Odevixibat reduces markers of progressive familial intrahepatic cholestasis in children

Odevixibat treatment reduced levels of peripheral blood autotaxin, pruritus and serum bile acid among pediatric patients with progressive familial intrahepatic cholestasis, according to pooled data.

“Progressive familial intrahepatic cholestasis, or PFIC, is a group of rare genetic liver diseases characterized by chronic cholestasis, high serum bile acids and severe pruritis being the hallmarks of the disease and progressive liver disease. Lysophosphatidic acid mainly produced by autotaxin and serum bile acids are both possible pruritic mediators,” Emmanuel Gonzales, MD, PhD, of the Hôpital Bicêtre at the Universite Paris-Sud, said during his presentation at The Liver Meeting Digital Experience. “While some previous studies have shown a correlation between cholestatic pruritus and peripheral blood autotaxin levels on one hand, and serum bile acid levels on the other hand, other studies have not.”

Aimed to explore the relationship between odevixibat, an ileal bile acid transporter inhibitor, and PFIC parameters, researchers used pooled study data from phase 3 PEDFIC 1 and PEDFIC 2 studies. In PEDFIC 1, pediatric patients with PFIC received either placebo or odevixibat 40 g/kg daily or 120 g/kg daily for 24 weeks; PEDFIC 2 is the ongoing, 72week extension study among patients of any age with PFIC dosed with odevixibat 120 g/kg daily.

At the data cutoff date, the median exposure time to odevixibat was 37 weeks among 77 patients (mean age, 5.2 years; 51% girls); 88% continued with treatment. Compared with baseline, researchers observed decreases in ATX levels (–1,696 ng/mL), pruritus scores (–1.4) and serum bile acids (–49%) with a strong correlation between change from baseline in ATX with percent change in serum bile acids at week 25 to week 48. They further observed a moderate correlation between changes in baseline ATX and pruritus as well as between changes in pruritus and percent changes in serum bile acids.

“Odevixibat treatment reduced autotaxin, pruritus and serum bile acids in patients with PFIC. Significant correlations were observed between reductions in each pair of these three parameters,” Gonzales concluded. “ATX should be further investigated as a biomarker of cholestatic pruritis; a better understanding of the interplay between serum bile acids, autotaxin and cholestatic pruritis is still needed.”