EU/3/12/1062

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Orphan designation

On 8 November 2012, orphan designation (EU/3/12/1062) was granted by the European Commission to Apeiron Biologics AG, Austria, for chimeric monoclonal antibody against GD2 for the treatment of neuroblastoma.

This medicine is now known as dinutuximab beta.

Chimeric monoclonal antibody against GD2 has been authorised in the EU as Dinutuximab beta Apeiron since 8 May 2017.

What is neuroblastoma?

Neuroblastoma is a cancer of nerve cells which is usually seen as a lump in the abdomen 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 long-term debilitating and 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 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 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 in the EU for the treatment of neuroblastoma. Treatments for neuroblastoma included surgery, chemotherapy (medicines to treat cancer) and radiotherapy (treatment with radiation).

The sponsor has provided sufficient information to show that the medicine might be of significant benefit for patients with neuroblastoma because it works in a different way to existing medicines 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. 

When the medicine attaches to the neuroblastoma cells, it marks them out as a target for the body’s immune system, which is then expected to attack the cancer cells and thereby reverse or slow down the progression of the disease.

What is the stage of development of this medicine?

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 neuroblastoma were ongoing.

At the time of submission, the medicine was not authorised anywhere in the EU for neuroblastoma. Orphan designation has 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 5 October 2012 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.

Key facts

Product details for <p>Chimeric monoclonal antibody against GD2</p>
Active substanceChimeric monoclonal antibody against GD2
Medicine NameDinutuximab beta Apeiron
Disease/conditionTreatment of neuroblastoma
Date of decision08/11/2012
OutcomePositive
Orphan decision numberEU/3/12/1062

Review of designation

On 18 April 2017, the Committee for Orphan Medicinal Products (COMP) completed its review of the designation EU/3/12/1062 for Dinutuximab beta Apeiron (dinutuximab beta, previously known as chimeric monoclonal antibody against GD2) as an orphan medicinal product 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 maintained.1


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 the same 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 Dinutuximab beta Apeiron for ‘treatment of high-risk neuroblastoma in patients aged 12 months and above, who have previously received induction chemotherapy and achieved at least a partial response, followed by myeloablative therapy and stem cell transplantation, as well as patients with history of relapsed or refractory neuroblastoma, with or without residual disease’.

This falls within the scope of the product’s designated orphan indication, which is ‘neuroblastoma’.

The COMP concluded that there had been no change in the seriousness of the condition since the orphan designation in 2012. Neuroblastoma remains a debilitating condition and is life-threatening when the cancer spreads to other parts of the body.

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 57,000 people in the EU.

Existence of other methods of treatment

At the time of the review of the orphan designation, several chemotherapy medicines were authorised in the EU for the treatment of neuroblastoma, including cyclophosphamide, doxorubicin, melphalan and vincristine. Treatments for neuroblastoma also included surgery, radiotherapy (treatment with radiation), and haematopoietic stem cell transplantation (a transplant of blood-producing cells).

Significant benefit of Dinutuximab beta Apeiron

The COMP concluded that the claim of a significant benefit of Dinutuximab beta Apeiron in neuroblastoma is justified because in studies the medicine improved survival in neuroblastoma patients whose cancer did not improve or came back after other cancer treatments.

Therefore, although other methods for the treatment of this condition have been authorised in the EU, the COMP concluded that Dinutuximab beta Apeiron is of significant benefit to patients affected by neuroblastoma.

Conclusions

Based on the data submitted and the scientific discussion within the COMP, the COMP considered that Dinutuximab beta Apeiron still meets the criteria for designation as an orphan medicinal product and that it should remain in the Community Register of Orphan Medicinal Products.

More information on the COMP assessment can be found in the March 2017 COMP minutes.

Further information on Dinutuximab beta Apeiron can be found in the European public assessment report (EPAR) on the Agency’s website.

Related information

Sponsor’s contact details:

Apeiron Biologics AG
Campus-Vienna-Biocenter 5
1030 Vienna
Austria
Tel. +43 1 8656577 115
Fax +43 1 8656577 800
E-mail: apeiron@apeiron-biologics.com

Patients' organisations:

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.