EU/3/13/1130: Orphan designation for the treatment of transglutaminase-1-deficient autosomal recessive congenital ichthyosis

Transglutaminase-1-deficient autosomal recessive congenital ichthyosis is an inherited skin disorder caused by abnormalities in a gene called TGM1, which produces the enzyme transglutaminase-1. This enzyme is important for normal formation of the outer layer of the skin. The main feature of the disorder is dry, thick, scaly or flaky skin. In its most severe form, children are born prematurely and have problems such as dehydration and difficulties in maintaining a normal body temperature.

Transglutaminase-1-deficient autosomal recessive congenital ichthyosis is a long-term debilitating disease due to the appearance of symptoms at birth or in early childhood. It can cause life-threatening complications in newborn babies including breathing and feeding problems and infections.

At the time of designation, transglutaminase-1-deficient autosomal recessive congenital ichthyosis affected approximately 0.04 in 10,000 people in the European Union (EU). This was equivalent to a total of around 2,000 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 509,000,000 (Eurostat 2013).

At the time of designation, acitretin was authorised in some countries of the EU to treat autosomal recessive congenital ichthyosis. In addition, basic measures to manage patients with this condition included mechanical scale removal and moisturising of the underlying skin.

The sponsor has provided sufficient information to show that this medicine might be of significant benefit for patients with transglutaminase-1-deficient autosomal recessive congenital ichthyosis because studies in experimental models show that it helps restore a more normal structure in the skin of patients with this condition. This assumption will need to be confirmed at the time of marketing authorisation, in order to maintain the orphan status.

Patients with transglutaminase-1-deficient autosomal recessive congenital ichthyosis lack an enzyme called transglutaminase-1. This medicine is expected to be available as a cream that contains the transglutaminase-1 enzyme as its active substance. Transglutaminase-1 is contained within tiny fatty particles called liposomes, which are expected to carry the enzyme through the skin. This is expected to help restore the normal formation of the outer layer of the skin.

The transglutaminase-1 in this medicine is made by a method known as 'recombinant DNA technology': it is made by cells into which a gene (DNA) has been introduced that makes them able to produce the enzyme.

At the time of submission of the application for orphan designation, the evaluation of the effects of this medicine in experimental models was ongoing.

At the time of submission, no clinical trials with the medicine in patients with transglutaminase-1-deficient autosomal recessive congenital ichthyosis had been started.

At the time of submission, the medicine was not authorised anywhere in the EU for transglutaminase-1-deficient autosomal recessive congenital ichthyosis 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 17 April 2013 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.