Efficacy, Safety and Tolerability of Volixibat, an IBAT Inhibitor, in Patients With Intrahepatic Cholestasis of Pregnancy.

Intrahepatic cholestasis of pregnancy (ICP) presents with cholestatic pruritus, elevated sBA and increased risk of adverse perinatal outcomes. Volixibat is a minimally absorbed IBAT inhibitor that interrupts enterohepatic recirculation. We describe four patients with ICP with pruritus and sBA > ULN treated with volixibat (20 or 80 mg BID orally until delivery), with dose modifications permitted for tolerability. Daily pruritus scores, sBA, liver enzymes, perinatal outcomes and TEAEs were assessed. Over 1000 patients were invited to participate; 26 were screened, and four received volixibat. Three patients experienced reductions in pruritus from baseline regardless of volixibat dose, with intermittent relief coinciding with resumption of dosing when doses were interrupted. sBA nadir values all reached < 6 μmol/L following volixibat. No clinically meaningful changes in laboratory parameters were observed. All patients had healthy live births. Most frequent TEAEs were gastrointestinal. Volixibat demonstrated improvements in pruritus and sBA in patients with ICP. Trial Registration: NCT04718961.