On 22 May 2006, orphan designation (EU/3/06/368) was granted by the European Commission to Amicus Therapeutics UK Limited, United Kingdom, for 1-deoxygalactonojirimycin hydrochloride for the treatment of Fabry disease.
The sponsorship was transferred to Shire Pharmaceutical Development Limited, United Kingdom, in June 2008, to Amicus Therapeutics UK Ltd, United Kingdom, in February 2010 and subsequently to Glaxo Group Limited, United Kingdom, in June 2011.
- What is Fabry disease?
Fabry disease comprises a group of inherited lysosomal storage disorders. Lysosomes are small vesicles within cells containing enzymes that are able to destroy or transform different substances of the cell, such as proteins, fat, nucleic acids (components of the genetic material) and sugars. Any change of the lysosomal enzymes causes abnormal accumulation of the substance (also known as substrate) normally transformed by it. Cells are unable to destroy or eliminate accumulated substrates, and high levels of them can be toxic leading to damage and malfunction of the organ where accumulation occurs. In Fabry disease, the activity of the lysosomal enzyme α-galactosidase A is impaired or absent. Fabry disease is a heterogenous disorder with variable onset of symptoms that affect several organs. Glycosphingolipids (biological molecules composed of a type of sugar and lipid) is the substrate that accumulates in Fabry disease, and severity of the disease depends on the level of accumulation. Fabry disease affects the nervous system, kidneys, heart, skin and gastrointestinal system. Some of the most common pathological symptoms are skin lesions and burning pain of the extremities. This pain can become very intense, especially when one has a fever. Fabry disease is chronically debilitating and life threatening.
- What is the estimated number of patients affected by the condition*?
At the time of designation Fabry disease affected approximately 1 in 10,000 people in the European Union (EU)*. This is based on the information provided by the sponsor and knowledge of the Committee for Orphan Medicinal Products (COMP). This is below the threshold for orphan designation which is 5 in 10,000. This is equivalent to a total of around 46,000 people.
* 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 25), Norway, Iceland and Liechtenstein. This represents a population of 459,700,000 (Eurostat 2004).
- What treatments are available?
Several products were authorised for the condition in the Community at the time of submission of the application for orphan drug designation. In particular, enzymes replacing the missing enzyme were used to treat Fabry disease.
1-deoxygalactonojirimycin hydrochloride might be of potential significant benefit for the treatment of Fabry disease, as it may act in a different way which is hoped to improve the long-term outcome of the patients. This assumption will have to be confirmed at the time of marketing authorisation. This will be necessary to maintain the orphan status.
- How is this medicine expected to work?
1-deoxygalactonojirimycin hydrochloride is expected to bind to the abnormal α-galactosidase A enzyme and to correct its transport into the lysosome where its action is needed. This way, it is expected that the α-galactosidase A activity is restored. The abnormally high levels of glycosphingolipids are decreased and the extent of Fabry disease and its clinical consequences are limited.
- What is the stage of development of this medicine?
The effects of 1-deoxygalactonojirimycin hydrochloride were evaluated in experimental models.
At the time of submission of the application for orphan designation, clinical trials in patients with Fabry disease were ongoing.
1-deoxygalactonojirimycin hydrochloride was not authorised anywhere worldwide for Fabry disease, at the time of submission. Orphan designation of 1-deoxygalactonojirimycin hydrochloride was granted in the United States for treatment of Fabry disease.
According to Regulation (EC) No 141/2000 of 16 December 1999, the Committee for Orphan Medicinal Products (COMP) adopted on 5 April 2006 a positive opinion recommending the grant of the above-mentioned 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;
- and either the rarity of the condition (affecting not more than five in 10,000 people in the Community) or the 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 the quality, safety and efficacy is necessary before a product can be granted a marketing authorisation.
|Name||Language||First published||Last updated|
|EU/3/06/368: Public summary of positive opinion for orphan designation of 1-deoxygalactonojirimycin hydrochloride for the treatment of Fabry disease||(English only)||15/05/2009||05/09/2011|
|Active substance||1-Deoxygalactonojirimycin hydrochloride|
|Disease/condition||Treatment of Fabry disease|
|Date of decision||22/05/2006|
|Orphan decision number||EU/3/06/368|
Review of designation
Sponsor’s contact details
Glaxo Group Limited
Glaxo Wellcome House
Middlesex UB6 0NN
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.