Ipsen's Phase III BOLD Trial of Bylvay in Biliary Atresia Misses Primary Endpoint
Key Insights
Ipsen announced that the Phase III BOLD trial evaluating Bylvay (odevixibat) versus placebo in biliary atresia (search) patients post-Kasai hepatoportoenterostomy did not meet its primary endpoint of improved native liver survival.
The BOLD trial, the largest ever conducted in biliary atresia (search), enrolled 254 patients across 19 countries and generated the most comprehensive dataset assembled in this rare pediatric liver disease.
Biliary atresia (search) remains the leading cause of pediatric liver transplantation worldwide, with no approved pharmacological treatments currently available beyond surgery.
Ipsen announced on 24 July 2026 that the Phase III BOLD trial evaluating Bylvay (odevixibat) versus placebo in patients with biliary atresia (search) (BA) who have undergone a Kasai hepatoportoenterostomy (HPE) failed to meet its primary endpoint of improvement in native liver survival compared to placebo. The topline safety data were consistent with the well-established safety profile of odevixibat in its approved indications.
The BOLD trial represents the first global Phase III study ever conducted in biliary atresia (search) and the largest trial evaluating disease modification in this condition. The study enrolled 254 patients across 19 countries, all of whom had undergone Kasai HPE surgery within the first 90 days of life. Patients were randomized to receive either oral odevixibat at 120 mcg/kg/day or placebo once daily for up to 104 weeks. The primary endpoint was defined as time from randomization to first occurrence of liver transplant or death at week 104.
"This outcome is disappointing for patients living with this serious disease and their families," said Christelle Huguet, PhD, EVP Head of R&D at Ipsen. "These results reflect the significant challenge biliary atresia (search) presents as a complex, rare paediatric cholestatic liver disease which has so far evaded all therapeutic attempts beyond surgery."
A Disease with No Approved Pharmacological Treatments
Biliary atresia (search) is a rare, serious pediatric cholestatic liver disease affecting approximately 1 in 5,000 to 20,000 newborns. In this condition, the bile ducts inside or outside the liver become blocked, absent, or scarred, preventing bile from draining from the liver into the intestine. The resulting bile accumulation causes progressive inflammation, fibrosis, cirrhosis, and ultimately liver failure if left untreated. The condition typically manifests in newborns and young infants within the first weeks to months of life, often presenting with persistent jaundice, pale stools, and dark urine.
Biliary atresia (search) remains the most common cause of pediatric liver transplantation worldwide. While the Kasai HPE surgical procedure can restore bile flow and delay disease progression when performed early, it is not curative, and many patients ultimately require a liver transplant. Currently, there are no approved medical treatment options for BA beyond surgery.
The BOLD Trial: Landmark Dataset Despite Negative Outcome
Lead investigator Dr. Saul J. Karpen, MD PhD FAASLD, Pediatric Hepatologist and Chief Scientific Officer at the Stravitz-Sanyal Institute for Liver Disease and Metabolic Health at Virginia Commonwealth University, emphasized the broader significance of the trial despite its failure to meet the primary endpoint.
"Biliary atresia (search) is a rare and serious liver disease that affects babies. Progressing rapidly and with no effective medical treatments, many children develop severe liver damage and biliary atresia remains the number 1 cause of liver transplantation in children, often before the age of 2," said Dr. Karpen. "As the first global Phase III trial in biliary atresia, BOLD has generated the most comprehensive dataset ever assembled in this disease. Although the study did not meet its primary endpoint, the commitment of participating children and families has produced valuable insights that will deepen our understanding of biliary atresia and provide a crucial basis for future research and patient care."
Dr. Karpen further noted that biliary atresia (search) is a heterogeneous disease with variable clinical presentation and progression, and that further analyses of the comprehensive BOLD dataset may provide important insights into disease biology and help determine whether outcomes differ across patient subgroups.
Odevixibat's Mechanism and Approved Indications
Odevixibat is a once-daily, selective, and potent ileal bile acid transport (IBAT (search)) inhibitor that reduces bile acid reabsorption in the intestine. Through IBAT inhibition, bile acids are diverted and excreted with feces rather than being recirculated. Bylvay is currently approved in the United States as the first treatment for cholestatic pruritus in Progressive Familial Intrahepatic Cholestasis (PFIC) across all types, and for pruritus in patients with Alagille Syndrome (ALGS). In the European Union, Bylvay is approved for the treatment of PFIC with orphan exclusivity granted, and is additionally marketed as KAYFANDA for ALGS.
Next Steps and Ongoing Research
An open-label extension study, BOLD-EXT, is currently ongoing and evaluating the longer-term safety and efficacy of odevixibat in patients who have completed the BOLD trial. Ipsen stated that a decision regarding the continuation of patients in the open-label extension will be made following a comprehensive review of the full trial data.
Ipsen extended its gratitude to the patients, caregivers, investigators, and the broader biliary atresia (search) community for their dedication to the BOLD trial, acknowledging that their commitment has been instrumental in advancing the understanding of this challenging disease.