EU/3/17/1849 - orphan designation for treatment of Fabry disease

adeno-associated viral vector serotype 8 containing the human alpha-galactosidase A gene

Overview

On 20 March 2017, orphan designation (EU/3/17/1849) was granted by the European Commission to Freeline Therapeutics Ltd, United Kingdom, for adeno-associated viral vector serotype 8 containing the human alpha-galactosidase A gene for treatment of Fabry disease.

The sponsor's address was updated in July 2018.

The sponsorship was transferred to Freeline Therapeutics (Ireland) Limited Ireland in May 2019.

What is 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 analgesics. It is also life-threatening due to kidney, heart and brain complications.

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

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 134,000 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 515,700,000 (Eurostat 2017).

What treatments are available?

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 this medicine might be of significant benefit for patients with the condition. Laboratory studies indicate that a single dose of the medicine could restore 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.

How is this medicine expected to work?

This medicine is made up of a virus that contains the gene for alpha-galactosidase A, the enzyme the patient lacks. When given by injection, it is expected that the virus will carry the gene into the patient's liver cells, allowing the patient to start producing the missing enzyme and thereby relieve symptoms of the disease.

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

What is the stage of development of this medicine?

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 been started.

At the time of submission, the medicine 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 16 February 2017 recommending the granting of this 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;
• 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.

EU/3/17/1849: Public summary of opinion on orphan designation: Adeno-associated viral vector serotype 8 containing the human alpha-galactosidase A gene for treatment of Fabry disease

Adopted Reference Number: EMA/159926/2017

Key facts

• Active substance:
  adeno-associated viral vector serotype 8 containing the human alpha-galactosidase A gene
• Intended use:
  Treatment of Fabry disease
• Orphan designation status:
  Positive
• EU designation number:
  EU/3/17/1849
• Date of designation:
  20/03/2017
• Sponsor:

  Freeline Therapeutics (Ireland) Limited; 6th Floor, 2 Grand Canal Square; Dublin 2; Ireland; Tel: [phone]; E-mail: [e-mail]

Review of designation

The Committee for Orphan Medicinal Products reviews the orphan designation of a product if it is approved for marketing authorisation.