EU/3/15/1557

On 9 October 2015, orphan designation (EU/3/15/1557) was granted by the European Commission to Desitin Arzneimittel GmbH, Germany, for sirolimus for the treatment of tuberous sclerosis.

What is tuberous sclerosis?

Tuberous sclerosis is a genetic disease that causes growth of benign tumours in different organs of the body, including the brain, lungs, heart, kidneys, skin and eyes. The symptoms and severity of the disease vary greatly from patient to patient. Depending on where the tumours are located, symptoms may include epilepsy, learning difficulties, skin abnormalities and kidney problems.

Tuberous sclerosis is a long-term debilitating disease that can be life threatening in patients with severe symptoms, who may develop severe learning disability, uncontrollable seizures (fits) and kidney failure.

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

At the time of designation, tuberous sclerosis affected less than 1.2 in 10,000 people in the European Union (EU). This was equivalent to a total of fewer than 62,000 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 512,900,000 (Eurostat 2015).

What treatments are available?

At the time of designation, the medicine Votubia (everolimus) was authorised in the EU for the treatment of tuberous sclerosis.

The sponsor has provided sufficient information to show that sirolimus might be of significant benefit for patients with tuberous sclerosis because it will be available in a formulation to be applied onto the skin, and early studies show that it may improve the skin symptoms of the condition. 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?

Sirolimus works by blocking an enzyme called ‘mammalian target of rapamycin’ (mTOR), which has increased activity in patients with tuberous sclerosis. Since mTOR is involved in the control of cell division and the growth of blood vessels, sirolimus is expected to reduce the growth of tuberous sclerosis tumours by preventing the division of tumour cells and reducing their blood supply.

Sirolimus is already authorised in the EU for the prevention of organ rejection in patients undergoing kidney transplantation.

What is the stage of development of this medicine?

The sponsor has provided data in experimental models from the published literature to support its application for orphan designation.

At the time of submission of the application for orphan designation, no clinical trials with this medicine in patients with tuberous sclerosis were ongoing.

At the time of submission, sirolimus was not authorised anywhere in the EU for tuberous sclerosis. Orphan designation of the medicine had been granted in the United States for this condition.

In accordance with Regulation (EC) No 141/2000 of 16 December 1999, the COMP adopted a positive opinion on 3 September 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.

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