EU/3/15/1454 - orphan designation for treatment of Netherton syndrome

6-ethoxy-7-methoxy-2-(2-methylsulfanylphenyl)-3,1-benzoxazin-4-one

Overview

On 19 March 2015, orphan designation (EU/3/15/1454) was granted by the European Commission to Sixera Pharma AB, Sweden, for 6-ethoxy-7-methoxy-2-(2-methylsulfanylphenyl)-3,1-benzoxazin-4-one for the treatment of Netherton syndrome.

What is Netherton syndrome?

Netherton syndrome is an inherited skin condition in which the patient, usually a new born 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.

Netherton syndrome is caused by a mutation (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 mutation 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.

What is the estimated number of patients affected by the condition?

At the time of designation, Netherton syndrome affected approximately 0.05 in 10,000 people in the European Union (EU). This was equivalent to a total of around 2,600 people*, and is below the ceiling for orphan designation, which is 5 people in 10,000. This isbased on the information provided by the sponsor and the knowledge of the Committee for Orphan Medicinal Products (COMP).

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*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 512,900,000 (Eurostat 2015).

What treatments are available?

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).

How is this medicine expected to work?

The medicine is a molecule that blocks the effect of kallikreins. It is expected that when applied to the skin in patients with Netherton syndrome it will block the excess kallikrein activity and so allow the skin to function more normally, relieving the symptoms of the condition.

What is the stage of development of this medicine?

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

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

At the time of submission, the medicine was not authorised anywhere in the EU for Netherton syndrome 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 12 February 2015 recommending the granting of this designation.

Opinions on orphan medicinal product designations are based on the following three criteria:

• 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.

EU/3/15/1454: Public summary of positive opinion for orphan designation of 6-ethoxy-7-methoxy-2-(2-methylsulfanylphenyl)-3,1-benzoxazin-4-one for the treatment of Netherton syndrome

AdoptedReference Number: EMA/COMP/116731/2015

Key facts

• Active substance:
  6-ethoxy-7-methoxy-2-(2-methylsulfanylphenyl)-3,1-benzoxazin-4-one
• Intended use:
  Treatment of Netherton syndrome
• Orphan designation status:
  Positive
• EU designation number:
  EU/3/15/1454
• Date of designation:
  19/03/2015
• Sponsor:

  Sixera Pharma AB; c/o GU Holding AB; Erik Dahlbergsgatan 11a 2t; 411 26 Göteborg; Västra Götaland; Sweden; Tel. [phone] (Spain); E-mail: [e-mail]

Review of designation

The Committee for Orphan Medicinal Products reviews the orphan designation of a product if it is approved for marketing authorisation.