The site of the Media Sphera Publishers contains materials intended solely for healthcare professionals.
By closing this message, you confirm that you are a certified medical professional or a student of a medical educational institution.

Sumarokov A.B.

National Medical Research Centre of Cardiology

Inclisiran — lipid-lowering drug using RNA therapy. Hypolipidemic potential

Authors:

Sumarokov A.B.

More about the authors

Journal: Russian Cardiology Bulletin. 2022;17(4): 32‑37

Read: 22290 times


To cite this article:

Sumarokov AB. Inclisiran — lipid-lowering drug using RNA therapy. Hypolipidemic potential. Russian Cardiology Bulletin. 2022;17(4):32‑37. (In Russ.)
https://doi.org/10.17116/Cardiobulletin20221704132

Recommended articles:

References:

  1. Agarwal N, Dasaraghi PVN, Mohmmed A, Malhotra P, Bhatnagar RK, Mukherjee SK. RNA Interference: Biology, Mechanism, and Applications. Microbiology and Molecular Biology Reviews. 2003;67(4):657-685.  https://doi.org/10.1128/MMDR.67.4.657-685.2003
  2. Afanasjeva OI, Pokrovsky SN. Lipid metabolism correction by antisens technology. Rational Pharmacotherapy in Cardiology. 2013;9(5):532-541. (In Russ.).
  3. Afanasjeva OI, Ezhov MV, Pokrovsky SN. Antisens oligonucleotides and therapeutical monoclonal antibodies as a basement for novel biological lipidlowering drugs. Russian Journal of Cardiology. 2018;23(8):99-109. (In Russ.). https://doi.org/10/15829/1560-4071-2018-8-99-109
  4. Lamb YN. Inclisiran: First Approval. Drugs. 2021;81(3):389-395.  https://doi.org/10.1007/s40265-021-01473-6
  5. Voevoda MI, Gurevich VS, Ezhov MV, Sergienko IV. Inclisiran — a new era in lipid lowering therapy. Kardiologiia. 2022;62(6):57-62. (In Russ.). https://doi.org/10.1018087/cardio.2022.6.n2115
  6. Bellosta S, Rossi C, Alieva AS, Catapano AL, Corsini A, Baragetti A. Cholesterol Lowering Biotechnological Strategies: A preclinical perspective review. Cardiovascular Drugs and Therapy. 2022. https://doi.org/10.1007/s10557-021-07293-w
  7. Friedrich M, Aigner A. Therapeutic siRNA: State-of-the Art and Future Perspectives. BioDrugs. 2022;36(5):549-571.  https://doi.org/10.1007/s40259-022-00549-3
  8. Zhou Y, Teng P, Montgometry NT, Li X, Tang W. Development of Triantennary N-acetylgalactosamine Conjugates as Degraders for Extracellular Proteins. ACS Central Science. 2021;7(3):499-506.  https://doi.org/10.1021/acscentsci.1c00146
  9. U.S. Food and Drug Administration. FDA Approves Add-On Therapy to Lower Cholesterol Among Certain High-Risk Adults. 2021. www/fda.gov/drugs/news-events-human—drugs/fda approves- add-therapy- lower —cholesterol-among-certain-high-risk-adults/2022
  10. Fitzgerald K, Frank-Kamenetsky M, Shulga-Morskaya S, Liebow A, Bettencourt BR, Sutherland JE, Hutabarat RM, Clausen VA, Karsten V, Cehelsky J, Nochur SV, Kotelianski V, Horton J, Mant T, Chiesa J, Ritter J, Munisamy M, Vaishnaw AK, Gollob JA, Simon A. Effect of an RNA interference drug on the synthesis of propronein convertase subtilinsin/kexin type 9 (PCSK9) and concentrationof serum LDL cholesterol in healthy volunteers: a randomized, single-blind, placebo-controlled, phase 1 trial. Lancet. 2014;383(9911):60-68.  https://doi.org/10.1016/S0140-6736
  11. Fitzgerald K, White S, Borodovsky A, Bettencourt BR, Strahs A, Clausen V, Wijngaard P, Horton JD, Taubel J, Brooks A, Fernando C, Kauffman RS, Kallend D, Vaishnaw A, Simon A. A Highly Durable RNAi Therapeutic Inhibitor of PCSK9. New England Journal of Medicine. 2017;376(1):41-51.  https://doi.org/10.1056/NEJMoa1609243
  12. Ray KK, Landmesser U, Leiter LA, Kallend D, Dufour R, Karakas M, Hall T, Troquay RPT, Turner T, Visseren FLJ, Wijngaard P, Wright RS, Kastelein JJP. Inclisiran in Patients at High Cardiovascular Risk with Elevated LDL Cholesterol. New England Journal of Medicine. 2017;376:1430-1440. https://doi.org/10/1056/NEJMoa1615758
  13. Ray KK, Stoekenbroek R, Kallend D, Nishikido T, Leiter LA, Landmesser U, Wright RS, Wijngaard PLJ, Kastelein JJP. Effect of 1 or 2 Doses of Inclisiran on Low Density Cholesterol Levels. One-Year Follow-Up of the ORION-1 Randomized Clinical Trial. JAMA Cardiology. 2019;4(11):1067-1075. https://doi.org/10.1001/jamacardio.2019.3502
  14. Bangalore S, Fayyad R, Messeri FH, Laskey R, DeMicco DA, Kastelein JJP, Waters DD. Relation of Variability of Low-Density Lipoprotein Cholesterol and Blood Pressure to Events in Patients With Previous Myocardial Infarction from the IDEAL Trial. American Journal of Cardiology. 2017;119(3):379-387.  https://doi.org/10.1016/j.jamjcard.2916.10.037
  15. Landmesser U, Haghikia A, Leiter LA, Wright RS, Kallend D, Wijngaard P, Stoekenbroek R, Kastelein JJ, Ray KK. Effect of inclisiran, the small- interfering RNA against proprotein convertase subtilin/kexin type9, on platelets, immune cells, and immunological biomarkers: a pre-specified analysis from ORION-1. Cardiovascular Research. 2021;117:284-291.  https://doi.org/10.1093/cvr/cvaa077
  16. Warden BA, Duell PB, Inclisiran: A Novel Agent for Lowering Apolipoprotein B-containing Lipoproteins. Journal of Cardiovascular Pharmacology. 2021;78(2):157-174.  https://doi.org/10.1097/FJC.0000000000001053
  17. Michail N. Update on Inclisiran for Treatment of Hypercholesterolemia. Journal of Diabetes Research Reviews & Reports. 2020;2(2):1-3.  https://doi.org/10.47363/JDRR/2020(2)106
  18. Wright RS, Collins MG, Stoekenbroek RM, Robson R, Wijngaard PLJ, Landmesser U, Leiter LA, Kastelein JJP, Ray KK, Kallend D. Effect of Renal Impairment on the Pharmacokinetics, Efficacy, and Safety of Inclisiran: An Analysis of the ORION-7 and ORION-1 Studies. Mayo Clinic Proceedings. 2020;95(1):77-89.  https://doi.org/10.1016/j.mayocp.2019.08.021
  19. Kallend D, Stoekenbroek R, He YL, Smith PF, Wijngaard P. Pharmacokinetics and Pharmacodynamics of Inclisiran, a smoll interfering RNA therapy, in patients with hepatic impairment. Clinical Cardiology. 2022;16(2):208-219.  https://doi.org/10.1016/j.jacl.2022.01.001
  20. Kosmas CE, Estrella AM, Skavdis A, Genao EP, Martinez I, Guzman E. Inclisiran for Treatment of Cardiovascular Disease: S Short Review on the Emerging Data and Therapeutic Potencial. Therapeutics and Clinical Risk Management. 2020;16:1031-1037. https://doi.org/10.2147/TCRM.S230592
  21. Raal FJ, Kallend D, Ray KK, Turner T, Koenig W, Wright RS, Wijngaard PLJ, Curcio D, Jaros MJ, Leiter LA, Kastelein JJP, for the ORION-9 Investigators. Inclisiran for Treatment of Heterozygous Familial Hypercholesterolemia. New England Journal of Medicine. 2020;382(16):1520-1530. https://doi.org/10.1056/NEJMoa1913805
  22. Ray KK, Wright RS, Kallend D, Koenig W, Leiter LA, Raal FJ, Bisch JA, Richardson T, Jaros M, Wijngaard PLJ, Kastelein JJP, ORION-10 and ORION-11 Investigators. Two Phase 3 Trials of Inclisiran in Patients with Elevated LDL Cholesterol. New England Journal of Medicine. 2020;382(16):1507-1519. https://doi.org/10.1056/NEJMoa1912387
  23. Wright RS, Ray KK, Kallend DG, Jaros M, Koenig W, Leiter LA, Landmesser U, Schwartz GG, Friedman A, Wijngaard PLJ, Conde GL, Kastelein JJP, ORION Phase III Investigators. Pooled Patient-Level Analysis of Inclisiran Trials in Patients With Familial Hypercholesterolemia or Atherosclerosis. JACC. 2021;77(9):1182-1193. https://doi.org/10.1016/j.jacc.2021.12.058
  24. Howing GK, Lepor NE, Kallend D, Stoekenbroek RM, Wijngaard PLJ, Raal FJ. Inclisiran durably lowers low-density lipoprotein cholesterol and proprotein convertase subtilin/kexin type 9 expression in homozygous familial hypercholesterolemia: the ORION-2 pilot study. Circulation. 2020;141(22):1829-1831. https://doi.org/10.1161/CIRCULATIONAHA.119.044431
  25. ClinicalTriqals.gov. A Study of Inclisiran in Participants With Homozygous Familial Hypercholesterolemia (HoFM) (ORION-5). clinicaltrials.gov/ct2/show/NCT03851705
  26. Raijman MD, Schweizer A, Peterson ALH, Bruckert E, Stratz C, Defesche JC, Hegele RA, Wiegman A. Rationale and design of two trials assessing the efficace, safety, and tolerability of inclisiran in adolescents with homozygous familial hypercholesterolemia. European Journal of Preventive Cardiology. 2022;29(9):1361-1368. https://doi.org/10.1093/eurjpc/zwac025
  27. European Medicines Agency. Leqvio 284 mg solution for injection in pre-filled syringe: summary of product characteristics. 2021; Ema.europa.eu 
  28. ClinicalTrials.gov. NCT0503428, Study of Inclisiran to Prevent Cardiovascular (CV) Events in Partisipants with Established Cardiovascular Disease (VICTORION-2P).
  29. Scicchitano P, Milo M, Mallamamaci R, De Palo M, Caldarola P, Massari F, Gabrielli D, Colivicchi F, Ciccone MM. Inclisiran in lipid mahagement: A Literature overview and future perspectives. Biomedicine & Pharmacology. 2021;143:112227. https://doi.org/10.1016/j.biopha.2021.112227
  30. Khan SA, Naz A, Masood MQ, Shah R. Meta-Analysis of Inclisiran for the Treatment of Hypercholesterolemia. The American Journal of Cardiology. 2020;134:69-73.  https://doi.org/10.1016/j.amjcard.2020.08.018
  31. Pirillo A, Catapano AL. Inclisiran: How Widely and When Should We Use It? Current Atherosclerosis Reports. 2022;24(10):803-811.  https://doi.org/10.1007/s11883-022-01056-0

Email Confirmation

An email was sent to test@gmail.com with a confirmation link. Follow the link from the letter to complete the registration on the site.

Email Confirmation

We use cооkies to improve the performance of the site. By staying on our site, you agree to the terms of use of cооkies. To view our Privacy and Cookie Policy, please. click here.