EU/3/19/2203: Orphan designation for the treatment of Netherton syndrome

Netherton syndrome is an inherited skin condition in which the patient, usually a newborn baby, has red, scaly skin, which cannot properly protect against infection or retain heat, water and proteins. Many babies also have a 'bamboo-type' hair structure, with strands of varying diameter. Babies born with the syndrome may fail to thrive in their first years of life and die due to infections.

Netherton syndrome is caused by a change in the gene responsible for producing a protein called LEKT1, which regulates the action of enzymes called kallikreins. Kallikreins are involved in the shedding of the skin. As a result of the change in the LEKT1 gene, kallikreins become overactive, causing excessive shedding and damage to the skin.

Netherton syndrome is a long-term debilitating and life-threatening condition because of the skin damage and associated infections, and failure to thrive.

At the time of designation, Netherton syndrome 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 28), Norway, Iceland and Liechtenstein. This represents a population of 518,400,000 (Eurostat 2019).

At the time of submission for orphan designation, no satisfactory methods were authorised in the EU for the treatment of Netherton syndrome. To reduce the inflammation of the skin in patients with Netherton syndrome, creams containing medicines such as steroids and calcineurin inhibitors were used in addition to general moisturisers and emollients (substances that soften or smooth the skin). For severe forms of the disease, medicines injected in a vein to reduce inflammation were also used.

The medicine blocks the action of a group of enzymes called serine proteases, which include kallikreins. By blocking kallikerins, the medicine, which is expected to be applied on the skin, is thought to reduce excessive shedding and damage to the skin.

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 Netherton syndrome were ongoing.

At the time of submission, the medicine was not authorised anywhere in the EU for the treatment of Netherton syndrome or designated as an orphan medicinal product elsewhere for this condition.

In accordance with Regulation (EC) No 141/2000, the COMP adopted a positive opinion on 12 September 2019, 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.