Plozasiran is a chemically synthesized, hepatocyte-targeted small interfering RNA (siRNA) pharmaceutical active ingredient designed to reduce apolipoprotein C-III (APOC3) expression through RNA interference. The pharmaceutical product contains plozasiran present as plozasiran sodium. Plozasiran sodium is identified by CAS Number 2379776-41-5, molecular formula C₄₉₃H₆₁₁F₁₁N₁₆₄Na₄₃O₃₁₁P₄₃S₇, and molecular weight 16,563.98 Da.
Plozasiran API is a double-stranded siRNA containing chemically modified ribonucleotides and a covalently attached ligand containing three N-acetylgalactosamine (GalNAc) residues. The GalNAc ligand facilitates selective delivery of the siRNA to hepatocytes. The RNA strands contain 2'-fluoro and 2'-O-methyl modifications together with phosphorothioate linkages.
Plozasiran is also known by the development designation ADS-005 and the synonym ARO-APOC3. FDA GSRS identifies plozasiran as the active moiety and plozasiran sodium as the corresponding sodium substance.
Plozasiran is a complex oligonucleotide therapeutic rather than a conventional small-molecule API. Plozasiran sodium contains two complementary RNA strands with chemically modified nucleotides and multiple phosphorothioate linkages. The sodium substance has a molecular formula of C₄₉₃H₆₁₁F₁₁N₁₆₄Na₄₃O₃₁₁P₄₃S₇ and molecular weight of 16,563.98 Da.
Key identifiers include:
FDA identifies plozasiran sodium as the active pharmaceutical substance and states that it is freely soluble in water.
Plozasiran is an APOC3-directed siRNA therapeutic. By reducing APOC3 mRNA in hepatocytes, it reduces production of apolipoprotein C-III, a protein involved in triglyceride metabolism.
The FDA approved REDEMPLO (plozasiran) in November 2025 as an adjunct to diet to reduce triglyceride levels in adults with familial chylomicronemia syndrome (FCS).
The European Union subsequently authorized Redemplo in June 2026 for the same therapeutic indication.
Potential pharmaceutical and development applications include:
Plozasiran requires an analytical strategy appropriate for a chemically modified siRNA rather than conventional small-molecule API testing.
Relevant analytical techniques include reverse-phase HPLC, ion-pair HPLC, size-exclusion chromatography, LC-MS, mass spectrometry, UV analysis, sequence/structural characterization and other oligonucleotide-specific analytical methods.
FDA's chemistry review identifies API assay and degradation impurities as critical quality attributes and states that these are controlled using validated analytical methods. The FDA review also reports that stability data supported an approved 2-year shelf life.
A current research-grade plozasiran sodium reference product reports 99.98% assay/purity, but this is a commercial research-product value and should not be represented as the FDA commercial API acceptance criterion.
Plozasiran API is identified as plozasiran sodium, CAS 2379776-41-5, with molecular formula C₄₉₃H₆₁₁F₁₁N₁₆₄Na₄₃O₃₁₁P₄₃S₇ and molecular weight 16,563.98 Da.
Because plozasiran is a chemically modified siRNA, quality evaluation requires control of sequence identity, duplex integrity, chemical modifications, assay/content, purity, degradation products, residual process-related materials and microbiological attributes as applicable.
Plozasiran sodium should be packaged using suitable moisture-protective containers and handled under controlled conditions appropriate for a chemically modified oligonucleotide.
A current research-grade plozasiran sodium product recommends −20°C storage in sealed conditions away from moisture. For pharmaceutical API material, commercial storage conditions should follow validated stability data and the approved product specification.
The FDA-approved drug product has an approved shelf life of 2 years under its labeled storage conditions.
Applicable documentation may include:
Plozasiran is a next-generation, hepatocyte-targeted siRNA therapeutic with a defined molecular architecture and established clinical and regulatory application. Its pharmaceutical form is plozasiran sodium, CAS 2379776-41-5, with a molecular weight of 16,563.98 Da.
Its GalNAc-mediated hepatocyte targeting, chemically modified RNA strands and phosphorothioate linkages require specialized analytical and quality-control approaches. The FDA's review specifically recognizes assay and degradation impurities as important quality attributes for plozasiran sodium.
| Parameter | Specification |
|---|---|
| Appearance | white to off-white crystalline powder |
| Identification | IR & HPLC compliant |
| Assay (HPLC) | 99.98% |
| Loss on Drying | NMT 0.5% |
| Residue on Ignition | NMT 0.1% |
| Individual Impurity | NMT 0.5% |
| Water Content | NMT 0.5% |