EU/3/14/1310: Orphan designation for the treatment of Fabry disease

Fabry disease is an inherited disease that is caused by the lack of an enzyme called alpha-galactosidase A. This enzyme is contained in lysosomes (part of the body's cells that break down nutrients and other materials) where it breaks down and removes globotriaosylceramide (Gb3, a complex molecule of sugars and a fatty substance stored in the body). In patients who lack this enzyme, large amounts of Gb3 build up in tissues of vital organs, such as the kidneys and heart leading to kidney failure and heart problems. Gb3 also builds up in the tissues of the skin, eye and nervous system leading to lesions on the skin, clouding of the front part of the eye, pain in the hands and feet and neurological complications affecting the brain.

Fabry disease is a long-term debilitating disease due to recurrent episodes of severe pain not responding to analgesics. It is also life-threatening due to kidney, heart and brain complications.

At the time of designation, Fabry disease affected less than 2.3 in 10,000 people in the European Union (EU). This was equivalent to a total of fewer than 118,000 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 511,100,000 (Eurostat 2014).

At the time of designation, Fabrazyme (agalsidase beta) and Replagal (agalsidase alfa) were authorised in the EU to treat Fabry disease.

The sponsor has provided sufficient information to show that the medicine might be of significant benefit for patients with Fabry disease because early studies in experimental models suggest that it could improve the outcome of patients when used in combination with current therapies. This assumption will need to be confirmed at the time of marketing authorisation, in order to maintain the orphan status.

This medicine is expected to work by blocking the enzyme glucosylceramide synthase, which is involved in producing Gb3. By blocking the production of Gb3, the medicine is expected to slow down its build up in patients with Fabry disease, who lack alpha-galactosidase A and therefore cannot break Gb3 down. This is expected to lead to a reduction in Gb3, thereby reducing the symptoms of Fabry disease.

The effects of the medicine have been evaluated in experimental models.

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

At the time of submission, the medicine was not authorised anywhere in the EU for Fabry's disease 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 10 July 2014 recommending the granting of this designation.

• 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.