EU/3/08/596

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Orphan designation

On 15 January 2009, orphan designation (EU/3/08/596) was granted by the European Commission to Seattle Genetics UK Limited, United Kingdom, for monoclonal antibody against human CD30 covalently linked to the cytotoxin monomethylauristatin E for the treatment of Hodgkin lymphoma.

The sponsorship was transferred to Takeda Global Research and Development Centre (Europe) Ltd, United Kingdom, in September 2010 and subsequently to Takeda Pharma A/S, Denmark, in October 2013.

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

What is Hodgkin lymphoma?

Hodgkin’s lymphoma is a type of cancer that develops in the lymphatic system. The lymphatic system is part of the body’s immune system: the body's natural defense against infection and disease. It is a complex system made up of organs such as bone marrow (the spongy tissue inside the large bones in the body), thymus and spleen, and a network of lymph nodes throughout the body that are connected by lymphatic vessels. As lymphatic tissue is found throughout the body, Hodgkin's lymphoma can begin in almost any part of the body and can spread to almost any tissue or organ in the body. Normally, the growth and duplication of lymphatic cells takes place in a controlled manner, however in Hodgkin’s lymphoma this process is out of control and the cells continue to divide, developing into a tumour. Hodgkin's lymphoma can occur in both adults and children; however, treatment for adults may be different from treatment for children. Hodgkin's lymphoma can usually be cured, if found and treated early. Despite the available treatments Hodgkin’s lymphoma remains a serious and life threatening condition in certain patients.

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

At the time of designation, Hodgkin lymphoma affected approximately 1 in 10,000 people in the European Union (EU). This was equivalent to a total of around 50,000 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 504,800,000 (Eurostat 2009).

What treatments are available?

Three different types of standard treatment are available and used: chemotherapy (using drugs to kill cancer cells), radiotherapy (using high-energy x-rays or other types of high-energy rays to kill cancer cells) and surgery (removing all possible cancer tissue in an operation). Bone marrow transplantation is also used. Several treatments had been authorized at the time of submission of the application for orphan drug designation.

The monoclonal antibody against CD30 covalently linked to the cytotoxin monomethylauristatin E could be of significant benefit for the treatment of Hodgkin’s lymphoma. The main reasons are that it may offer a new way of targeting and killing cancer cells and it might improve the long-term outcome of the patients. 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?

CD30 is a molecule that Hodgkin lymphoma cells have on their surface (surface marker). One part of the medicinal product is an antibody against CD30 (anti-CD30), therefore is able to recognise and bind to CD30. The antibody is linked to a small molecule called monomethyl auristatin E, which is cytotoxic (kills rapidly dividing cancer cells). The CD30 antibody part of the product acts as a carrier for the cytotoxic substance. The product is thought to bind specifically on CD30 receptor of the lymphoma cells. Once bound on the cell surface, it is taken up by the cells. Once inside the cancer cells, the cytotoxic molecule, monomethyl auristatin E, gets released and stops cell division. The cancer cells are then expected to undergo programmed cell death.

What is the stage of development of this medicine?

The effects of monoclonal antibody against human CD30 covalently linked to the cytotoxin monomethylauristatin E have been evaluated in experimental models.

At the time of submission of the application for orphan designation, no clinical trials in patients with Hodgkin’s lymphoma had been started.

At the time of submission, the antibody against human CD30 covalently linked to the cytotoxin monomethylauristatin E was not authorised anywhere in the world for Hodgkin lymphoma or designated as orphan medicinal product elsewhere for this condition.

In accordance with Regulation (EC) No 141/2000 of 16 December 1999, the COMP adopted a positive opinion on 8 October 2008 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;
  • and either the rarity of the condition (affecting not more than five in 10,000 people in the Community) or the 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 the quality, safety and efficacy is necessary before a product can be granted a marketing authorisation.

Key facts

Product details for <p>Monoclonal antibody against human CD30 covalently linked to the cytotoxin monomethylauristatin E</p>
Active substanceMonoclonal antibody against human CD30 covalently linked to the cytotoxin monomethylauristatin E
Medicine NameAdcetris
Disease/conditionTreatment of Hodgkin lymphoma
Date of decision14/01/2009
OutcomePositive
Orphan decision numberEU/3/08/596

Review of designation

During its meeting of 4-5 September 2012, the Committee for Orphan Medicinal Products (COMP) reviewed the designation EU/3/08/596 for Adcetris (brentuximab vedotin1) as an orphan medicinal product for the treatment of Hodgkin lymphoma. 

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 maintained2.

1Previously known as monoclonal antibody against human CD30 covalently linked to the cytotoxin monomethylauristatin E.

2The 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 Adcetris for the treatment of:

‘relapsed or refractory CD30+ Hodgkin lymphoma (HL): following autologous stem cell transplant or following at least two prior therapies when autologous stem cell transplantation or multi-agent chemotherapy is not a treatment option’.

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

The COMP concluded that there had been no change in the seriousness of the condition since the orphan designation in 2009. Hodgkin lymphoma remains a serious and life threatening condition that is associated with poor long-term prognosis in patients whose disease has come back after previous treatment.

Prevalence of the condition

The sponsor provided updated information on the prevalence on the basis of data from the Globocan 2002 database and updated population data. On the basis of the information provided by the sponsor and the knowledge of the COMP, the Committee concluded that the prevalence of Hodgkin lymphoma 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 estimated to be approximately 1 in 10,000 people. This is equivalent to a total of around 51,000 people in the EU.

Existence of other satisfactory methods of treatment

At the time of the review of the orphan designation, several medicines were authorised for the treatment of Hodgkin lymphoma in the EU. The main treatments for Hodgkin lymphoma included chemotherapy (medicines to treat cancer) and radiotherapy (treatment with radiation). Autologous haematopoietic (blood) stem cell transplantation was also used when the disease had not responded or had come back after treatment. This is a complex procedure where patients receive their own stem cells to help them restore the bone marrow.

Significant benefit over existing treatments

The COMP concluded that the claim of a significant benefit of Adcetris over existing treatments is justified on the basis of it being more effective at improving the survival of patients who previously received other treatments and who no longer responded to them.

This is based on study data in patients who had previously received other treatments such as chemotherapy and/or stem cell transplantation. These data showed that progression-free survival (PFS, how long the patients lived without their disease getting worse) after Adcetris was longer than the actual or predicted PFS after other treatments. In addition, the prolonged survival seen with Adcetris could enable some patients to undergo further stem cell transplantation.

Therefore, although other satisfactory methods for the treatment of this condition have been authorised in the EU, the COMP concluded that Adcetris is of significant benefit for patients affected by Hodgkin lymphoma.

Conclusions

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

Sponsor’s contact details:

Takeda Pharma A/S
Langebjerg 1
4000 Roskilde
Denmark
Tel. +45 46 77 1036
Fax +45 46 75 6640

Patients’ associations contact points:

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.