• Email
  • Help

Orphan designation

On 4 December 2007, orphan designation (EU/3/07/514) was granted by the European Commission to Genzyme Europe BV, Netherlands, for (1R,2R)-octanoic acid[2-(2',3'-dihydro-benzo[1,4] dioxin-6'-yl)-2-hydroxy-1-pyrrolidin-1-ylmethyl-ethyl]-amide-L-tartaric acid salt for the treatment of Gaucher disease.

What is Gaucher Disease?

Gaucher disease is characterized by the accumulation of specific chemical substances (glucocerebrosides) in several cells (macrophages and monocytes) that are localized throughout the body, but particularly in the spleen, liver and bone marrow. The disorder results from the decreased activity of an enzyme (a protein that stimulates a chemical reaction in the body), called glucocerebrosidase; this enzyme destroys the glucocerebrosides. Since glucocerebrosides are not destroyed, they progressively accumulate in the cells. The disorder has a genetic origin, so it is caused by damage in a gene that carries the information necessary for the production of the enzyme. Usually both parents are healthy carriers of a single copy of the damaged gene. To develop the disease, two damaged copies must be present in the same individual (this is called autosomal recessive inheritance). The severity of Gaucher disease is extremely variable; some patients show with virtually all the complications of Gaucher disease during childhood, while others remain asymptomatic for more than 70 years.

Gaucher disease has traditionally been divided into the following 3 clinical subtypes, according to the absence or presence of damage to the nerves and its progression:

  • Type 1 - Nonneuronopathic form (the most common and less severe form);
  • Type 2 - Acute neuronopathic form (the most severe form, usually diagnosed shortly after birth);
  • Type 3 - Chronic neuronopathic form (a form of intermediate severity between Type 1 and Type 2).

However, some cases do not precisely fit into one of these categories. Gaucher disease can be life-threatening (Type 2 and 3) or chronically debilitating (Type 1).

What are the methods of treatment available?

At the time of the application for orphan designation, two medicinal products were authorized in the European Union for the treatment of Gaucher syndrome, miglustat (Zavesca, given orally) and imiglucerase (Cerezyme, given intravenously). Given its different mechanism of action, (1R,2R)-octanoic acid[2-(2',3'-dihydro-benzo[1,4] dioxin-6'-yl)-2-hydroxy-1-pyrrolidin-1-ylmethyl-ethyl]-amide-L-tartaric acid salt may be of potential significant benefit over the currently authorised medicinal products. This assumption will have to be confirmed at the time of marketing authorisation, and this will be necessary to maintain the orphan status.

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

Based on the information provided by the sponsor and previous knowledge of the Committee, Gaucher disease was considered to affect 0.3 in 10,000 persons* in the European Union, which, at the time of designation, corresponded to about 15,000 persons.

*Disclaimer: For the purpose of the designation, the number of patients affected by the condition is estimated and assessed based on data from the European Union (EU 27), Norway, Iceland and Lichtenstein. This represents a population of 498,000,000 (Eurostat 2006). This estimate is based on available information and calculations presented by the sponsor at the time of the application.

How is this medicinal product expected to act?

(1R,2R)-Octanoic acid[2-(2’,3’-dihydro-benzo [1,4] dioxin-6’-yl)-2-hydroxy-1-pyrrolidin-1-ylmethyl-ethyl]-amide-L-tartaric acid salt blocks the function of an enzyme called glucosylceramide synthase. This enzyme helps to build the substance that accumulates in Gaucher disease (the glucocerebrosides, which then cannot be eliminated because of the genetic defect in the enzyme that destroys them). Thus, by blocking the action of glucosylceramide synthase, the levels of glucocerebrosides in the body are reduced and its accumulation should also be reduced.

What is the stage of development of this medicinal product?

The effects of the medicinal product were evaluated in experimental models.

At the time of submission of the application for orphan designation, clinical trials in patients with Gaucher disease were ongoing.

The medicinal product was not authorised anywhere in the world for Gaucher disease, or designated as orphan medicinal product elsewhere for this condition, at the time of submission.

According to Regulation (EC) No 141/2000 of 16 December 1999, the Committee for Orphan Medicinal Products (COMP) adopted on 10 October 2007 a positive opinion recommending the grant of the above-mentioned designation.

Opinions on orphan medicinal products designations are based on the following cumulative criteria:
  • the seriousness of the condition, 
  • the existence or not of alternative methods of diagnosis, prevention or treatment and 
  • either the rarity of the condition (considered to affect not more than five in ten thousand persons in the Community) or the insufficient return of development investments.

Designated orphan medicinal products are still investigational products which were considered for designation on the basis of potential activity. An orphan designation is not a marketing authorisation. As a consequence, demonstration of the quality, safety and efficacy will be necessary before this product can be granted a marketing authorisation.

Key facts

Product details for <p>(1R,2R)-octanoic acid[2-(2',3'-dihydro-benzo[1,4] dioxin-6'-yl)-2-hydroxy-1-pyrrolidin-1-ylmethyl-ethyl]-amide-L-tartaric acid salt</p>
Active substance(1R,2R)-octanoic acid[2-(2',3'-dihydro-benzo[1,4] dioxin-6'-yl)-2-hydroxy-1-pyrrolidin-1-ylmethyl-ethyl]-amide-L-tartaric acid salt
Medicine Name
Disease/conditionTreatment of Gaucher Disease
Date of decision03/12/2007
Orphan decision numberEU/3/07/514

Review of designation

During its meeting of 9 to 11 December 2014, the Committee for Orphan Medicinal Products (COMP) reviewed the designation EU/3/07/514 for Cerdelga (eliglustat)1 as an orphan medicinal product for the treatment of Gaucher disease. 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 Gaucher disease. The COMP recommended that the orphan designation of the medicine be maintained2.

1Previously known as (1R,2R)-octanoic acid[2-(2',3'-dihydro-benzo[1,4] dioxin-6'-yl)-2-hydroxy-1-pyrrolidin-1-ylmethyl-ethyl]-amide-L-tartaric acid salt.

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 a comparable 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 Cerdelga for:

‘Long-term treatment of adult patients with Gaucher disease type 1 (GD1), who are CYP2D6 poor metabolisers (PM), intermediate metabolisers (IMs) or extensive metabolisers (EMs)’.

This falls within the scope of the product’s designated orphan indication, which is: ‘Gaucher disease’.

The COMP concluded that there had been no change in the seriousness of the condition since the orphan designation in 2007. Gaucher disease remains a long-term debilitating and life-threatening condition that is associated with a reduced life expectancy if left untreated.

Prevalence of the condition

The sponsor provided updated information on the prevalence of Gaucher disease based on data from Orphanet (2013), the ICGG Gaucher registry and from the scientific literature. On the basis of the information provided by the sponsor and the knowledge of the COMP, the COMP concluded that the prevalence of Gaucher disease 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 still estimated to be approximately 0.3 people in 10,000. This is equivalent to a total of around 15,000 people in the EU.

Existence of other methods of treatment

At the time of the review of the orphan designation, three medicines, Cerezyme (imiglucerase), Vpriv (velaglucerase alfa) and Zavesca (miglustat), were authorised for the treatment of Gaucher disease in the EU. Cerezyme and Vpriv are ‘enzyme replacement therapies’ that work by replacing the missing enzyme. Zavesca is used as a second-line treatment in Gaucher disease patients who cannot receive enzyme replacement therapy.

Significant benefit of Cerdelga

The COMP concluded that the claim of a significant benefit of Cerdelga over enzyme replacement therapies is justified on the basis of its major contribution to patients’ care. This is because Cerdelga is to be taken by mouth, which is more convenient for patients with long-term disease than enzyme replacement therapies, which are given as a drip into a vein.

Comparing Cerdelga with Zavesca, the COMP noted that Zavesca can only be used in patients who cannot receive enzyme replacement therapy.

Therefore, although other methods for the treatment of this condition have been authorised in the EU, the COMP concluded that Cerdelga is of significant benefit to patients affected by Gaucher disease.


Based on the data submitted and the scientific discussion within the COMP, the COMP considered that Cerdelga still meets the criteria for designation as an orphan medicinal product and that it should remain in the Community Register of Orphan Medicinal Products.

Related information

Sponsor’s contact details

Genzyme Europe BV
Gooimeer 10
1411 DD Naarden
The Netherlands
Tel. +31 035 699 1452
Fax +31 035 699 1444

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.