Ipsen's Phase III BOLD trial of Bylvay (odevixibat) in biliary atresia failed to meet its primary endpoint of improving native liver survival versus placebo, dealing a blow to the first late-stage effort to develop a drug for the rare pediatric liver disease.
Biliary atresia is the leading cause of pediatric liver transplantation worldwide. The current standard of care is Kasai hepatoportoenterostomy, but no drug has ever been approved for the disease.
Odevixibat is a once-daily ileal bile acid transporter (IBAT) inhibitor that blocks bile acid reabsorption in the small intestine, diverting bile acids for excretion in stool rather than allowing them to recirculate to the liver. The mechanism is already commercially established: Bylvay is approved in the US for cholestatic pruritus in progressive familial intrahepatic cholestasis (PFIC) and Alagille syndrome, and in the EU for PFIC, with a separate brand, Kayfanda, covering Alagille syndrome.
BOLD represented an attempt to extend that same bile-acid-diversion logic to a disease with a fundamentally different problem: not itch from bile acid accumulation, but progressive destruction of liver architecture following a partially effective surgical fix. The trial enrolled 254 infants across 19 countries who underwent Kasai surgery within 90 days of birth. Patients received once-daily odevixibat or placebo for up to 104 weeks. The primary endpoint was native liver survival, defined as time to liver transplantation or death. Ipsen did not disclose efficacy data, saying only that the study missed its primary endpoint. The safety profile was consistent with previous studies.