EU/3/19/2241: 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, which breaks down and removes Gb3, a molecule made up of sugars and fats.

In patients with this disease, 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 skin damage, clouding of the front part of the eye, pain in the hands and feet and complications affecting the brain.

Fabry disease is a long-term debilitating disease due to recurrent episodes of severe pain that cannot be relieved by painkillers. It is also life-threatening due to kidney, heart and brain complications.

At the time of designation, Fabry disease affected less than 2.6 in 10,000 people in the European Union (EU). This was equivalent to a total of fewer than 135,000 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 518,400,000 (Eurostat 2019).

At the time of designation, Fabrazyme (agalsidase beta), Galafold (migalastat) 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. Laboratory studies indicate that a single dose of the medicine could restore the activity of alpha-galactosidase A for a long time and thereby reduce the need for regular treatment. This assumption will need to be confirmed at the time of marketing authorisation, in order to maintain the orphan status.

This medicine is made of a virus that contains the gene for alpha galactosidase A, the enzyme that patients lack. When given by injection, the virus is expected to carry the gene into the patient’s liver cells, which would then start making the missing enzyme, thereby improving the symptoms of the disease.

The type of virus used in this medicine (adeno-associated virus) does not cause viral disease in humans. 

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

At the time of submission of the application for orphan designation, no clinical trials with the medicine in patients with Fabry disease had started.

At the time of submission, the medicine was not authorised anywhere in the EU for the treatment of Fabry disease or designated as an orphan medicinal product elsewhere for this condition.

In accordance with Regulation (EC) No 141/2000, the COMP adopted a positive opinion on 5 December 2019, 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.