Volanesorsen is a synthetic antisense oligonucleotide (ASO) used as an active pharmaceutical ingredient for the treatment of severe hypertriglyceridemia associated with familial chylomicronemia syndrome (FCS). It is designed to selectively bind to messenger RNA encoding apolipoprotein C-III (apoC-III) and reduce its production.
Volanesorsen is marketed in Europe under the brand name Waylivra as volanesorsen sodium. The European Medicines Agency identifies volanesorsen sodium as the active substance. It is an antisense oligonucleotide consisting of 20 nucleotides with a phosphorothioate backbone and several 2′-O-(2-methoxyethyl) modified nucleotides.
The free-acid form of volanesorsen has the CAS Number 915430-78-3, molecular formula C230H320N63O125P19S19, and calculated molecular weight of approximately 7165 g/mol. The sodium salt has CAS Number 1573402-50-2 and is the pharmaceutical form used in Waylivra.
Volanesorsen is fundamentally different from conventional small-molecule APIs. It is a chemically synthesized antisense oligonucleotide designed to recognize a specific sequence of apoC-III mRNA.
The molecule contains a phosphorothioate backbone, which improves resistance to enzymatic degradation, together with modified sugar residues that enhance stability and pharmacological properties.
The 20-nucleotide sequence is designed to hybridize specifically with human APOC3 mRNA. Following binding, the antisense mechanism promotes degradation of the target RNA, reducing apoC-III protein production.
Because volanesorsen is an oligonucleotide, traditional small-molecule tests such as melting point, specific rotation, residue on ignition and conventional HPLC assay are not appropriate as universal release specifications.
Apolipoprotein C-III is an important regulator of triglyceride metabolism. Increased apoC-III can interfere with the clearance of triglyceride-rich lipoproteins.
Volanesorsen binds selectively to APOC3 mRNA. This leads to degradation of the target RNA and decreases synthesis of apoC-III.
Reduced apoC-III production can enhance the clearance of triglyceride-rich lipoproteins and reduce circulating triglyceride concentrations.
Volanesorsen is primarily associated with the treatment of familial chylomicronemia syndrome, a rare inherited disorder characterized by severely elevated triglyceride concentrations.
Its pharmaceutical applications include:
Volanesorsen contains 20 nucleotides and incorporates chemically modified nucleotides.
The molecule contains:
These modifications are important for improving nuclease resistance, pharmacological activity and biological stability.
Because volanesorsen is a complex oligonucleotide, its analytical characterization requires specialized techniques.
The EMA active-substance specification includes:
These controls are specifically described in the EMA assessment of the active substance.
For volanesorsen, purity is evaluated using chromatographic and mass-spectrometric methods appropriate for oligonucleotides.
The EMA assessment explains that impurities are controlled as groups rather than necessarily using the conventional individual-impurity approach used for small molecules. This includes degradation products and other oligonucleotide-related impurities.
This approach reflects the complexity of antisense oligonucleotide chemistry and the large number of closely related molecular species that can arise during synthesis or degradation.
Volanesorsen is produced using solid-phase oligonucleotide synthesis followed by deprotection, purification and appropriate downstream processing.
Critical manufacturing parameters can include:
The EMA assessment describes quality-by-design principles and process controls for the manufacture of volanesorsen active substance.
Volanesorsen sodium should be stored according to the validated pharmaceutical stability specification and protected from unsuitable temperature, moisture and environmental conditions.
As an oligonucleotide API, appropriate control of water content, microbial quality and container-closure integrity is important.
Volanesorsen is a specialized antisense oligonucleotide API intended for advanced pharmaceutical and biotechnology applications.
Swapnroop Drugs & Pharmaceuticals can position Volanesorsen API for qualified pharmaceutical, biotechnology and research customers involved in antisense oligonucleotide development, metabolic disease research and specialty pharmaceutical manufacturing.
| Parameter | Specification |
|---|---|
| Appearance | white to off-white crystalline powder |