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.
For a list of the administrative updates to this public summary of opinion please refer to the PDF document below.
- 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 was 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. At the time of designation, this represented a population of 506,300,000 (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 and in Switzerland for this condition.
In accordance with Regulation (EC) No 141/2000 of 16 December 1999, the COMP adopted a positive opinion on 6 May 2010 recommending the granting of this designation.
Update: Everolimus (Votubia) was authorised in the EU on 2 September 2011 for the treatment of patients aged three years and older with subependymal giant-cell astrocytoma (SEGA) associated with tuberous-sclerosis complex (TSC) who require therapeutic intervention but are not amenable to surgery. The evidence is based on analysis of change in SEGA volume. Further clinical benefit, such as improvement in disease-related symptoms, has not been demonstrated.
- 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.
|Name||Language||First published||Last updated|
|EU/3/10/764: Public summary of opinion on orphan designation of everolimus for the treatment of tuberous sclerosis||(English only)||10/08/2010||09/02/2015|
|Disease/condition||Treatment of tuberous sclerosis|
|Date of decision||04/08/2010|
|Orphan decision number||EU/3/10/764|
Review of designation
During its meeting of 8-9 June 2011, the Committee for Orphan Medicinal Products (COMP) reviewed the designation EU/3/10/764 for Votubia (everolimus) as an orphan medicinal product for the treatment of tuberous sclerosis.
The COMP assessed whether, at the time of marketing authorisation, the medicinal product still met the criteria for orphan designation. The Committee looked at the seriousness and prevalence of the condition, and the existence of other satisfactory methods of treatment. The COMP recommended that the orphan designation of the medicine be maintained.
- Life-threatening or long-term debilitating nature of the condition
The Committee for Medicinal Products for Human Use (CHMP) recommended the authorisation of Votubia for ‘the treatment of patients aged threee years and older with subependymal giant-cell astrocytoma (SEGA) associated with tuberous-sclerosis complex (TSC) who require therapeutic intervention but are not amenable to surgery’.
This falls within the scope of the product’s designated orphan indication, which is ‘treatment of tuberous sclerosis’.
The COMP concluded that there had been no change in the seriousness of the condition since the orphan designation in 2010. Tuberous sclerosis remains a condition that is debilitating in the long term and life-threatening, particularly due to the formation of multiple tumours and severe neurodevelopmental symptoms.
- Prevalence of the condition
On the basis of the information provided by the sponsor and the knowledge of the COMP, the COMP concluded that the prevalence of tuberous sclerosis remains below the ceiling for orphan designation, which is 5 people in 10,000. At the time of the review of the orphan designation, the prevalence was still estimated to be approximately 1 person in 10,000. This is equivalent to a total of around 51,000 people in the EU.
- Existence of other satisfactory methods of treatment
The COMP noted that, at the time of the review of the orphan designation, no satisfactory treatments were authorised in the EU for patients affected by this condition.
Based on the data submitted and the scientific discussion within the COMP, the COMP considered that Votubia still meets the criteria for designation as an orphan medicinal product and that Votubia should remain in the Community register of orphan medicinal products.
|Name||Language||First published||Last updated|
|Recommendation for maintenance of orphan designation at the time of addition of new indications to the marketing authorisation: Votubia (everolimus) for the treatment of tuberous sclerosis||(English only)||10/10/2011|
Sponsor’s contact details
Novartis Europharm Limited
Frimley Business Park
Camberley GU16 7SR
Tel. +41 61 324 11 11 (Switzerland)
For contact details of patients’ organisations whose activities are targeted at rare diseases, see:
- Orphanet, a database containing information on rare diseases which includes a directory of patients’ organisations registered in Europe;
- European Organisation for Rare Diseases (EURORDIS), a non-governmental alliance of patient organisations and individuals active in the field of rare diseases.