Olezarsen is a chemically modified antisense oligonucleotide (ASO) designed to inhibit expression of apolipoprotein C-III (apoC-III) by targeting APOC3 mRNA. It is conjugated to a triantennary N-acetylgalactosamine (GalNAc3) ligand to promote selective uptake by hepatocytes. Olezarsen sodium is the active substance in TRYNGOLZA.
Olezarsen is a 20-nucleotide, single-stranded antisense oligonucleotide incorporating 2′-O-(2-methoxyethyl) (MOE) modifications and phosphorothioate linkages. The GalNAc3 conjugate facilitates hepatocyte delivery through the asialoglycoprotein receptor.
The US FDA identifies the active ingredient as olezarsen sodium, with molecular formula C₂₉₆H₄₁₉N₇₁O₁₅₄P₂₀S₁₉Na₂₀ and molecular weight 9,124.48 Da.
Olezarsen selectively binds to APOC3 mRNA, resulting in RNase H1-mediated degradation of the target mRNA. This reduces production of apoC-III, a protein involved in triglyceride metabolism and clearance of triglyceride-rich lipoproteins.
The GalNAc3 ligand enables preferential delivery of the oligonucleotide to hepatocytes by interacting with the hepatocyte-specific asialoglycoprotein receptor.
Olezarsen is an RNA-targeted therapeutic designed to reduce apoC-III production and triglyceride levels. In the European Union, TRYNGOLZA (olezarsen) received marketing authorization on 17 September 2025 for use with diet in adults with genetically confirmed familial chylomicronaemia syndrome (FCS).
Because olezarsen is an oligonucleotide-GalNAc conjugate, conventional small-molecule API tests such as melting point, specific rotation and residue on ignition are not the most meaningful primary quality attributes.
Appropriate analytical characterization can include:
The FDA description confirms the detailed chemical architecture of olezarsen sodium, including the MOE-modified ASO, phosphorothioate linkages and GalNAc conjugate.
TRYNGOLZA contains olezarsen sodium as the active ingredient. Current US labeling describes single-dose autoinjectors containing 50 mg or 80 mg of olezarsen, corresponding to 53 mg or 84 mg of olezarsen sodium, respectively, in 0.8 mL solution. The finished formulation has a pH adjusted between 6.9 and 7.9.
| Parameter | Specification |
|---|---|
| Appearance | White crystalline powder or crystals |
| Identification | IR & HPLC compliant |
| Assay (HPLC) | 98.0% – 102.0% |
| Loss on Drying | NMT 0.5% |
| Residue on Ignition | NMT 0.1% |
| Heavy Metals | NMT 10 ppm |
| pH (1% Solution) | 5.0 – 7.0 |
| Individual Impurity | NMT 0.5% |
| Water Content | NMT 0.5% |