EU/3/17/1951: Orphan designation for the treatment of pemphigus

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 (the body's natural defences) attacking the body's own cells.

In pemphigus, the immune system produces antibodies that attack desmoglein, a protein which acts as a 'glue' attaching the cells of the epidermis (the outer layer of the skin). As a result skin cells 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 1.4 in 10,000 people in the European Union (EU). This was equivalent to a total of around 72,000 people¹, 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).

¹Disclaimer: 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 515,700,000 (Eurostat 2017).

At the time of designation, prednisolone (a corticosteroid) 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 this medicine might be of significant benefit for patients with pemphigus because early studies show that it may reduce the need for corticosteroids in some patients. This assumption will need to be confirmed at the time of marketing authorisation, in order to maintain the orphan status.

This medicine reduces the activity of an enzyme known as Bruton tyrosine kinase (BTK). This enzyme activates certain immune cells including those involved in pemphigus. By reducing BTK's activity, this medicine is expected to reduce the autoimmune response in patients with pemphigus, thus improving the symptoms of the disease.

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 pemphigus were ongoing.

At the time of submission, the medicine was not authorised anywhere in the EU for pemphigus. Orphan designation of the medicine had been granted in the United Stated for this condition.

In accordance with Regulation (EC) No 141/2000 of 16 December 1999, the COMP adopted a positive opinion on 31 October 2017 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.