EU/3/12/956

Pemphigus is a group of autoimmune diseases characterised by widespread blistering and erosion of the skin and mucous membranes (the linings of internal organs). 'Autoimmune' means that the disease is caused by the immune system attacking the body's own cells.

In pemphigus, the autoimmune response results in damage to desmoglein, a protein which acts as a 'glue' attaching together the cells of the epidermis (the outer layer of the skin). This causes skin cells to separate from each other, causing blisters that turn into sores. In some cases these blisters can cover large areas of the skin.

Pemphigus is a long-term debilitating and life-threatening disease because of the long-term blistering which can lead to dehydration and infection.

At the time of designation, pemphigus affected approximately 2.4 in 10,000 people in the European Union (EU)*. This is equivalent to a total of around 122,000 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 27), Norway, Iceland and Liechtenstein. This represents a population of 506,300,000 (Eurostat 2011).

At the time of designation, prednisolone (a steroid) and azathioprine (a medicine that reduces the activity of the immune system) were authorised in the EU to treat pemphigus.

The sponsor has provided sufficient information to show that human monoclonal antibody against Fas ligand might be of significant benefit for patients with pemphigus because early studies show that it may be able to help prevent the blistering and skin damage seen in this condition. This assumption will need to be confirmed at the time of marketing authorisation, in order to maintain the orphan status.

This medicine is a monoclonal antibody (a type of protein) that has been designed to recognise and attach to a naturally occurring protein called 'human Fas ligand'. Skin cells release this protein when they are 'attacked' by a defective immune system. People with pemphigus have high levels of Fas ligand, which is believed to result in damage to desmoglein. By attaching to Fas ligand, this medicine is expected to prevent its action, thereby reducing the blistering seen in people with this condition.

The effects of human monoclonal antibody against Fas ligand have been evaluated in experimental models.

At the time of submission of the application for orphan designation, no clinical trials with this medicine in patients with pemphigus had been started.

At the time of submission, this medicine was not authorised anywhere in the EU for pemphigus 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 7 December 2011 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.