PARIS, France, July 24, 2026
Ipsen announced that its Phase III BOLD clinical trial evaluating Bylvay® (odevixibat) in patients with biliary atresia (BA) who previously underwent Kasai hepatoportoenterostomy (HPE) did not meet its primary endpoint of improving native liver survival compared with placebo. Although the study failed to demonstrate a statistically significant benefit in delaying liver transplantation or death, the topline safety findings remained consistent with the well-established safety profile of odevixibat observed in its approved indications. The outcome represents a setback for one of the first investigational medical therapies targeting biliary atresia, a rare and rapidly progressive pediatric liver disease that remains the leading cause of liver transplantation in children. Despite the disappointing efficacy results, investigators believe the trial has generated the largest and most comprehensive clinical dataset ever collected in biliary atresia, providing valuable scientific insights that may guide future research and treatment strategies..
Landmark Phase III Study Expands Understanding of a Rare Disease
The BOLD Phase III trial was a randomized, double-blind, placebo-controlled global study enrolling 254 infants across 19 countries who underwent Kasai HPE surgery within the first 90 days of life. Participants received either oral odevixibat 120 mcg/kg once daily or placebo for up to 104 weeks. The study’s primary endpoint measured native liver survival, defined as the time until liver transplantation or death. Although the primary objective was not achieved, clinical investigators emphasized the importance of the dataset generated through this international collaboration. Researchers noted that biliary atresia is a highly heterogeneous disease, with considerable differences in disease progression and patient outcomes, suggesting that additional subgroup analyses may identify patient populations that could benefit from future therapeutic approaches. The comprehensive findings are expected to contribute significantly to the scientific understanding of biliary atresia biology and disease progression.
Safety Profile Remains Consistent with Approved Indications
While efficacy goals were not met, Bylvay (odevixibat) continued to demonstrate a safety profile consistent with previous clinical experience in approved indications, including Progressive Familial Intrahepatic Cholestasis (PFIC) and Alagille Syndrome (ALGS). Odevixibat is a once-daily selective ileal bile acid transport (IBAT) inhibitor that reduces bile acid reabsorption in the intestine, lowering bile acid accumulation within the liver. The therapy is currently approved in the United States for the treatment of cholestatic pruritus in PFIC and pruritus associated with Alagille Syndrome, while in the European Union, it is approved for PFIC and marketed as KAYFANDA® for Alagille Syndrome. Ipsen stated that the BOLD-EXT open-label extension study remains ongoing while the company conducts a comprehensive review of the complete clinical dataset before determining whether enrolled patients will continue treatment under the extension protocol.
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Rare Pediatric Disease Continues to Present Major Unmet Need
Biliary atresia affects approximately one in every 5,000 to 20,000 newborns and is characterized by blocked or damaged bile ducts that prevent normal bile flow, resulting in progressive liver inflammation, fibrosis, cirrhosis, and ultimately liver failure if left untreated. Despite early Kasai surgery, many children eventually require liver transplantation, often before reaching two years of age. Currently, no approved medical therapies exist to slow disease progression beyond surgical intervention, highlighting the significant unmet medical need in this patient population. Although the BOLD trial did not deliver the desired efficacy outcome, Ipsen emphasized its continued commitment to advancing research in rare pediatric liver diseases. The knowledge generated from this landmark global study is expected to support future scientific discoveries, improve understanding of disease biology, and help shape the next generation of therapeutic development for children living with biliary atresia..
Source: Ipsen press release
