Odevixibat for treating progressive familial intrahepatic cholestasis

Progressive familial intrahepatic cholestasis (PFIC) is the name given to a group of genetic disorders that affect the liver. They result in the flow of bile from the liver to the gastrointestinal tract being reduced or stopping completely. This causes bile to accumulate in the liver cells (cholestasis), which start to die and are replaced with scar tissue. This leads to cirrhosis (severe scarring) and liver failure. PFIC is caused by mutations in the genes that encode the proteins involved in transporting bile out of the liver, adversely affecting their function. Three main types have been identified. The most prevalent, PFIC2, is caused by mutations in the ABCB11 gene. PFIC1 is caused by mutations in the ATP8B1 gene, and PFIC3 by mutations in the ABCB4 gene. Rarer types, such as PFIC4, PFIC5 and PFIC6, have been identified. PFIC is typically inherited in an autosomal recessive pattern, meaning that 2 copies of the mutated gene (1 from each parent) must be present for it to develop. In PFIC1 and PFIC2, symptoms usually occur in the first months of life. PFIC3 can also appear later in infancy, in childhood or even during young adulthood. PFIC progresses at varying rates dependent on the type, but usually develops into cirrhosis within the first decade of life. It is fatal if untreated.

People with PFIC have a wide range of symptoms, determined primarily by the type they have. However, in all types, the condition is characterised by severe pruritus (itching), jaundice and raised serum bile acid levels. Diagnosis is primarily clinical. Other symptoms occurring outside the liver include diarrhoea, fat-soluble vitamin deficiencies and poor growth. These are more common in PFIC1. PFIC2 in particular is characterised by more rapid disease progression and a higher risk of liver cancer.

The prevalence of PFIC in England is unknown. However, worldwide estimates range between 1 per 50,000 to 1 per 100,000 live births. The marketing authorisation for odevixibat covers all types of PFIC.

There are no licensed medicines for PFIC. Initial management includes off-label medicines (for example, ursodeoxycholic acid, rifampicin, cholestyramine). The aim with these is to control the cholestatic pruritus. They are often given in combination and used alongside nutritional management, such as vitamin supplements to optimise nutrient absorption and promote growth. Surgical options are used when pruritus persists despite these off-label medicines. It includes surgical biliary diversion (SBD) and a liver transplant. Partial external biliary diversion is the most common form of SBD and involves diverting bile away from the gallbladder via an external stoma. A liver transplant is needed by most people with PFIC.