Odevixibat may reduce pruritus in kids with progressive familial intrahepatic cholestasis: Lancet

A new study conducted by Richard J Thompson and team it was found that in children with progressive familial intrahepatic cholestasis (PFIC), odevixibat reduced pruritus and serum bile acids more efficiently than placebo and was usually well tolerated. The findings of this study were published in The Lancet Gastroenterology and Hepatology.

Progressive familial intrahepatic cholestasis is a series of inherited pediatric liver disorders caused by abnormalities in bile secretion genes. The purpose of this study was to compare the effects of odevixibat, an ileal bile acid transporter inhibitor, to placebo in children with PFIC.

Patients who were diagnosed with PFIC1 or PFIC2 who had pruritus and increased serum bile acids at screening were eligible for this 24-week, randomized, double-blind, phase 3 research. Using an interactive web-based approach, patients were randomly randomised (1:1:1) to once-daily oral placebo, odevixibat 40 g/kg, or odevixibat 120 g/kg. Patients, doctors, and study personnel were all blinded to therapy allocation; randomization was done in six-block increments and stratified by PFIC type and patient age. Patients were enrolled at one of 33 global study locations. The proportion of patients with positive pruritus evaluations at week 24 and the proportion of patients with serum bile acid response at week 24 were the primary outcomes studied. Efficacy and safety were evaluated in patients who were randomly assigned to receive one or more doses of the study medication.

The key findings of this study were as follow:

1. Between June 21, 2018, and February 10, 2020, 62 patients were randomly assigned to one of three treatment groups: placebo (n=20), odevixibat 40 g/kg per day (n=23), or odevixibat 120 g/kg per day (n=19).

2. The mean fraction of PPAs was considerably greater with odevixibat versus placebo in a model-adjusted (least squares) analysis.

3. The percentage of patients who responded to odevixibat versus placebo was likewise significantly higher.

4. Diarrhea or frequent bowel movements and fever were the most prevalent treatment-emergent adverse events (TEAEs); significant TEAEs occurred in three (7%) of 42 odevixibat-treated individuals and five (25%) of 20 placebo-treated patients.

In conclusion, in patients with PFIC, odevixibat, delivered as once-daily oral capsules, is a non-surgical, pharmaceutical approach for interrupting the enterohepatic circulation.

Reference:

Thompson, R. J., Arnell, H., Artan, R., Baumann, U., Calvo, P. L., Czubkowski, P., Dalgic, B., D'Antiga, L., Durmaz, Ö., Fischler, B., Gonzalès, E., Grammatikopoulos, T., … Horn, P. (2022). Odevixibat treatment in progressive familial intrahepatic cholestasis: a randomised, placebo-controlled, phase 3 trial. In The Lancet Gastroenterology & Hepatology. Elsevier BV. https://doi.org/10.1016/s2468-1253(22)00093-0