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On 16 January 2014, orphan designation (EU/3/13/1215) was granted by the European Commission to Lumena Pharma UK Limited, United Kingdom, for (4R,5R)-1-[[4-[[4-[3,3-dibutyl-7-(dimethylamino)-2,3,4,5- tetrahydro-4-hydroxy-1,1-dioxido-1-benzothiepin-5-yl]phenoxy]methyl]phenyl]methyl]-4-aza-1-azoniabicyclo[2.2.2]octane chloride for the treatment primary biliary cirrhosis.
The sponsorship was transferred to Shire Pharmaceuticals Ireland Limited, Ireland, in September 2016 and subsequently to SFL Regulatory Services GmbH, Austria, in March 2019.
The sponsorship was transferred to Granzer Regulatory Consulting & Services, Germany in December 2019.
The sponsorship was transferred to Mirum Pharmaceuticals International B.V., Netherlands, in September 2021.
Please note that this product was withdrawn from the Union Register of orphan medicinal products in June 2022 on request of the Sponsor.
Primary biliary cirrhosis is a disease in which there is gradual destruction of the small bile ducts in the liver. These ducts transport fluid called bile from the liver towards the intestines, where it is used to help digest fats. As a result of the damage to the ducts, bile builds up in the liver and damages the liver tissue. Early symptoms of the disease include tiredness and itching. The disease is ten times more common in women than in men.
Primary biliary cirrhosis is a long-term debilitating and life-threatening disease because, when the disease progresses, it may lead to liver cirrhosis (scarring of the liver) and liver failure (inability of the liver to work properly), and may increase the risk of liver cancer.
At the time of designation, primary biliary cirrhosis affected approximately 3 in 10,000 people in the European Union (EU). This was equivalent to a total of approximately 154,000 people*, and is below the ceiling for orphan designation, which is 5 people in 10,000. This is based on the information provided by the sponsor and the knowledge of the Committee for Orphan Medicinal Products (COMP).
* Disclaimer: For the purpose of the designation, the number of patients affected by the condition is estimated and assessed on the basis of data from the European Union (EU 28), Norway, Iceland and Liechtenstein. This represents a population of 512,200,000 (Eurostat 2013).
At the time of designation, ursodeoxycholic acid was authorised in most EU countries for the treatment of primary biliary cirrhosis. In advanced cases, the patient may need a liver transplant.
The sponsor has provided sufficient information to show that this medicine might be of significant benefit for patients with primary biliary cirrhosis because experimental studies show its effectiveness in reducing excess bile acids and damage to the liver. These assumptions will need to be confirmed at the time of marketing authorisation, in order to maintain the orphan status.
The medicine is expected to reduce the amount of bile acid (a major component of bile) in the liver. It is expected to do so by interfering with the process by which most bile acids in the intestines are recovered and delivered back to the liver through the blood.
This medicine is thought to act locally on the intestines, blocking certain channels called ileal bile acid transporters through which the bile acids leave the intestine to reach the blood vessels that carry them back to the liver. By blocking these channels, the medicine is expected to help reduce the amount of bile acid in the liver, thereby reducing the liver damage and itching seen in patients with primary biliary cirrhosis.
At the time of submission of the application for orphan designation, the evaluation of the effects of the medicinal product in experimental models was ongoing.
At the time of submission, no clinical trials with the medicine in patients with primary biliary cirrhosis had been started.
At the time of submission, the medicine was not authorised anywhere in the EU for primary biliary cirrhosis or designated as an orphan medicinal product elsewhere for this condition.
In accordance with Regulation (EC) No 141/2000 of 16 December 1999, the COMP adopted a positive opinion on 6 November 2013 recommending the granting of this designation.
Designated orphan medicinal products are products that are still under investigation and are considered for orphan designation on the basis of potential activity. An orphan designation is not a marketing authorisation. As a consequence, demonstration of quality, safety and efficacy is necessary before a product can be granted a marketing authorisation.
Mirum Pharmaceuticals International B.V.
The Committee for Orphan Medicinal Products reviews the orphan designation of a product if it is approved for marketing authorisation.
This medicine is now known as maralixibat chloride.
EMA publishes information on orphan medicinal product designation adopted by the Committee for Orphan Medicinal Products (COMP) on the IRIS online platform:
For contact details of patients’ organisations whose activities are targeted at rare diseases, see:
European Organisation for Rare Diseases (EURORDIS), a non-governmental alliance of patient organisations and individuals active in the field of rare diseases.
Orphanet, a database containing information on rare diseases, which includes a directory of patients’ organisations registered in Europe.
The list of medicines that have received an orphan designation in the EU is available on the European Commission's website: