Nedosiran is a chemically modified small interfering RNA (siRNA) therapeutic designed to reduce the production of oxalate in patients with primary hyperoxaluria type 1 (PH1). It is a liver-targeted RNA interference medicine that uses a GalNAc conjugate to facilitate delivery to hepatocytes.
Nedosiran targets lactate dehydrogenase A (LDHA) messenger RNA in the liver. By reducing LDHA expression, it decreases the conversion of glyoxylate to oxalate and thereby lowers hepatic oxalate production.
Nedosiran is a specialized oligonucleotide-based pharmaceutical active ingredient used in RNA interference and rare-disease pharmaceutical development.
Unlike conventional small-molecule APIs, Nedosiran is a highly complex, chemically modified double-stranded RNA molecule. Important quality attributes include identity, purity, sequence integrity, oligonucleotide-related impurities, double-stranded RNA characteristics, residual solvents/reagents, elemental impurities, endotoxin, bioburden and product-specific physicochemical parameters.
API Name: Nedosiran Sodium
CAS Number: 2247026-22-6
Molecular Formula: C662H808F19N231O413P57S6Na57
Molecular Weight: Approximately 22,238 Da
Molecule Type: Synthetic small interfering RNA (siRNA)
Therapeutic Class: RNA interference therapeutic
Target: Lactate Dehydrogenase A (LDHA)
Therapeutic Area: Rare Diseases / Metabolic Disorders
Dosage Form Association: Subcutaneous injection
The USAN record identifies nedosiran sodium by CAS 2247026-22-6 and gives the molecular formula C662H865F19N231O413P57S6Na57 in its naming documentation; pharmaceutical references report the molecular weight at approximately 22.2 kDa.
Nedosiran uses the RNA interference pathway to reduce expression of LDHA mRNA in hepatocytes.
Its activity involves:
LDHA catalyzes the final common step in hepatic oxalate production, making it an important target for RNAi-based treatment of PH1.
Nedosiran is associated with:
Nedosiran is marketed as RIVFLOZA and is indicated to lower urinary oxalate levels in eligible patients with PH1.
Nedosiran sodium is a complex oligonucleotide pharmaceutical substance rather than a conventional crystalline small molecule. Commercial and research presentations can therefore differ depending on whether the material is supplied as a formulated aqueous solution or as a drug-substance preparation.
For pharmaceutical characterization, molecular weight, purity, sequence identity, oligonucleotide integrity, aggregation/related species and solution characteristics are more relevant than conventional small-molecule parameters such as melting point.
Nedosiran manufacturing involves specialized oligonucleotide synthesis and downstream purification processes. Depending on the manufacturing platform, critical stages may include:
Typical quality evaluation for a complex siRNA API may include:
Exact acceptance limits should be taken from the applicable validated drug-substance or drug-product specification.
Nedosiran should be stored according to the validated stability and handling requirements established for the particular drug substance or formulation. Temperature, light exposure, container closure and freeze/thaw conditions should be controlled according to the approved product specification.
Nedosiran is relevant to research involving:
| 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% |
| Individual Impurity | NMT 0.5% |
| Total Impurities | NMT 1.0% |
| Water Content | NMT 0.5% |