EU/3/16/1659: Orphan designation for the treatment of inclusion body myositis

Inclusion body myositis is a condition in which muscle cells become damaged and inflamed, leading to progressive muscle weakness in the legs and arms and difficulty in walking and swallowing. The disease mainly affects people over 50 and is more common in men than in women.

Inclusion body myositis is a long-term debilitating condition due to the development of disabling muscle weakness and problems with swallowing.

At the time of designation, inclusion body myositis affected approximately 0.05 in 10,000 people in the European Union (EU). This was equivalent to a total of around 2,500 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 the treatment of inclusion body myositis. Patients were often given treatment to suppress the immune system although the benefit was unclear. Supportive measures included physical therapy and exercise, and the use of devices and aids to mobility including motorised wheelchairs.

The mechanisms that lead to the disease are not well understood, but seem to include abnormalities in the way that proteins in muscle cells are folded, leading them to become tangled and clump together inside cells. Arimoclomol is a medicine that stimulates the cell's natural mechanisms for coping with damage, by activating a class of proteins called 'heat shock proteins' in cells that are under stress. Heat shock proteins aid the correct folding of damaged proteins. By activating these proteins in muscle cells that are at risk of damage, the medicine is expected to reduce protein misfolding and so improve muscle weakness and other symptoms of the disease.

The effects of arimoclomol citrate 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 inclusion body myositis were ongoing.

At the time of submission, arimoclomol citrate was not authorised anywhere in the EU for inclusion body myositis. Orphan designation of the medicine had been granted in the EU and the United States for two other conditions associated with muscle weakness and difficulty moving, called amyotrophic lateral sclerosis and Niemann-Pick disease, type C.

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