EU/3/17/1949: Orphan designation for the treatment of GM2 gangliosidosis

GM2 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-hexosaminidase A, which normally breaks down a substance called GM2 ganglioside. Without this enzyme, GM2 ganglioside builds up in the body, particularly in the brain and spinal cord, causing progressive nerve damage. Signs and symptoms include muscle weakness and problems with walking, intellectual disability, difficulty speaking, seizures (fits), loss of sight and hearing.

GM2 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 during childhood.

At the time of designation, GM2 gangliosidosis affected less than 0.5 in 10,000 people in the European Union (EU). This was equivalent to a total of fewer than 26,000 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, no satisfactory methods were authorised in the EU to treat GM2 gangliosidosis. Treatment of patients was mainly supportive and included physical therapy and medicines to manage seizures.

Acetylleucine has been authorised in some countries for the treatment of vertigo (a spinning sensation that affects balance). The way acetylleucine works in GM2 gangliosidosis is not clear, but it is thought to stabilise the nerve cells responsible for balance and for coordinating movement. This is expected to improve movement control and coordination in patients with the disease.

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 GM2 gangliosidosis had been started.

At the time of submission, the medicine was not authorised anywhere in the EU for GM2 gangliosidosis 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.