Olezarsen: First Approval

  

Declarations

Funding The preparation of this review was not supported by any external funding.

Authorship and Conflict of interest Yahiya Y. Syed is a salaried employee of Adis International Ltd/Springer Nature, and declares no relevant conflicts of interest. All authors contributed to the review and are responsible for the article content.

Ethics approval, Consent to participate, Consent to publish, Availability of data and material, Code availability not applicable

Additional information about this Adis Drug Review can be found here

Abstract

Olezarsen (TRYNGOLZA™) is a first-in-class, GalNAc3-conjugated antisense oligonucleotide being developed by Ionis Pharmaceuticals for the treatment of familial chylomicronaemia syndrome (FCS) and severe hypertriglyceridaemia. It binds to apoC-III mRNA, promoting its degradation and lowering serum apoC-III protein levels. This action lowers triglyceride levels by enhancing the clearance of plasma triglyceride-rich lipoproteins such as chylomicrons and very-low-density lipoproteins. GalNAc3 conjugation improves hepatocyte uptake, which helps localise oligonucleotide treatment to the liver; this enables lower dosing, reduced injection volume and frequency, potentially reducing the risk of adverse events such as thrombocytopenia. Olezarsen received its first approval in the USA on 19 December 2024 under priority review as an adjunct to diet to reduce triglycerides in adults with FCS. This article summarizes the milestones in the development of olezarsen leading to this first approval for FCS.

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