EU/3/17/1910: Orphan designation for the treatment of tuberous sclerosis

Tuberous sclerosis is a genetic disease that causes growth of benign (non-cancerous) 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.

At the time of designation, tuberous sclerosis 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 is based on the information provided by the sponsor and the 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 28), Norway, Iceland and Liechtenstein. This represents a population of 515,700,000 (Eurostat 2017).

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 early studies show that the medicine, which is to be applied to the skin, has an improved formulation compared with similar products made in hospital pharmacies and may have greater benefit. This assumption will need to be confirmed at the time of marketing authorisation, in order to maintain the orphan status.

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 applied to the skin is expected to reduce the growth of skin tumours associated with tuberous sclerosis.

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

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

At the time of submission of the application for orphan designation, clinical trials with the medicine in patients with tuberous sclerosis were ongoing.

At the time of submission, the medicine was not authorised anywhere in the EU for tuberous sclerosis. Orphan designation of the medicine had been granted in the EU and 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 13 July 2017 recommending the granting of this designation.

• 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.