Alagille Syndrome (ALGS)

Odevixibat is an experimental drug being developed by Albireo Pharma to treat rare pediatric cholestatic liver diseases including Alagille syndrome.1 The US Food and Drug Administration (FDA) granted it Orphan Drug Designation for the treatment of Alagille syndrome and other cholestatic diseases including biliary atresia and primary biliary cholangitis.2,3

The European Medicines Agency (EMA) also granted Orphan Drug Designation to odevixibat for the treatment of Alagille syndrome, biliary atresia, and primary biliary cholangitis. Moreover, the agency granted the treatment accelerated assessment and access to the priority medicines scheme for the treatment of progressive familial intrahepatic cholestasis.4

The FDA accepted Albireo’s New Drug Application for odevixibat for the treatment of pruritus in patients with progressive familial intrahepatic cholestasis in January 2021.5

Alagille Syndrome

In ALGS, mutations in the JAG1 or NOTCH2 genes impair the Notch signaling pathway, which plays an essential role in many developmental processes.6 This results in a wide range of symptoms affecting many organs and systems in the body. The hallmark of the disease is intrahepatic bile duct paucity, which leads to chronic cholestasis and pruritus. Bile duct paucity causes bile acids to accumulate inside the liver, causing liver damage. Up to a third of patients eventually develop serious liver disease and subsequent liver failure.8

There is currently no cure for ALGS, however, treatment options aim to reduce symptoms and increase patients’ quality of life. Experimental treatments like odevixibat are in clinical trials and aim to delay or stop the liver damage caused by the disease.

Molecular structure of odevixibat

Mechanism of Action

Odevixibat is a nonsystemic ileal bile acid transport inhibitor.

The ileum absorbs glyco-and taurine-conjugated forms of bile salts. The ileal bile acid transport is the first step in absorption at the brush-border membrane, and it plays a key role in the recirculation of bile acids secreted by the liver into the bile ducts back into the liver.4 Since there are fewer than normal bile ducts in ALGS, bile acids build up inside the liver to toxic levels, causing damage.

Odevixibat works by decreasing the reabsorption of bile acids from the small intestine to the liver.1 This could reduce the symptoms of ALGS such as pruritus and delay or prevent liver damage caused by toxic levels of bile acid accumulation.

Efficacy in Clinical Trials

The safety and efficacy of 2 doses of odevixibat have been tested in patients with progressive familial intrahepatic cholestasis types 1 and 2, aged 6 months to 18 years, in a phase 3 double-blind, randomized, placebo-controlled study.9 The results showed that odevixibat reduced serum bile acids and improved pruritus compared to the placebo.1

Interim results from an open-label phase 3 extension study showed continued and durable reductions in serum bile acids and improvements in pruritus. Odevixibat was generally well tolerated across both studies, and treatment-emergent adverse events were mostly mild or moderate. 

A phase 3 double-blind, randomized, placebo-controlled clinical trial called ASSERT is now assessing the safety and efficacy of odevixibat in the treatment of ALGS.10 The study is currently recruiting up to 63 participants of any age with ALGS in the US and France. 

Participants will either receive oral odevixibat or a placebo once a day for 24 weeks. The primary outcome measure will gauge the change in scratching score from baseline to month 6, as measured by the Albireo Observer-Reported Outcome scratching score. Secondary outcome measures will be the change in serum bile acid levels from baseline and the number of participants with treatment-emergent adverse events and serious adverse events. The trial started in March 2021 and is expected to run until July 2022.

Get prescribing information about odevixibat for other indications at MPR

Odevixibat is also being evaluated in a phase 3 study for the treatment of biliary atresia. The double-blind, randomized, placebo-controlled study will evaluate the safety and efficacy of the treatment in children up to 111 days old with biliary atresia who have undergone a Kasai hepatoportoenterostomy (HPE) at age less than or equal to 90 days. The study will also include those who are eligible to start study treatment within 3 weeks after a Kasai HPE.11 

The primary outcome measure of this study is the proportion of patients who are alive and have not undergone a liver transplant after 104 weeks of odevixibat treatment. Secondary outcome measures are the time to onset of any sentinel events, the time to pediatric end-stage liver disease, and total bilirubin and serum bile acid levels after 13, 26, 52, and 104 weeks of odevixibat treatment.

The study is recruiting up to 200 participants at 51 locations worldwide. Its estimated completion date is June 2024.


  1. Odevixibat. Albireo. Accessed June 18, 2021.
  2. Albireo granted Orphan Drug Designation for lead product candidate A4250 for treatment of Alagille syndrome. News release. Albireo; October 17, 2018. 
  3. Albireo has been granted Orphan Drug Designation for A4250 from the US FDA for the treatment of progressive familial intrahepatic cholestasis (PFIC) and for primary biliary cirrhosis (PBC). News release. Albireo; November 8, 2012.
  4. Inxight: drugs: odevixibat. National Center for Advancing Translational Sciences. Accessed June 18, 2021.
  5. Albireo announces U.S. FDA acceptance of new drug application for odevixibat. News release. Albireo; January 25, 2021. 
  6. Alagille syndrome. MedlinePlus. Updated April 7, 2021. Accessed June 18, 2021.
  7. Alagille syndrome. Johns Hopkins Medicine. Accessed June 18, 2021.
  8. Alagille syndrome | diagnosis & treatments. Boston Children’s Hospital. Accessed June 18, 2021.
  9. This study will investigate the efficacy and safety of A4250 in children with PFIC 1 or 2 (PEDFIC 1). June 25, 2018. Updated September 17, 2020. Accessed June 18, 2021.
  10. Efficacy and safety of odevixibat in patients with Alagille syndrome (ASSERT). December 19, 2020. Updated June 15, 2021. Accessed June 18, 2021.
  11. Efficacy and safety of odevixibat in children with biliary atresia who have undergone a Kasai HPE (BOLD). April 7, 2020. Updated June 4, 2021. Accessed June 18, 2021.

Reviewed by Debjyoti Talukdar, MD, on 7/1/2021.