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

## TL;DR

Volixibat, a drug for intrahepatic cholestasis of pregnancy, reduced itching and bile acid levels in most patients, with mild side effects and no drug detected in maternal blood.

## Contribution

Volixibat shows efficacy and safety in treating intrahepatic cholestasis of pregnancy with minimal systemic absorption.

## Key findings

- Volixibat reduced serum bile acid levels below 6 μmol/L in all patients.
- Most participants experienced improved pruritus with treatment.
- The main adverse event was diarrhea, which improved with dose reduction.

## Abstract

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

Volixibat treatment for ICP resulted in reduced serum bile acid concentrations and improvement in pruritus in the majority of study participants.The main adverse event was diarrhoea that improved with reduction of volixibat dose.No drug was detected in maternal blood.

Volixibat treatment for ICP resulted in reduced serum bile acid concentrations and improvement in pruritus in the majority of study participants.

The main adverse event was diarrhoea that improved with reduction of volixibat dose.

No drug was detected in maternal blood.