EU/3/14/1419

On 15 January 2015, orphan designation (EU/3/14/1419) was granted by the European Commission to Dr Yanick Crow, France, for tenofovir disoproxil fumarate for the treatment of Aicardi-Goutières syndrome.

What is Aicardi-Goutières syndrome?

Aicardi-Goutières syndrome is a hereditary disorder that mainly affects the brain and skin. Most patients do not have symptoms at birth, but develop symptoms within the first year of life, such as irritability and feeding difficulties, and sometimes seizures (fits). Most children with Aicardi-Goutieres syndrome have severe intellectual disability, and around 40% have painful, itchy skin lesions, usually on the fingers, toes and ears.

Aicardi-Goutières syndrome is a long-term debilitating and life-threatening disease due to the severe brain dysfunction, which in most cases results in death during childhood.

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

At the time of designation, Aicardi-Goutières syndrome affected approximately 1 in 10,000 people in the European Union (EU). This was equivalent to a total of around 51,000 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 511,100,000 (Eurostat 2014).

What treatments are available?

At the time of designation, no satisfactory methods were authorised in the EU for the treatment of Aicardi-Goutières syndrome. Patients received symptomatic treatment such as managing feeding problems and, if present, epilepsy.

How is this medicine expected to work?

Aicardi-Goutières syndrome is caused by mutations (defects) in any of 7 genes that are responsible for making certain enzymes which break up unneeded molecules of DNA. As a result, unneeded molecules of DNA accumulate inside cells. These DNA molecules are mistaken by the body’s immune system for those of viruses, triggering an immune response against the body’s own DNA that results in severe brain dysfunction and the other symptoms of Aicardi-Goutières syndrome.

Tenofovir disoproxil fumarate is a type of antiviral medicine, called a ‘nucleotide reverse transcriptase inhibitor’ and already authorised for the treatment of human immunodeficiency (HIV-1). In the body, tenofovir disoproxil fumarate is converted to its active form, tenofovir. Tenovofir is expected to work in Aicardi-Goutières syndrome by blocking an enzyme called ‘reverse transcriptase’ that is involved in the production of some types of unneeded DNA molecules, thereby decreasing their accumulation within cells. This is expected to prevent the triggering of an immune response against the body own DNA, thus improving the symptoms of Aicardi-Goutières syndrome.

What is the stage of development of this medicine?

The effects of tenofovir disoproxil fumarate 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 Aicardi-Goutières syndrome had been started.

Tenofovir has been authorised worldwide for many years for the treatment of HIV-1 infections. At the time of submission, tenofovir disoproxil fumarate was not authorised anywhere in the EU for Aicardi-Goutières 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 11 December 2014 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.

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