EU/3/17/1851 - orphan designation for treatment of GM1 gangliosidosis

Adeno-associated viral vector serotype rh.10 expressing beta-galactosidase

Overview

On 20 March 2017, orphan designation (EU/3/17/1851) was granted by the European Commission to Lysogene, France, for adeno-associated viral vector serotype rh.10 expressing beta-galactosidase (also known as LYS-GM101) for the treatment of GM1 gangliosidosis.

What is GM1 gangliosidosis?

GM1 gangliosidosis is an inherited disorder that causes progressive damage to the nerve cells in the brain and spinal cord.

Patients with this condition lack an enzyme called beta-galactosidase which normally breaks down several molecules, including a substance called GM1 ganglioside. Without this enzyme, GM1 ganglioside builds up in the body, particularly in the brain and spinal cord, causing progressive nerve damage. Signs and symptoms include seizures (fits), learning disabilities, muscle weakness, skeletal abnormalities and problems walking and, as the disease progresses, enlargement of the heart, liver and spleen.

GM1 gangliosidosis is a debilitating and life-threatening disease. The most severe form of the disease starts in early infancy and can lead to death in a few years.

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

At the time of designation, GM1 gangliosidosis affected approximately 0.1 in 10,000 people in the European Union (EU). This was equivalent to a total of around 5,000 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).

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*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, no satisfactory methods were authorised in the EU to treat GM1 gangliosidosis. Treatment of patients was mainly supportive and included surgery and medicines to manage seizures, heart problems and infections.

How is this medicine expected to work?

The medicine is made of a virus that contains the gene for beta-galactosidase, the enzyme that is missing in patients with GM1 gangliosidosis. After the medicine is injected into the patient, the virus is expected to carry the gene into the cells, enabling them to produce the missing enzyme, thus restoring the body's ability to break down GM1 ganglioside.

The type of 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 GM1 gangliosidosis had been started.

At the time of submission, the medicine was not authorised anywhere in the EU for GM1 gangliosidosis. Orphan designation of the medicine had been granted in the United States 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/3/17/1851: Public summary of opinion on orphan designation: Adeno-associated viral vector serotype rh.10 expressing beta-galactosidase for the treatment of GM1 gangliosidosis

Adopted Reference Number: EMA/152998/2017

Key facts

• Active substance:
  Adeno-associated viral vector serotype rh.10 expressing beta-galactosidase
• Intended use:
  Treatment of GM1 gangliosidosis
• Orphan designation status:
  Positive
• EU designation number:
  EU/3/17/1851
• Date of designation:
  20/03/2017
• Sponsor:

  Lysogene; 18-20 rue Jacques Dulud; 92200 Neuilly-sur-Seine; France; 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.