On 27 July 2010, orphan designation (EU/3/10/753) was granted by the European Commission to Intercept Pharma, Italy, for 6alpha-ethyl-chenodeoxycholic acid (also known as obeticholic acid) for treatment of primary biliary cirrhosis.
The name of the sponsor was corrected to Intercept Italia S.R.L in May 2014.
6alpha-ethyl-chenodeoxycholic acid has been authorised in the EU as Ocaliva since 12 December 2016.
- What is primary biliary cirrhosis?
Primary biliary cirrhosis is a disease in which there is gradual destruction of the small bile ducts in the liver. These ducts transport a fluid called bile 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 pruritus (itching).
Primary biliary cirrhosis is ten times more common in women than in men. It 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 (an inability of the liver to work properly).
- What is the estimated number of patients affected by the condition?
At the time of designation, primary biliary cirrhosis affected not more than 3.9 in 10,000 people in the European Union (EU)*. This is equivalent to a total of not more than 182,000 people, and is below the threshold 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).
- What treatments are available?
At the time of designation, ursodeoxycholic acid was authorised in most EU countries for the treatment of primary biliary cirrhosis. Although this medicine can help to improve the flow of bile, about a third of patients with primary biliary cirrhosis do not respond to it. In advanced cases, the patient may need a liver transplant.
The sponsor has provided sufficient information to show that 6alpha-ethyl-chenodeoxycholic acid might be of significant benefit for patients with primary biliary cirrhosis because it might improve the treatment of patients with this condition, particularly patients who do not respond to the existing treatment. This assumption will need to be confirmed at the time of marketing authorisation, in order to maintain the orphan status.
- How is this medicine expected to work?
6alpha-ethyl-chenodeoxycholic acid is a natural bile acid that has been chemically modified to make it more active. It is expected to work mainly by activating the farnesoid X receptor (FXR), which controls the production of bile. By activating this receptor, this medicine is expected to reduce the production of bile in the liver, preventing it building up and damaging the liver tissue.
- What is the stage of development of this medicine?
The effects of 6alpha-ethyl-chenodeoxycholic acid have been evaluated in experimental models.
At the time of submission of the application for orphan designation, clinical trials with 6alpha-ethyl-chenodeoxycholic acid in patients with primary biliary cirrhosis were ongoing.
At the time of submission, 6alpha-ethyl-chenodeoxycholic acid was not authorised anywhere in the EU for primary biliary cirrhosis. Orphan designation of 6alpha-ethyl-chenodeoxycholic acid had been granted in the United States of America for primary biliary cirrhosis.
In accordance with Regulation (EC) No 141/2000 of 16 December 1999, the COMP adopted a positive opinion on 8 April 2010 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.
|Name||Language||First published||Last updated|
|EU/3/10/753: Public summary of opinion on orphan designation 6alpha-ethyl-chenodeoxycholic acid for treatment of primary biliary cirrhosis||(English only)||2010-08-05|
|Active substance||6alpha-ethyl-chenodeoxycholic acid|
|Disease/condition||Treatment of primary biliary cirrhosis|
|Date of decision||27/07/2010|
|Orphan decision number||EU/3/10/753|
Review of designation
On 14 October 2016, the Committee for Orphan Medicinal Products (COMP) completed its review of the designation EU/3/10/753 for Ocaliva (obeticholic acid1) as an orphan medicinal product for the treatment of primary biliary cirrhosis. The COMP assessed whether, at the time of marketing authorisation, the medicinal product still met the criteria for orphan designation. The Committee looked at the seriousness and prevalence of the condition, and the existence of other methods of treatment. As other methods of treatment are authorised in the European Union (EU), the COMP also considered whether the medicine is of significant benefit to patients with primary biliary cirrhosis. The COMP recommended that the orphan designation of the medicine be maintained2.
1Previously known as 6alpha-ethyl-chenodeoxycholic acid.
2The maintenance of the orphan designation at time of marketing authorisation would, except in specific situations, give an orphan medicinal product 10 years of market exclusivity in the EU. This means that in the 10 years after its authorisation similar products with the same therapeutic indication cannot be placed on the market.
- Life-threatening or long-term debilitating nature of the condition
The Committee for Medicinal Products for Human Use (CHMP) recommended the authorisation of Ocaliva for:
‘treatment of primary biliary cholangitis (also known as primary biliary cirrhosis) in combination with ursodeoxycholic acid (UDCA) in adults with an inadequate response to UDCA or as monotherapy in adults unable to tolerate UDCA’.
This falls within the scope of the product’s designated orphan indication, which is: ‘treatment of primary biliary cirrhosis’.
The COMP concluded that there had been no change in the seriousness of the condition since the orphan designation in 2010. Primary biliary cirrhosis remains a condition that is debilitating in the long-term and life-threatening because, when the disease progresses, it may lead to scarring and liver failure, and may increase the risk of liver cancer.
- Prevalence of the condition
The sponsor provided updated information on the prevalence of primary biliary cirrhosis based on data from the published literature.
On the basis of the information provided by the sponsor and the knowledge of the COMP, the COMP concluded that the prevalence of primary biliary cirrhosis remains below the ceiling for orphan designation, which is 5 people in 10,000. At the time of the review of the orphan designation, the prevalence was concluded to be 3.9 people in 10,000. This is equivalent to a total of around 200,000 people in the EU.
- Existence of other methods of treatment
At the time of the review of the orphan designation, ursodeoxycholic acid (UDCA) was authorised in the EU for the treatment of primary biliary cirrhosis.
- Significant benefit of Ocaliva
The COMP concluded that the claim of a significant benefit of Ocaliva in primary biliary cirrhosis is justified on the basis of the results of a clinical study in patients with the condition, which showed that Ocaliva can reduce the blood levels of bilirubin and ALP (markers of liver damage) in patients who do not respond adequately or cannot take UDCA. This is considered an indication of improvement of liver function.
Therefore, although other methods for the treatment of this condition have been authorised in the EU, the COMP concluded that Ocaliva is of significant benefit to patients affected by primary biliary cirrhosis.
Based on the data submitted and the scientific discussion within the COMP, the COMP considered that Ocaliva still meets the criteria for designation as an orphan medicinal product and that Ocaliva should remain in the Community Register of Orphan Medicinal Products.
Further information on the current regulatory status of Ocaliva can be found in the European public assessment report (EPAR) on the Agency’s website.
|Name||Language||First published||Last updated|
|Recommendation for maintenance of orphan designation at the time of marketing authorisation: Ocaliva (obeticholic acid) for the treatment of primary biliary cirrhosis||(English only)||2016-12-19|
Sponsor’s contact details
Intercept Italia S.R.L
c/o Studio Enrico Pellegrini
Via Settevalli 556
Tel. +39 075 7921 934
Fax +39 075 7921 934
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.