EU/3/15/1446

On 12 February 2015, orphan designation (EU/3/15/1446) was granted by the European Commission to AlzProtect S.A.S., France, for N-(3-(4-(3-(diisobutylamino)propyl)piperazin-1-yl)propyl)-1H-benzo[d]imidazol-2-amine disulphate salt (also known as AZP2006) for the treatment of progressive supranuclear palsy.

What is progressive supranuclear palsy?

Progressive supranuclear palsy, which is also known as Steele-Richardson-Olszewski syndrome, is a rare disease that involves the gradual deterioration of brain cells. Symptoms include loss of balance with unexplained falls, stiffness, difficulty moving the eyes, particularly up and down, personality changes and dementia (loss of intellectual function). The disease usually starts in people aged over 60 years and gradually gets worse over a number of years.

Patients with progressive supranuclear palsy have abnormal tangles of a protein called ‘tau’ in their brain, which are thought to cause the gradual deterioration of brain tissue seen in these patients.

Progressive supranuclear palsy is a debilitating and life-threatening disease that leads to parkinsonism, paralysis and premature death.

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

At the time of designation, progressive supranuclear palsy affected approximately 1.4 in 10,000 people in the European Union (EU). This was equivalent to a total of around 72,000 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 512,900,000 (Eurostat 2015).

What treatments are available?

At the time of designation, no satisfactory methods were authorised in the EU for the treatment of progressive supranuclear palsy. Because of their tendency to fall, patients were often offered walking aids, as well as special glasses to help them to look down. Physiotherapy was used to keep the joints flexible. For patients unable to swallow, a feeding tube leading through the tummy to the stomach was used. Medicines developed to treat Parkinson’s disease were also used in some patients, but their effect was usually limited, and did not last long.

How is this medicine expected to work?

In patients with progressive supranuclear palsy, the tau protein has extra phosphate groups attached at multiple points (a process called phosphorylation); the changes to the protein cause it to fold wrongly and become tangled. The medicine is expected to work by blocking phosphorylation of tau proteins which will prevent them from folding incorrectly. In addition, it is expected that the medicine will stimulate certain cellular mechanisms (called macroautophagy) that help to clear and destroy misfolded proteins. This is expected to reduce the deterioration of brain tissue thereby improving the symptoms of the disease.

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, clinical trials with the medicine in patients with progressive supranuclear palsy were ongoing.

At the time of submission, the medicine was not authorised anywhere in the EU for progressive supranuclear palsy 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 January 2015 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.