EU/3/17/1953: 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 complex molecule containing sugars and fats.

In patients with this condition, 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 complications affecting the brain.

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

At the time of designation, Fabry disease affected approximately 2.2 in 10,000 people in the European Union (EU). This was equivalent to a total of around 113,000 people¹, 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).

¹Disclaimer: 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 515,700,000 (Eurostat 2017).

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 pegunigalsidase alfa might be of significant benefit for patients with Fabry disease. Data from preliminary studies showed that the medicine reduces nerve damage in the hands and feet, and may be less likely than authorised treatments to trigger the production of antibodies which can prevent the medicine from working effectively. In addition the medicine is expected to be used in a wider population than migalastat. These assumptions will need to be confirmed at the time of marketing authorisation, in order to maintain the orphan status.

Pegunigalsidase alfa is expected to work as an enzyme replacement therapy. It is expected to replace the human enzyme alpha galactosidase A, which people with Fabry disease are lacking, helping to break down Gb3 and stop it from building up in the patient's tissues.

Pegunigalsidase alfa is produced by a method known as 'recombinant DNA technology': it is made by cells into which a gene (DNA) has been introduced, which makes them able to produce the enzyme. The replacement enzyme has also been modified to reduce the rate at which it is removed from the body, allowing it to act for longer.

The effects of pegunigalsidase alfa have been evaluated in experimental models.

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

At the time of submission, pegunigalsidase alfa was not authorised anywhere in the EU for Fabry 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 31 October 2017 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.