James Squires, MD, University of Pittsburgh, discusses recent data regarding Bylvay (odevixibat) in patients with progressive familial intrahepatic cholestasis (PFIC) and Alagille syndrome.

 


PFIC is a heterogeneous group of autosomal recessive disorders of childhood that disrupt bile formation and present with cholestasis of hepatocellular origin.

Alagille syndrome is a rare genetic disease that affects the liver and other parts of the body. The liver problems result from having fewer small bile ducts than normal in the liver. This leads to bile building-up inside the liver, which in turn causes liver scarring and damage. Signs and symptoms of Alagille syndrome vary greatly but are generally noticed in infancy or early childhood. Alagille syndrome is caused by changes in the JAG1 and NOTCH2 genes.

Odevixibat is a once-daily non-systemic ileal bile acid transport (IBAT) inhibitor approved by the U.S. Food and Drug Administration (FDA) for the treatment of PFIC in patients three months of age and older with cholestatic pruritus. The drug is also approved for the treatment of cholestatic pruritus in patients 12 months of age and older with Alagille syndrome. 

Clinical Trial Data

Data was presented at the 2024 American Association for the Study of Liver Diseases (AASLD) pertaining to a phase 3 open-label extension PEDFIC 2 study in PFIC and the ASSERT-EXT long-term data in Alagille syndrome.

The PEDFIC 2 study demonstrated a clinically meaningful 1-point reduction in pruritus score at week 72 in 42% of patients younger than 18 years of age with PFIC 1 and 2 who transitioned to odevixibat at 24 weeks. The same was seen in 61% of patients of all ages and PFIC type. Rapid initial pruritus scores achieved by week 4 were sustained for patients remaining on treatment. At 72 weeks, serum bile acid levels were improved and increases were observed in patient height, weight, and sleep.

The ASSERT-EXT study demonstrated sustained improvements in pruritus and serum bile acid levels through week 72. At this point, 93% of patients receiving odevixibat throughout the 24 week ASSERT trial, and 77% of patients who transitioned from placebo to odevixibat at week 24 experienced clinically meaningful reductions of one point or greater in pruritus score. Additionally, increases to patient height, weight, and sleep were demonstrated.

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