Odevixibat: an investigational inhibitor of the ileal bile acid transporter (IBAT) for the treatment of biliary atresia

ABSTRACT

Introduction

Biliary atresia (BA) is a rare, non-curable cholestasis-causing disease in infancy, due to progressive ascending bile duct sclerosis. Even after restoration of bile flow following Kasai portoenterostomy, about half of these children need a liver transplant by their 2nd birthday, due to progressive fibrosis. Toxicity of bile acids may play a central role in disease progression, but drug therapies are not yet available. With ileal bile acid transporter (IBAT) inhibitors, there is a potential novel drug option that inhibits the absorption of bile acids in the small intestine. As a result of reduced bile acid accumulation in the cholestatic liver, it may be possible to delay hepatic remodeling.

Areas covered

This review summarizes the dataset on bile acids and the potential effects of odevixibat, an IBAT inhibitor, in children with BA.

Expert opinion

Systemic reduction of bile acids with the aim of preventing inflammation, and thus liver remodeling, is a novel, promising, therapeutic concept. In principle, however, the time until diagnosis and surgical treatment of BA should still be kept as short as possible in order to minimize liver remodeling before medical intervention can be initiated. IBAT inhibitors may add to the medical options in limiting disease progression in BA.

KEYWORDS:

• Biliary atresia
• children
• bile acids
• ileal bile acid transporter
• IBAT
• odevixibat

Article highlights

• Biliary atresia is a non-curable, progressive, obliterative cholangiopathy in childhood and a leading cause for pediatric liver transplantation

• Accumulation of bile acids, due to cholestasis, promotes liver remodeling

• The use of IBAT inhibitors in cholestatic liver diseases, such as PFIC, yielded promising results in phase 3 studies, PEDFIC 1/PEDFIC 2, in the reduction of serum bile acids and pruritus

• The use of IBAT inhibitors in biliary atresia is currently under investigation in phase III trials to identify the true potential of this drug group

Declaration of interest

U Baumann has been a consultant to Albireo Pharma and Mirum Pharma. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This paper was not funded.