Rationale and design of two trials assessing the efficacy, safety, and tolerability of inclisiran in adolescents with homozygous and heterozygous familial hypercholesterolaemia
Open accessAbstract
Background Inclisiran is a small interfering RNA molecule that reduces low-density lipoprotein cholesterol (LDL-C) by inhibition of proprotein convertase subtilisin/kexin type 9. This subcutaneous, twice-yearly administered agent has been shown to effectively and safely lower LDL-C in adult patients with established atherosclerotic cardiovascular disease, adults at high risk for atherosclerotic cardiovascular disease, as well as in adults with heterozygous familial hypercholesterolaemia. With the current, limited treatment options available to reach treatment goals in children with severe heterozygous familial hypercholesterolaemia, homozygous familial hypercholesterolaemia, or statin intolerance, inclisiran could be a valuable new therapeutic option. Objectives The objective of these ongoing studies is to investigate the efficacy, safety, and tolerability of inclisiran in adolescents diagnosed with homozygous familial hypercholesterolaemia (ORION-13) or heterozygous familial hypercholesterolaemia (ORION-16). Study design ORION-13 and ORION-16 are both two-part (1-year double-blind inclisiran vs. placebo/1 year open-label inclisiran) multicentre trials including adolescents aged 12 to Clinical trial registration https://www.clinicaltrials.gov/. Unique identifier: NCT04659863 (ORION-13) and NCT04652726 (ORION-16).
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Inclisiran improved multiple lipid parameters including non-HDL-C, apoB, triglycerides, and lipoprotein(a) in addition to LDL-C.
“Inclisiran improved multiple lipid parameters including non-HDL-C, apoB, triglycerides and lipoprotein(a) in addition to LDL-C which makes it beneficial for complete lipid management [39, 43, 49].”
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“Inclisiran improved multiple lipid parameters including non-HDL-C, apoB, triglycerides and lipoprotein(a) in addition to LDL-C which makes it beneficial for complete lipid management [39, 43, 49].”
- Authors
- Reijman, M. D., Schweizer, A., Peterson, A. L. H., Bruckert, E., Stratz, C., Defesche, J. C., Hegele, R. A., & Wiegman, A.
- Affiliations
- Amsterdam UMC Location University of Amsterdam (NL)
- Novartis (Switzerland) (CH)
- University of Wisconsin–Madison (US)
- Department of Endocrinology and Prevention of Cardiovascular Disease, Pitié-Salpêtrière University Hospital , Paris , France
- Western University (CA)
- Corresponding author
- Wiegman, Albert
- ORCID
- Venue
- European Journal of Preventive Cardiology
- Publisher
- Oxford University Press (OUP)
- Published
- 2022-02-17
- Volume
- 29
- Issue
- 9
- Pages
- 1361-1368
- ISSN
- 2047-4873 (ISSN-L)
- 2047-4881
- OpenAlex
- W4213370194
- Cited by
- 37
- References
- 8
- Citations by year
- 2026: 6 · 2025: 3 · 2024: 9 · 2023: 10 · 2022: 9
- FWCI
- 7.40
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- European Journal of Preventive Cardiology (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Data Archiving and Networked Services (DANS) (submittedVersion, other-oa)
- HAL (submittedVersion)
- Pure Amsterdam UMC (submittedVersion, cc-by)
- Funders
- Novartis Pharma AG
- Topics
- Health Sciences › Medicine › Surgery › Lipoproteins and Cardiovascular Health
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Lipid metabolism and disorders
- Health Sciences › Medicine › Surgery › Cholesterol and Lipid Metabolism
- Keywords
- inclisiran, familial hypercholesterolemia, homozygous familial hypercholesterolemia, heterozygous familial hypercholesterolemia, adolescents, LDL cholesterol lowering, PCSK9 inhibition, siRNA, lipid-lowering therapy, treatment-emergent adverse events, statin intolerance
- MeSH terms
- Adolescent, Adult, Anticholesteremic Agents, Cardiovascular Diseases, Child, Double-Blind Method, Humans, Hyperlipoproteinemia Type II, Cholesterol, LDL, Randomized Controlled Trials as Topic, RNA, Small Interfering
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