From clinical development to real-world outcomes with inclisiran
File(s)
Author(s)
Connolly, Derek L
Sharma, Vinoda
Ray, Kausik K
Type
Journal Article
Abstract
Purpose of review
Inclisiran is a small interfering RNA that blocks hepatocyte production of the PCSK9 (proprotein convertase subtilisin/kexin type 9) protein by specifically targeting PCKS9 mRNA in the cytoplasm. This results in reduced degradation of LDL receptors and thus lowers LDL cholesterol by around 50% in addition to other lipid-lowering therapies. beyond 6 years of therapy. This review covers the latest published data and outlines future studies currently in process.
Recent findings
To date, half a million doses have been given worldwide with no untoward adverse events thus far. The twice-yearly injections make it potentially very user-friendly. The large phase 3a trials saw no diminution of effect with time up to nearly 7 years. Very large phase 3b randomized controlled trials are underway and may produce significant reductions in major adverse cardiovascular events
Summary
Inclisiran has been evaluated in numerous trials, primarily the ORION 926, ORION 1027 and ORION 1128 studies, which demonstrated that in patients already on maximally tolerated statin therapy, biannual inclisiran injections reduced LDL cholesterol by up to 52% compared to placebo with a good safety profile. The only observed side effects were mild and transient at the injection site. As mentioned in the accompanying video, this adds to our armamentarium of lipid treatments.
Inclisiran is a small interfering RNA that blocks hepatocyte production of the PCSK9 (proprotein convertase subtilisin/kexin type 9) protein by specifically targeting PCKS9 mRNA in the cytoplasm. This results in reduced degradation of LDL receptors and thus lowers LDL cholesterol by around 50% in addition to other lipid-lowering therapies. beyond 6 years of therapy. This review covers the latest published data and outlines future studies currently in process.
Recent findings
To date, half a million doses have been given worldwide with no untoward adverse events thus far. The twice-yearly injections make it potentially very user-friendly. The large phase 3a trials saw no diminution of effect with time up to nearly 7 years. Very large phase 3b randomized controlled trials are underway and may produce significant reductions in major adverse cardiovascular events
Summary
Inclisiran has been evaluated in numerous trials, primarily the ORION 926, ORION 1027 and ORION 1128 studies, which demonstrated that in patients already on maximally tolerated statin therapy, biannual inclisiran injections reduced LDL cholesterol by up to 52% compared to placebo with a good safety profile. The only observed side effects were mild and transient at the injection site. As mentioned in the accompanying video, this adds to our armamentarium of lipid treatments.
Date Issued
2024-12-01
Date Acceptance
2024-12-01
Citation
Current Opinion in Lipidology, 2024, 35 (6), pp.281-289
ISSN
0957-9672
Publisher
Lippincott, Williams & Wilkins
Start Page
281
End Page
289
Journal / Book Title
Current Opinion in Lipidology
Volume
35
Issue
6
Copyright Statement
Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved. This is the author’s accepted manuscript made available under a CC-BY licence in accordance with Imperial’s Research Publications Open Access policy (www.imperial.ac.uk/oa-policy)
License URL
Identifier
https://www.ncbi.nlm.nih.gov/pubmed/39331729
PII: 00041433-990000000-00091
Subjects
Biochemistry & Molecular Biology
Cardiovascular System & Cardiology
Endocrinology & Metabolism
EVOLOCUMAB
FAMILIAL HYPERCHOLESTEROLEMIA
inclisiran
INTERFERENCE
LDL cholesterol
LDL CHOLESTEROL
Life Sciences & Biomedicine
PCSK9
PCSK9 inhibition
Peripheral Vascular Disease
RISK
RNA
Science & Technology
STATIN
Publication Status
Published
Coverage Spatial
England
Date Publish Online
2024-12-01