Odevixibat is a small-molecule ileal bile acid transporter (IBAT) inhibitor developed for the treatment of cholestatic liver diseases. It inhibits the reabsorption of bile acids in the terminal ileum, thereby reducing the enterohepatic circulation of bile acids.
The pharmaceutical substance is formulated as odevixibat sesquihydrate, a crystalline hydrate containing 1.5 molecules of water. Current U.S. labeling gives the molecular formula as C₃₇H₄₈N₄O₈S₂ × 1.5H₂O and molecular weight as 768.0 g/mol, while the anhydrous molecular weight is 740.9 g/mol.
EMA confirms that odevixibat sesquihydrate is a white to off-white hygroscopic crystalline solid and that the active substance has two chiral centres.
Odevixibat has the molecular formula C₃₇H₄₈N₄O₈S₂ in its anhydrous form and a calculated molecular weight of 740.9 g/mol. The commercial pharmaceutical form is the sesquihydrate with molecular weight 768.0 g/mol.
EMA reports that odevixibat exhibits pH-dependent solubility, with the substance being insoluble at pH 1–4 and having maximum solubility around neutral pH. The substance also exhibits polymorphism, with one stable form routinely produced in the commercial manufacturing process.
Odevixibat is a reversible inhibitor of IBAT, the transporter responsible for reabsorbing bile acids in the terminal ileum. Inhibition of IBAT decreases intestinal bile-acid reabsorption and reduces the return of bile acids to the liver through the enterohepatic circulation.
Odevixibat is the active substance in Bylvay. EMA currently identifies Bylvay as an authorized medicine containing odevixibat for treatment of progressive familial intrahepatic cholestasis (PFIC) in patients from 6 months of age.
Odevixibat requires control of chemical purity, stereochemistry, polymorphic form and hydrate state. EMA reports the use of:
EMA specifically notes that chiral purity is controlled by chiral HPLC and that the polymorphic form and particle size are controlled in the active-substance specification.
| 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 0.15% |
| Water Content | NMT 0.5% |