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Odevixibat

Odevixibat, also known as A4250, is an investigational drug being studied in clinical trials for the treatment of several rare liver disorders affecting children. These disorders include Progressive Familial Intrahepatic Cholestasis (PFIC), Alagille Syndrome (ALGS), and Biliary Atresia (BA). Odevixibat works by inhibiting a protein called the ileal bile acid transporter (IBAT), which may help reduce bile acid buildup and relieve symptoms like severe itching. This article summarizes key information from recent clinical trials evaluating odevixibat’s safety and effectiveness in pediatric patients with these challenging liver conditions.

Table of Contents

What is Odevixibat?

Odevixibat, also known by its research name A4250, is a new medication designed to treat rare liver diseases in children[1]. It was authorized by the United States Food and Drug Administration on June 13, 2023, for treating cholestatic pruritus (severe itching caused by liver problems) in infants with Alagille Syndrome who are over 12 months old[1].

How Does Odevixibat Work?

Odevixibat is a small molecule and selective inhibitor of IBAT (Ileal Bile Acid Transporter)[1]. This means it works by blocking a specific protein in the intestines that normally helps to recycle bile acids. By doing this, Odevixibat helps to reduce the amount of bile acids in the body, which can help alleviate symptoms associated with certain liver diseases[4].

What Conditions Does Odevixibat Treat?

Odevixibat is being studied for several rare liver conditions in children, including:

  • Alagille Syndrome (ALGS): A genetic disorder that can affect multiple organ systems, including the liver, heart, skeleton, eyes, and kidneys. It often causes blockage of bile flow from the liver, yellowing of the skin (jaundice), poor growth, and severe itching[1].
  • Progressive Familial Intrahepatic Cholestasis (PFIC): A group of rare genetic disorders that affect the liver and can lead to liver failure[3].
  • Biliary Atresia: A condition in infants where the bile ducts outside and inside the liver are scarred and blocked[2].

Clinical Trials and Research

Odevixibat is currently being studied in several clinical trials:

  • ASSERT study: A Phase 3 trial for patients with Alagille Syndrome[4].
  • BOLD study: A Phase 3 trial for children with Biliary Atresia who have undergone a Kasai procedure (a type of surgery for this condition)[5].
  • PEDFIC 1 and PEDFIC 2 studies: Phase 3 trials for children with PFIC types 1 and 2[6][7].

How is Odevixibat Administered?

Odevixibat is given as capsules for oral administration, usually once daily. The dose is typically based on the child’s weight. In most studies, doses of 40 μg/kg/day or 120 μg/kg/day are being tested[7].

Effectiveness of Odevixibat

The effectiveness of Odevixibat is being measured in several ways:

  • Reduction in itching (pruritus): This is often measured using special tools like the Albireo Observer-Reported Outcome (ObsRO) instrument, where caregivers report on the child’s scratching behavior[4].
  • Reduction in serum bile acids: This measures the amount of bile acids in the blood[4].
  • Improved growth: Some studies are looking at whether Odevixibat can help improve children’s growth[6].
  • Liver health: Researchers are examining various markers of liver health and function[2].
  • Quality of life: Some studies are assessing whether Odevixibat improves overall quality of life for patients[1].

Safety and Side Effects

The safety of Odevixibat is being closely monitored in all clinical trials. Researchers are tracking any adverse events (side effects) that occur during treatment. So far, the specific side effects have not been detailed in the provided information, but this is a crucial aspect of the ongoing research[4].

Future Prospects

Odevixibat shows promise in treating several rare liver diseases in children. If the ongoing clinical trials continue to show positive results, it could become an important treatment option for conditions that currently have limited therapeutic choices. Some studies are also looking at the long-term effects of Odevixibat, which will provide valuable information about its use over extended periods[1][2].

Aspect Details
Drug Name Odevixibat (also known as A4250)
Mechanism of Action Selective inhibitor of the ileal bile acid transporter (IBAT)
Conditions Studied Progressive Familial Intrahepatic Cholestasis (PFIC), Alagille Syndrome (ALGS), Biliary Atresia (BA)
Administration Oral capsules, once daily
Dosage Range 40-120 μg/kg/day in most trials
Primary Outcomes Reduction in pruritus (itching), decrease in serum bile acids, improved liver function
Secondary Outcomes Growth parameters, quality of life, delay/prevention of liver transplant
Trial Durations 24-104 weeks, with some having optional extension periods
Safety Monitoring Adverse events, physical exams, laboratory tests, growth measurements

FAQ

  • What is odevixibat and how does it work? Odevixibat (also called A4250) is an experimental drug that inhibits a protein called the ileal bile acid transporter (IBAT). By blocking IBAT, odevixibat may help reduce the buildup of bile acids in the liver and blood, which can cause severe itching and liver damage in certain rare disorders.
  • What conditions is odevixibat being studied to treat? Odevixibat is being evaluated in clinical trials for several rare pediatric liver disorders, including Progressive Familial Intrahepatic Cholestasis (PFIC), Alagille Syndrome (ALGS), and Biliary Atresia (BA). These conditions can cause cholestasis, which is a reduction or blockage of bile flow from the liver.
  • How is odevixibat administered in the clinical trials? In the clinical trials, odevixibat is given as oral capsules taken once daily. The dosage varies between studies but is typically in the range of 40-120 micrograms per kilogram of body weight per day.
  • What are some of the main outcomes being measured in the odevixibat trials? Key outcomes being evaluated include changes in itching/scratching severity, serum bile acid levels, liver function tests, growth parameters, and quality of life measures. The trials are also assessing the long-term safety of odevixibat and its effects on delaying or preventing the need for liver transplantation.
  • How long do the odevixibat clinical trials typically last? The duration of the trials varies, but many include a treatment period of 24-104 weeks (about 6 months to 2 years), with some having optional extension periods to allow for longer-term treatment and follow-up. This allows researchers to evaluate both the short-term and long-term effects of odevixibat.

Ongoing Clinical Trials on Odevixibat

  • Study on Long-term Effects and Safety of Odevixibat in Children with Biliary Atresia

    Recruiting

    1 1 1
    Investigated drugs:
    Belgium France Germany Hungary Italy The Netherlands +2

  • Long-term Study on the Safety and Effectiveness of Odevixibat for Patients with Alagille Syndrome

    Not recruiting

    1 1 1 1
    Investigated diseases:
    Investigated drugs:
    Belgium France Germany Italy The Netherlands Poland

Glossary

  • Alagille Syndrome (ALGS): A rare genetic disorder that can affect multiple organ systems of the body including the liver, heart, skeleton, eyes and kidneys. It often causes cholestasis (reduced bile flow) in infants.
  • Biliary Atresia (BA): A rare condition in infants where the bile ducts outside and inside the liver are scarred and blocked. This prevents bile from flowing into the intestine, leading to liver damage.
  • Cholestasis: A condition where the flow of bile from the liver is reduced or blocked. This can lead to a buildup of bile acids in the liver and blood, causing itching and other symptoms.
  • Ileal Bile Acid Transporter (IBAT): A protein in the intestines that helps recycle bile acids back to the liver. Odevixibat works by inhibiting this transporter.
  • Kasai Hepatoportoenterostomy: A surgical procedure performed on infants with biliary atresia to restore bile flow from the liver to the intestine.
  • Progressive Familial Intrahepatic Cholestasis (PFIC): A group of rare genetic disorders that cause progressive liver disease and typically appear in infancy or early childhood.
  • Pruritus: Severe itching, which is a common and distressing symptom in many liver disorders affecting children.
  • Serum Bile Acids: The level of bile acids in the blood, which can be elevated in liver diseases and is often used as a marker of liver function and bile flow.

References

  1. https://clinicaltrials.gov/study/NCT05035030
  2. https://clinicaltrials.gov/study/NCT05426733
  3. https://clinicaltrials.gov/study/NCT04483531
  4. https://clinicaltrials.gov/study/NCT04674761
  5. https://clinicaltrials.gov/study/NCT04336722
  6. https://clinicaltrials.gov/study/NCT03659916
  7. https://clinicaltrials.gov/study/NCT03566238