Odevixibat Fails to Improve Native Liver Survival in Phase 3 BOLD Trial for Biliary Atresia

Ipsen announced on July 24, 2026, that the phase 3 BOLD trial evaluating odevixibat (Bylvay) in infants with biliary atresia who had undergone a Kasai hepatoportoenterostomy (HPE) did not meet its primary endpoint of improved native liver survival compared with placebo.1 The trial is the first global phase 3 study conducted in biliary atresia and enrolled 254 patients across 19 countries.1,2

“As the first global Phase III trial in biliary atresia, BOLD has generated the most comprehensive dataset ever assembled in this disease,” said Saul J. Karpen, MD, PhD, lead investigator and chief scientific officer at the Stravitz-Sanyal Institute for Liver Disease and Metabolic Health at Virginia Commonwealth University, in a press release.1 Karpen noted that further analysis of the dataset may still yield insight into whether outcomes differ across patient subgroups given the heterogeneity of the disease.1

BOLD Trial Design and Endpoints in Biliary Atresia

BOLD (NCT04336722) was a randomized, double-blind, placebo-controlled trial designed to test whether odevixibat could slow disease progression in infants who had already undergone Kasai HPE, the standard surgical intervention for biliary atresia performed in the first 90 days of life.1,2

Enrolled patients received oral odevixibat at 120 mcg/kg/day or placebo once daily for up to 104 weeks, with the primary endpoint defined as time from randomization to first occurrence of liver transplantation or death.1 According to the company, current topline data are consistent with odevixibat's previously established safety profile in its approved indications, though detailed safety and efficacy data from BOLD have not yet been published.1

An open-label extension study, BOLD-EXT (NCT05426733), is ongoing to evaluate longer-term safety and efficacy in patients who completed the parent trial; a decision on whether to continue patients in that extension will follow a full review of the BOLD dataset.1,3

Biliary Atresia Disease Burden and Treatment Gap

Biliary atresia is a rare, progressive pediatric cholestatic liver disease in which intrahepatic or extrahepatic bile ducts are blocked, absent, or scarred, leading to bile accumulation, inflammation, fibrosis, and eventual liver failure if untreated.1

It affects an estimated 1 in 5,000 to 20,000 newborns and is the leading cause of pediatric liver transplantation worldwide.1 While Kasai HPE can restore bile flow and delay progression when performed early, it is not curative, and many children still progress to transplant, typically before age 2.1

Until now, no pharmacologic therapy has been approved for biliary atresia beyond surgical management, leaving a substantial unmet need that prompted the design of BOLD as the largest disease-modification trial attempted in this population.1

Odevixibat Mechanism and Prior FDA Approvals

Odevixibat is a once-daily, nonsystemic ileal bile acid transporter (IBAT) inhibitor that reduces intestinal reabsorption of bile acids, promoting their fecal excretion.1

The FDA first approved odevixibat in July 2021 for pruritus in patients 3 months and older with progressive familial intrahepatic cholestasis (PFIC), based on a 24-week randomized trial in 62 pediatric patients, and the agency later expanded its indication to cholestatic pruritus in Alagille syndrome.4

What Comes Next for the BOLD Program

Ipsen has not yet released detailed efficacy or safety figures from BOLD, and the company indicates that subgroup and biology-focused analyses of the trial dataset are still forthcoming.1 Whether any signal emerges in specific patient subgroups, and how findings will inform continuation of BOLD-EXT participants, remain open questions pending Ipsen's comprehensive data review.1,3

References

1. IPSEN. Ipsen provides update on Phase III BOLD trial in biliary atresia. GlobalJuly 24, 2026. Accessed July 28, 2026. https://www.ipsen.com/press-release/ipsen-provides-update-on-phase-iii-bold-trial-in-biliary-atresia-3332691/

2. Efficacy and Safety of Odevixibat in Children With Biliary Atresia Who Have Undergone a Kasai HPE (BOLD). ClinicalTrials.gov identifier: NCT04336722. Updated 2026. https://clinicaltrials.gov/study/NCT04336722

3. An Open-label Extension Study to Evaluate Long-term Efficacy and Safety of Odevixibat in Children With Biliary Atresia (BOLD-EXT). ClinicalTrials.gov identifier: NCT05426733. Updated 2026. https://clinicaltrials.gov/study/NCT05426733

4. Food and Drug Administration approval summary: odevixibat (Bylvay) for the treatment of pruritus with progressive familial intrahepatic cholestasis. PMC. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12126724/