tuberous sclerosis - European Medicines Agency - Rare disease designations - EU/3/10/764

On 4 August 2010, orphan designation (EU/3/10/764) was granted by the European Commission to Novartis Europharm Limited, United Kingdom, for everolimus 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 mental retardation, uncontrollable seizures and kidney failure.

What is the estimated number of patients affected by the condition?
At the time of designation, tuberous sclerosis affected approximately 1 in 10,000 people in the European Union (EU)*. This is equivalent to a total of around 51,000 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 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 27), Norway, Iceland and Liechtenstein. This represents a population of 506,500,000 (Eurostat 2010).

What treatments are available?
At the time of designation, no satisfactory methods were authorised in the EU for the treatment of tuberous sclerosis. Patients were mainly treated with surgery to remove the benign tumours in the affected organs. Different treatments to control the symptoms of the disease were also used, such as antiepileptic medicines, and some patients needed a lung or kidney transplant.

How is this medicine expected to work?
Patients with tuberous sclerosis have abnormalities in the TSC1 or TSC2 genes. These genes help to regulate cell growth and division by indirectly controlling the activity of a protein called ‘mammalian target of rapamycin’ (mTOR). Abnormalities in the TSC1 or TSC2 genes result in loss of the ability to regulate mTOR in affected cells, causing uncontrolled cell growth.
Everolimus acts directly on mTOR by blocking its activity. In tuberous sclerosis, this is expected to help regulate cell division and reduce the number or size of the benign tumours that cause the symptoms of the disease.

What is the stage of development of this medicine?
The effects of everolimus have been evaluated in experimental models.
At the time of submission of the application for orphan designation, clinical trials with everolimus in patients with tuberous sclerosis were ongoing.
Everolimus was first authorised for the prevention of organ transplant rejection in several countries inside and outside the EU. It has also received authorisation for the treatment of advanced renal cell carcinoma (kidney cancer that has started to spread) in the EU and in several countries worldwide.
At the time of submission, everolimus was not authorised anywhere in the EU for tuberous sclerosis. Orphan designation of everolimus had been granted in the United States of America and in Switzerland for this condition.
In accordance with Regulation (EC)No141/2000-of 16 December 1999, the COMP adopted a positive opinion on 6 May 2010 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.
Public


EU/3/10/764: Public summary of opinion on orphan designation of Everolimus for the treatment of tuberous sclerosis (English)
http://www.ema.europa.eu/docs/en_GB/document_library/Orphan_designation/2010/08/WC500095727.pdf

European Medicines Agency - Rare disease designations - EU/3/10/764