EU/3/10/807: Orphan designation for the treatment of frontotemporal dementia with parkinsonism-17

Frontotemporal dementia with parkinsonism-17 is a brain disorder with a wide range of symptoms that worsen over time. Patients may lose the ability to control or adjust their behaviour in different situations, leading to inappropriate behaviour. Language skills may also be affected, with the patient losing the ability to speak correctly, to pronounce words properly or to remember the right words. Patients may also show signs of Parkinson's disease such as shaking, slow movement and muscular stiffness.

The exact cause of the disease is unclear, but is thought to be related to the abnormal clumping together of proteins in the brain called 'tau', damaging different areas of the brain. The parts of the brain that are affected are the frontal and temporal (side) lobes.

Frontotemporal dementia with parkinsonism-17 is a debilitating disease that is life threatening because of its damaging effects on the brain.

At the time of designation, frontotemporal dementia with parkinsonism-17 affected approximately 0.03 in 10,000 people in the European Union (EU). This was equivalent to a total of around 2,000 people*, and is below the threshold 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 27), Norway, Iceland and Liechtenstein. At the time of designation, this represented a population of 506,300,000 (Eurostat 2010).

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

Methylthioninium is expected to work by dissolving the abnormal tangles of tau proteins in the brain of patients who have frontotemporal dementia with parkinsonism-17, thereby slowing down or reversing the symptoms of the disease.

The effects of methylthioninium have been evaluated in experimental models.
At the time of submission of the application for orphan designation, no clinical trials with methylthioninium in patients with frontotemporal dementia with parkinsonism-17 had been started.

At the time of submission, methylthioninium was used or authorised in several countries for the treatment of other diseases including urinary-tract infection, drug-induced methaemoglobinaemia, ifosfamide encephalopathy and refractory shock syndromes.

At the time of submission, methylthioninium was not authorised anywhere in the EU for frontotemporal dementia with parkinsonism-17 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 9 September 2010 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 European Union) 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.