On 21 June 2011, orphan designation (EU/3/11/879) was granted by the European Commission to United Therapeutics Europe Ltd, United Kingdom, for chimeric monoclonal antibody against GD2 for the treatment of neuroblastoma.
Update: chimeric monoclonal antibody against GD2, dinutuximab (Unituxin) has been authorised in the EU since 14 August 2015 for the treatment of high-risk neuroblastoma in patients aged 12 months to 17 years, who have previously received induction chemotherapy and achieved at least a partial response, followed by myeloablative therapy and autologous stem cell transplantation (ASCT). It is administered in combination with granulocyte-macrophage colony-stimulating factor (GM-CSF), interleukin-2 (IL-2), and isotretinoin.
- What is neuroblastoma?
Neuroblastoma is a cancer of nerve cells which is usually seen as a lump in the abdomen (belly area) or around the spine. Symptoms may include weakness, bone pain, loss of appetite and fever. Neuroblastoma is the most common solid tumour outside the brain in children. In many cases it is present at birth but is diagnosed later when the cancer has spread to other parts of the body and the child begins to show symptoms of the disease.
Neuroblastoma is a life-threatening disease that is associated with poor long-term survival.
- What is the estimated number of patients affected by the condition?
At the time of designation, neuroblastoma affected approximately 1.1 in 10,000 people in the European Union (EU)*. This is equivalent to a total of around 56,000 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 27), Norway, Iceland and Liechtenstein. This represents a population of 506,300,000 (Eurostat 2011).
- What treatments are available?
At the time of designation, several medicines were authorised for the treatment of neuroblastoma in the EU. Treatments for neuroblastoma included surgery, radiotherapy (treatment with radiation) and chemotherapy (medicines to treat cancer).
The sponsor has provided sufficient information to show that chimeric monoclonal antibody against GD2 might be of significant benefit for patients with neuroblastoma because it works in a different way to existing treatments, and early studies show that it might improve the outcome of patients with this 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?
Chimeric monoclonal antibody against GD2 is a monoclonal antibody (a type of protein) that has been designed to recognise and attach to a specific structure (an antigen) called GD2. GD2 is a substance that is present in high amounts on the surface of neuroblastoma cells, but not normal cells. The way this medicine works is not fully understood, but studies have shown that in the presence of certain cells or proteins of the body’s defence system, the neuroblastoma cells to which the medicine is attached die.
- What is the stage of development of this medicine?
The effects of chimeric monoclonal antibody against GD2 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 neuroblastoma were ongoing.
At the time of submission, the medicine was not authorised anywhere in the EU for neuroblastoma. Orphan designation of this medicine had been granted in the United States of America for this condition.
In accordance with Regulation (EC) No 141/2000 of 16 December 1999, the COMP adopted a positive opinion on 7 April 2011 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.
|Name||Language||First published||Last updated|
|EU/3/11/879: Public summary of opinion on orphan designation: Chimeric monoclonal antibody against GD2 for the treatment of neuroblastoma||(English only)||12/07/2011|
|Active substance||Chimeric monoclonal antibody against GD2|
|Disease/condition||Treatment of neuroblastoma|
|Date of decision||21/06/2011|
|Orphan decision number||EU/3/11/879|
Review of designation
During its meeting of 16 to 18 June 2015, the Committee for Orphan Medicinal Products (COMP) reviewed the designation EU/3/11/879 for Unituxin (dinutuximab) for the treatment of neuroblastoma. 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 methods of treatment. As other methods of treatment are authorised in the European Union (EU), the COMP also considered whether the medicine is of significant benefit to patients with neuroblastoma. The COMP recommended that the orphan designation of the medicine be maintained1.
1The maintenance of the orphan designation at time of marketing authorisation would, except in specific situations, give an orphan medicinal product 10 years of market exclusivity in the EU. This means that in the 10 years after its authorisation similar products with a comparable therapeutic indication cannot be placed on the market.
- Life-threatening or long-term debilitating nature of the condition
The Committee for Medicinal Products for Human Use (CHMP) recommended the authorisation of Unituxin for:
‘the treatment of high-risk neuroblastoma in patients aged 12 months to 17 years, who have previously received induction chemotherapy and achieved at least a partial response, followed by myeloablative therapy and autologous stem cell transplantation (ASCT). It is administered in combination with granulocyte-macrophage colony-stimulating factor (GM-CSF), interleukin-2 (IL-2), and isotretinoin.’
This indication falls within the scope of the product’s designated orphan indication, which is: ‘treatment of neuroblastoma’.
The COMP concluded that there had been no change in the seriousness of the condition since the orphan designation in 2011. Neuroblastoma remains a condition that is debilitating in the long term and associated with poor overall survival.
- Prevalence of the condition
The sponsor performed a search of the scientific literature and concluded that no publications are available which suggest a change in prevalence of neuroblastoma.
On the basis of the information provided by the sponsor and the knowledge of the COMP, the COMP concluded that the prevalence of neuroblastoma 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 1.1 people in 10,000. This is equivalent to a total of around 56,000 people in the EU.
- Existence of other methods of treatment
At the time of the review of the orphan designation, other treatments were authorised in the EU for the treatment of neuroblastoma. Treatments included surgery, radiotherapy (treatment with radiation), chemotherapy (medicines to treat cancer) and blood stem-cell transplantation.
- Significant benefit of Unituxin
The claim of a significant benefit of Unituxin is based on data showing that the use of Unituxin in maintenance treatment improves survival in previously treated patients with high-risk neuroblastoma. Therefore, although other methods for the treatment of neuroblastoma have been authorised in the EU, the COMP concluded that Unituxin is of significant benefit to patients affected by this condition.
Based on the data submitted and the scientific discussion within the COMP, the COMP considered that Unituxin still meets the criteria for designation as an orphan medicinal product and that Unituxin 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 marketing authorisation: Unituxin (dinutuximab) for the treatment of neuroblastoma||(English only)||08/09/2015|
Sponsor’s contact details
United Therapeutics Europe Ltd
Curfew Bell Road
Surrey KT16 9FG
Tel. +44 (0)1932 573800
Fax +44 (0)1932 571110
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.