipomersen, eicosapent ethyl, volanesorsen, pemafibrate, AKCEA-APO(a)-LRx, colchicine, semaglutide). Lastly, we briefly report therapeutic interventions based on biotechnological methods that could be implemented in the near future.
  • ||||||||||  Parmodia (pemafibrate) / Kowa
    Journal:  Triglycerides and cardiovascular disease. (Pubmed Central) -  Jun 30, 2021   
    Further studies with newer agents are required to determine the place of TG-lowering drugs in therapeutic pathways. Trials with agents such as pemafibrate and vupanorsen may finally answer these questions.
  • ||||||||||  vupanorsen (AKCEA-ANGPTL3-LRx) / Ionis, Pfizer
    Enrollment closed:  A Dose-Ranging Study With Vupanorsen (TRANSLATE-TIMI 70) (clinicaltrials.gov) -  May 19, 2021   
    P2b,  N=260, Active, not recruiting, 
    Trials with agents such as pemafibrate and vupanorsen may finally answer these questions. Recruiting --> Active, not recruiting