From clinical development to real-world outcomes with inclisiran
Sharma, Vinoda Ray, Kausik K
Sharma, Vinoda
Ray, Kausik K
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Sandwell and West Birmingham NHS Trust; University of Birmingham; Imperial College
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Publication date
2024-09-30
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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.
Citation
Connolly DL, Sharma V, Ray KK. From clinical development to real-world outcomes with inclisiran. Curr Opin Lipidol. 2024 Sep 30. doi: 10.1097/MOL.0000000000000954. Epub ahead of print
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Article