EU/3/09/712 - orphan designation for treatment of Netherton syndrome

recombinant kallikrein inhibitor

Overview

On 29 January 2010, orphan designation (EU/3/09/712) was granted by the European Commission to Voisin Consulting S.A.R.L., France, for recombinant kallikrein inhibitor for the treatment of Netherton syndrome.

The sponsorship was transferred to Dermadis S.A.S., France, in January 2012.

What is Netherton syndrome?

Netherton syndrome is an inherited skin disease. Babies born with the syndrome have red and scaly skin, which can easily get infected, and they fail to thrive in their first years of life. They also have abnormal 'bamboo-type' hair.

Netherton syndrome is caused by a genetic abnormality in one chromosome that is responsible for the production of an enzyme called LEKTI, which controls the activity of 'kallikreins'.

Kallikreins are involved in skin 'desquamation', the process through which the surface of the skin gets regularly renewed. Too much kallikrein leads to the skin problems seen in Netherton syndrome.

Netherton syndrome is a long-term debilitating and life-threatening condition because of the skin infections it is associated with, the changes to the physical appearance of the patients and their effects on the patients' mental state.

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 is equivalent to a total of around 2,500 people, and is below the threshold for orphan designation, which is 5 people in 10,000. This is based on the information provided by the sponsor and 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 504,800,000 (Eurostat 2009).

What treatments are available?

At the time of submission for orphan designation, there were no medicines authorised in the EU for the treatment of Netherton syndrome; however, one medicine was authorised for the treatment of severe congenital ichthyosis (a group of genetic skin diseases that cause dry, thickened and scaly skin). Other treatment methods include the application of emollients (substances that soften or smooth the skin) and steroids (anti-inflammatory medicines) on the skin.

The sponsor has provided sufficient information to show that recombinant kallikrein inhibitor might be of significant benefit for patients with Netherton syndrome because it may improve the treatment of patients by restoring control over the activity of kallikreins. This assumption will need to be confirmed at the time of marketing authorisation, in order to maintain the orphan status.

How is this medicine expected to work?

Recombinant kallikrein inhibitor is a copy of a natural enzyme, alpha1-antichymotrypsin, that has been slightly modified to make it able to block the activity of kallikreins. The product is expected to be applied directly to the skin of patients, where it will replace the enzyme LEKTI, which is not working in patients with Netherton syndrome. This is expected to help provide the means of controlling kallikreins and to relieve the skin symptoms associated with the syndrome.

What is the stage of development of this medicine?

The effects of recombinant kallikrein inhibitor have been evaluated in experimental models.

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

At the time of submission, recombinant kallikrein inhibitor 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 5 November 2009 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 Community) 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/3/09/712: Public summary of opinion on orphan designation of recombinant kallikrein inhibitor for the treatment of Netherton syndrome

Adopted Reference Number: EMA/744660/2009 Rev.2

Key facts

• Active substance:
  recombinant kallikrein inhibitor
• Intended use:
  Treatment of Netherton syndrome
• Orphan designation status:
  Positive
• EU designation number:
  EU/3/09/712
• Date of designation:
  29/01/2010
• Sponsor:

  Dermadis S.A.S.; Technopole d’Archamps; Bâtiment Le Forum II; 74160 Archamps; France; Telephone: + 33 4 50 43 25 26; [e-mail]