EU/3/16/1803: Orphan designation for the treatment of progressive myoclonic epilepsy type 2 (Lafora disease)

Lafora disease is an inherited brain disease marked by epileptic fits and worsening intellectual function. Patients usually have their first fit between 10 and 20 years of age. This is followed by worsening of the functioning of the brain and spinal cord, which causes severe epilepsy, difficulty walking, depression and dementia, and eventually leads to death. Lafora disease is caused by a fault in one of two genes called EPM2A or EPM2B.

Lafora disease is a debilitating and life-threatening disease that usually leads to death within 10 years of diagnosis.

At the time of designation, Lafora disease affected approximately 0.01 in 10,000 people in the European Union (EU). This was equivalent to a total of around 500 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 513,700,000 (Eurostat 2016).

At the time of designation, no satisfactory methods were authorised in the EU for treating Lafora disease. Medicines to control seizures were given, but their effectiveness was limited and did not last long, and they did not stop the disease from getting worse.

Metformin blocks production of glucose (a sugar) and has been used in the treatment of type 2 diabetes since the 1960s. The way it works in Lafora disease is not clear, however, it is thought to protect brain function possibly by increasing the action of an enzyme called AMP-activated protein kinase (AMPK). AMPK regulates the energy balance of cells including brain cells.

The effects of metformin have been evaluated in experimental models.

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

At the time of submission, metformin was not authorised anywhere in the EU for Lafora 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 4 November 2016 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.