EU/3/17/1948 - orphan designation for treatment of familial cerebral cavernous malformations

4-hydroxy-2,2,6,6-tetramethylpiperidine-N-oxyl

Overview

On 12 December 2017, orphan designation (EU/3/17/1948) was granted by the European Commission to Premier Research Group Limited, United Kingdom, for 4-hydroxy-2,2,6,6-tetramethylpiperidine-N-oxyl (also known as Tempol) for the treatment of familial cerebral cavernous malformation.

 

What is familial cerebral cavernous malformation?

Familial cerebral cavernous malformation is a condition in which patients have clusters of enlarged, abnormal blood vessels in the brain that can cause symptoms such as seizures (fits), headache, weakness of arms or legs, impaired vision, and problems with memory and attention.

The condition is caused by mutations (changes) in certain genes that control the way that blood vessels grow. As a result, patients have blood vessels with thin, fragile walls that leak blood and damage surrounding brain tissue.

Familial cerebral cavernous malformation is a debilitating condition that is long lasting and may be life threatening due to severe bleeding inside the brain.

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

At the time of designation, familial cerebral cavernous malformation affected not more than 3 in 10,000 people in the European Union (EU). This was equivalent to a total of not more than 155,000 people¹, 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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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).

What treatments are available?

At the time of application, no satisfactory methods were authorised in the EU for the treatment of familial cerebral cavernous malformation. Patients were given treatment as required for symptoms such as seizures. Patients with certain symptoms had surgery to remove the abnormal blood vessels.

How is this medicine expected to work?

This medicine is expected to work by reducing oxidative stress, which is thought to be involved in the formation of clusters of abnormal blood vessels. Oxidative stress is when high levels of certain highly reactive molecules in the body damage cells and tissues. By reducing the activity of these molecules, the medicine is expected to reduce the formation of abnormal vessels and thereby improve symptoms of patients with familial cerebral cavernous malformation.

What is the stage of development of this medicine?

The effects of the medicine have been evaluated in experimental models.

At the time of submission of the application for orphan designation, no clinical trials with the medicine in patients with familial cerebral cavernous malformation had been started.

At the time of submission, the medicine was not authorised anywhere in the EU for familial cerebral cavernous malformation. Orphan designation had been granted in the United States for cerebral cavernous malformation.

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.

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/3/17/1948: Public summary of opinion on orphan designation: 4-hydroxy-2,2,6,6-tetramethylpiperidine-N-oxyl for the treatment of familial cerebral cavernous malformation

Reference Number: EMA/754098/2017

Key facts

• Active substance:
  4-hydroxy-2,2,6,6-tetramethylpiperidine-N-oxyl
• Intended use:
  Treatment of familial cerebral cavernous malformations
• Orphan designation status:
  Positive
• EU designation number:
  EU/3/17/1948
• Date of designation:
  12/12/2017
• Sponsor:

  Propharma Group The Netherlands B.V.;

Review of designation

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