EU/3/16/1614

On 17 February 2016, orphan designation (EU/3/16/1614) was granted by the European Commission to RV Developpement, France, for tolfenamic acid for the treatment of behavioural variant frontotemporal dementia.

What is behavioural variant frontotemporal dementia?

Behavioural variant frontotemporal dementia is a brain disorder in which patients gradually lose their ability to control or adjust their behaviour in different situations, leading to inappropriate behaviour. Language skills may also be affected, with the patient not being able to speak correctly, to pronounce words properly or to remember the right words.

The exact cause of the disease is unclear, but it is thought to be related to the abnormal build-up and tangling of a protein in the brain called tau, which leads to damage in different areas of the brain. The parts of the brain that are affected are the frontal and temporal (side) lobes.

Behavioural variant frontotemporal dementia is a debilitating disease that is life threatening because of its damaging effects on the brain.

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

At the time of designation, behavioural variant frontotemporal dementia affected approximately 2.2 in 10,000 people in the European Union (EU). This was equivalent to a total of around 113,000 people*, and is below the ceiling for orphan designation, which is 5 people in 10,000. This isbased 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 513,700,000 (Eurostat 2016).

What treatments are available?

No satisfactory methods of treatment were authorised in the EU for behavioural variant frontotemporal dementia at the time of designation. Patients were supported in their day-to-day activities by caregivers with help from experts such as psychologists, physiotherapists and speech therapists.

How is this medicine expected to work?

Brain cells of patients with behavioural variant frontotemporal dementia produce excessive tau protein. In addition, the protein has extra phosphate groups attached to it which cause it to fold wrongly and become tangled. Tolfenamic acid interferes with Sp1, a factor that is essential for controlling the amount of tau protein that a cell makes, and the processes that add phosphate groups to the protein. This combined effect is expected to reduce the production of tau protein and the development of tangles, and thereby prevent cell damage and symptoms of behavioural variant frontotemporal dementia.

What is the stage of development of this medicine?

The effects of tolfenamic acid have been evaluated in experimental models.

At the time of submission of the application for orphan designation, no clinical trials with tolfenamic acid in patients with behavioural variant frontotemporal dementia had been started.

At the time of submission, tolfenamic acid was not authorised anywhere in the EU for behavioural variant frontotemporal dementia or designated as an orphan medicinal product elsewhere for this condition.

Tolfenamic acid has been authorised in Europe for many years as a non-steroidal anti-inflammatory medicine (NSAID) for the treatment of pain and inflammation.

In accordance with Regulation (EC) No 141/2000 of 16 December 1999, the COMP adopted a positive opinion on 21 January 2016 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.

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