Ipsen (Euronext: IPN; ADR: IPSEY) reported on July 24 that the Phase III BOLD trial of odevixibat (Bylvay) in biliary atresia failed to meet its primary endpoint, closing off what had been the only late-stage pharmacological attempt to improve native liver survival in a disease that remains entirely dependent on surgery.
The BOLD trial enrolled 254 pediatric patients across 19 countries who had undergone Kasai hepatoportoenterostomy within the first 90 days of life. Patients received oral odevixibat 120 mcg/kg/day or placebo once daily for up to 104 weeks. The primary endpoint — native liver survival, defined as time to liver transplant or death through week 104 — was not met. Topline safety data were described as consistent with odevixibat's established profile in approved indications.
Odevixibat is a minimally systemic inhibitor of the ileal bile acid transporter (IBAT), blocking reabsorption of bile acids in the terminal ileum and reducing their enterohepatic recirculation. The drug is approved in the US as the first treatment for cholestatic pruritus in progressive familial intrahepatic cholestasis across all types, and for pruritus in Alagille syndrome; in the EU it is approved for PFIC and marketed as Kayfanda for Alagille syndrome.
The failure is biologically informative. Biliary atresia involves obstruction or absence of the bile ducts, which prevents bile from reaching the intestine altogether in many patients — precisely the setting where a gut-restricted IBAT inhibitor faces a fundamental mechanistic limitation. If bile acids are not reaching the ileum in sufficient quantities, blocking their reabsorption there may produce little therapeutic effect on hepatic bile acid accumulation or fibrosis progression. Ipsen acknowledged the disease's heterogeneity and said subgroup analyses of the full dataset may yield insights into whether outcomes differed across patient populations.
The trial was the first global Phase III study ever conducted in biliary atresia and generated what Ipsen described as the largest clinical dataset assembled in the disease. An open-label extension, BOLD-EXT, is currently ongoing; Ipsen said continuation decisions for enrolled patients will follow a comprehensive review of the full data.