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Orphan designation

On 17 July 2012, orphan designation (EU/3/12/1028) was granted by the European Commission to Albireo AB, Sweden, for (2S)-2-{[(2R)-2-[({[3,3-dibutyl-7-(methylthio)-1,1-dioxido-5-phenyl-2,3,4,5-tetrahydro-1,2,5-benzothiadiazepin-8-yl]oxy}acetyl)amino]-2-(4-hydroxyphenyl)acetyl]amino}butanoic acid for the treatment of progressive familial intrahepatic cholestasis.

What is progressive familial intrahepatic cholestasis?

Progressive familial intrahepatic cholestasis is an inherited condition that causes progressive liver disease, which normally leads to liver failure. In progressive familial intrahepatic cholestasis, a fluid produced by the liver called bile, which helps digestion, is not ‘transported’ normally to the intestine. This results in bile acids, essential components of bile, building up in liver cells and becoming toxic to the liver and causing cirrhosis (scarring). Symptoms usually begin in infancy and include severe itching, jaundice (yellowing of the skin and eyes), delayed growth, pancreatitis (inflammation of the pancreas) and bleeding inside the stomach or the gut. At later stages, high blood pressure in the vein that supplies blood to the liver and liver failure will appear.

Progressive familial intrahepatic cholestasis is chronically debilitating due to early appearance of the symptoms and liver problems. It is also life-threatening due to severe liver damage.

What is the estimated number of patients affected by the condition?

At the time of designation, progressive familial intrahepatic cholestasis affected not more than 0.2 in 10,000 people in the European Union (EU)*. This is equivalent to not more than 10,000 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 27), Norway, Iceland and Liechtenstein. This represents a population of 506,300,000 (Eurostat 2011).

What treatments are available?

At the time of orphan designation, no satisfactory treatments were authorised in the EU for this condition. Rifampicin was used to treat the itchiness, ursodeoxycholic acid was used to treat some types of progressive familial intrahepatic cholestasis and vitamin supplements were given to children to prevent deficiencies. Patient with end-stage liver disease underwent liver transplantation.

How is this medicine expected to work?

The medicine is expected to block some proteins on the surface of intestinal cells called ‘ileal sodium-dependent bile-acid transporters’. These bile acid transporters are involved in the transport of bile acids from the intestines back to the liver, where they are recycled to produce more bile, a process known as ‘bile-acid re-uptake’. By blocking the transporters, the medicine is expected to reduce the entry of bile acids into liver cells, and thereby prevent their accumulation and the toxicity in the liver cells. This is expected to help improve the symptoms of the disease.

What is the stage of development of this medicine?

At the time of submission of the application for orphan designation, the evaluation of the effects of the medicine in experimental models was ongoing.

At the time of submission, no clinical trials with the medicine in patients with progressive familial intrahepatic cholestasis had been started.

At the time of submission, the medicine was not authorised anywhere in the EU for progressive familial intrahepatic cholestasis 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 13 June 2012 recommending the granting of this designation.

Opinions on orphan medicinal product designations are based on the following three criteria:
  • the seriousness of the condition;
  • the existence of alternative methods of diagnosis, prevention or treatment;
  • either the rarity of the condition (affecting not more than 5 in 10,000 people in the EU) or insufficient returns on investment.

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.

Key facts

Product details for <p>(2S)-2-{[(2R)-2-[({[3,3-dibutyl-7-(methylthio)-1,1-dioxido-5-phenyl-2,3,4,5-tetrahydro-1,2,5-benzothiadiazepin-8-yl]oxy}acetyl)amino]-2-(4-hydroxyphenyl)acetyl]amino}butanoic acid</p>
Active substance(2S)-2-{[(2R)-2-[({[3,3-dibutyl-7-(methylthio)-1,1-dioxido-5-phenyl-2,3,4,5-tetrahydro-1,2,5-benzothiadiazepin-8-yl]oxy}acetyl)amino]-2-(4-hydroxyphenyl)acetyl]amino}butanoic acid
Medicine Name
Disease/conditionTreatment of progressive familial intrahepatic cholestasis
Date of decision17/07/2012
Orphan decision numberEU/3/12/1028

Review of designation

The Committee for Orphan Medicinal Products reviews the orphan designation of a product if it is approved for marketing authorisation.

Sponsor’s contact details

Albireo AB
Arvid Wallgrens Backe 20
S-413 46 Gothenburg
Tel. +46 31 741 14 80
Fax +46 31 82 02 23

Patients' organisations

For contact details of patients’ organisations whose activities are targeted at rare diseases, see:

  • Orphanet, a database containing information on rare diseases which includes a directory of patients’ organisations registered in Europe.
  • European Organisation for Rare Diseases (EURORDIS), a non-governmental alliance of patient organisations and individuals active in the field of rare diseases.