Odevixibat 400microgram capsules

Progressive familiar intrahepatic cholestasis (PFIC) is a group of autosomal recessive disorders leading to cholestasis, fibrosis, and eventually a need for liver transplantation.[A236818] Patients with PFIC require liver transplants or develop hepatocellular carcinomas in their first few years of life.[A236818] Many of these patients experience severe pruritus.[A236818] The exact mechanism of pruritus is PFIC is not known, but lower concentrations of bile acids have been shown to reduce pruritus.[A236813][A236823][L34793] Patients with certain forms of PFIC type 2, associated with a non-functional or absent bile salt export pump, are not expected to benefit from odevixibat treatment.[L34793]

The ileal sodium/bile acid cotransporter is a transport glycoprotein responsible for reabsorption of 95% of bile acids in the distal ileum.[A236808] Odevixibat is a reversible inhibitor of the ileal sodium/bile acid contransporter.[A236808][L34793] Patients taking odevixibat for a week experienced a 56% reduction in bile acid area under the curve with a 3 mg once daily dose.[A236808] A 1.5 mg daily dose lead to a 43% reduction in bile acid area under the curve.[A236808]

The decreased reabsorption of bile acids, leads to reduced stimulation of FXR, which reduces expression of FGF19, reducing binding of FGF19 to FGF4R, decreasing inhibition of bile acid synthesis.[A236808] Further synthesis of bile acids that will not be reabsorbed in the intestine contributes to lowering low density lipoprotein levels.[A236808]