EU/3/06/424

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Orphan designation

On 29 January 2007, orphan designation (EU/3/06/424) was granted by the European Commission to Adienne S.r.l, Italy, to thiotepa for the conditioning treatment prior to haematopoietic progenitor cell transplantation.

In January 2014, ADIENNE S.r.l. changed name to ADIENNE S.r.l.S.U.

For a list of the administrative updates to this public summary of opinion please refer to the PDF document below.

What is conditioning treatment prior to haematopoietic progenitor cell transplantation?

The term of “progenitor cell” is used to indicate those cells which are still immature, and do not express all the characteristics of the future mature cells which will derive from them. Haematopoietic progenitor cells are able to produce the cells of the blood (white blood cells, red blood cells), including the cells of the immune system and of the bone marrow. In some diseases it is necessary to give powerful drugs, which also destroy the haematopoietic progenitor cells in the bone marrow; these bone marrow cells then need to be replaced. In other diseases, the bone marrow or the immune system are absent, or working abnormally. In all these cases, it is sometimes appropriate to use a treatment called “haematopoietic progenitor cell transplantation”. This consists in replacing the abnormal cells of the immune system and the bone marrow of the patient by introducing new progenitor cells, generally from another person. Before the transplantation can take place, any existing bone marrow cells have to be eliminated from the patient. This is called “preparation” treatment or “conditioning” treatment. Diseases requiring such transplantation are life-threatening.

What is the estimated number of patients affected by the condition?

At the time of designation, conditioning treatment prior to haematopoietic progenitor cell transplantation affected approximately 0.6 in 10,000 people in the European Union (EU). This was equivalent to a total of around 30,000 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 500,300,000 (Eurostat 2007).

What treatments are available?

Available conditioning treatments are based on the use of chemotherapy (using drugs to destroy the cells) or radiotherapy (exposing the whole body to radiation to kill the cancer cells). Several treatments were authorised for the condition in the Community at the time of submission of the application for orphan drug designation. Thiotepa used in combination with other drugs might be of potential significant benefit for the conditioning treatment. This assumption will have to be confirmed at the time of marketing authorisation. This will be necessary to maintain the orphan status.

How is this medicine expected to work?

Thiotepa belongs to a group of medicines called alkylating agents. Alkylating agents are highly reactive chemicals that bind to substances in the cell, and can damage or kill the cells. It is thought that by using this mechanism, thiotepa could destroy the patient bone marrow before the transplantation of the new haematopoietic progenitor cells.

What is the stage of development of this medicine?

At the time of submission of the application for orphan designation, the effects of thiotepa had not been evaluated in experimental models. No clinical trials in patients with conditioning treatment prior to haematopoietic progenitor cell transplantation had been initiated.

Thiotepa was not authorised anywhere in the world for conditioning treatment prior to haematopoietic progenitor cell transplantation or designated as orphan medicinal product elsewhere for this condition, at the time of submission.

In accordance with Regulation (EC) No 141/2000 of 16 December 1999, the COMP adopted a positive opinion on 6 December 2006 recommending the granting of this designation.

Update: Thiotepa (Tepadina) has been authorised in the EU since 15 March 2010. Tepadina is indicated, in combination with other chemotherapy medicinal products:

  • with or without total body irradiation (TBI), as conditioning treatment prior to allogeneic or autologous haematopoietic progenitor cell transplantation (HPCT) in haematological diseases in adult and paediatric patients;
  • when high dose chemotherapy with HPCT support is appropriate for the treatment of solid tumours in adult and paediatric patients.
Opinions on orphan medicinal products designations are based on the following cumulative criteria:
  • the seriousness of the condition,
  • the existence of alternative methods of diagnosis, prevention or treatment and
  • either the rarity of the condition (affecting not more than 5 in 10,000 people in the European Union) 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>Thiotepa</p>
Active substanceThiotepa
Medicine NameTepadina
Disease/conditionConditioning treatment prior to haematopoietic progenitor cell transplantation
Date of decision29/01/2007
OutcomePositive
Orphan decision numberEU/3/06/424

Review of designation

During its meeting of 5-6 January 2010, the Committee for Orphan Medicinal Products (COMP) reviewed the designation EU/3/06/424 for Tepadina (thiotepa) as an orphan medicinal product for the conditioning treatment prior to haematopoietic progenitor cell transplantation. 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. As other satisfactory methods of treatment for patients with this condition are authorised in the European Union (EU), the COMP also looked at the significant benefit of the product over existing treatments. The COMP recommended that the orphan designation of the medicine be maintained*.

* The 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 Tepadina for use:

‘in combination with other chemotherapy medicinal products:

1) with or without total body irradiation (TBI), as conditioning treatment prior to allogeneic or autologous haematopoietic progenitor cell transplantation (HPCT) in haematological diseases in adult and paediatric patients;

2) when high dose chemotherapy with HPCT support is appropriate for the treatment of solid tumours in adult and paediatric patients’.

This falls within the scope of the product’s designated orphan indication, which is: ‘conditioning treatment prior to haematopoietic progenitor cell transplantation’.

The COMP concluded that there had been no change in the seriousness of the condition since the orphan designation in 2007. Haematopoietic progenitor cell transplantation, a treatment procedure which is performed in diseases such as acute lymphoblastic leukaemia, myelogenous leukaemia, myelodysplatic syndromes, malignant lymphomas, multiple myelomas and aplastic anaemia, is life threatening due to the underlying primary diseases and the complications that can occur during transplantation.

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 number of patients who undergo conditioning treatment prior to haematopoietic progenitor cell transplantation remains below the threshold 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 0.6 people in 10,000. This is equivalent to a total of around 30,000 people in the EU.

Existence of other satisfactory methods of treatment

At the time of the review of the orphan designation, other treatments were authorised in the EU for the conditioning treatment prior to haematopoietic progenitor cell transplantation. This included the orphan medicine Busilvex.

Significant benefit over existing treatments

Overall, the COMP concluded that the claim of a significant benefit of Tepadina as a conditioning treatment prior to haematopoietic progenitor cell transplantation is justified on the basis of a clinically relevant advantage. This is supported by the fact that Tepadina has a different safety profile to currently authorised treatments. Products for conditioning treatment are known to have serious adverse effects, and the Committee therefore considered that an alternative treatment with a different safety profile would be of significant benefit to patients.

The Committee also considered that the product might be used in combination with existing treatments, to improve the overall outcome of patients with this condition.

In conclusion, although other satisfactory methods for the treatment of this condition have been authorised in the EU, the COMP concluded that Tepadina is of significant benefit for patients undergoing conditioning treatment prior to haematopoietic progenitor cell transplantation.

Conclusions

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

Related information

Sponsor’s contact details:

ADIENNE S.r.l.S.U.
Via Galileo Galilei, 19
20867 Caponago (MB)
Italy
Tel. +39 02 4070 0445
Fax +39 02 9574 5179
E-mail: adienne@adienne.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.